Guia Prático para Oncologia SBOC 2012

Guia miolo correo_Manual Conflito.
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Tumor de Stio Primrio Desconhecido

PCE Paclitaxel: 200 mg/m2 IV D1 Carboplatina: AUC 6 IV D1 Etoposide: 50 mg alternando com 100 mg VO D1-10 a cada 21 dias Ref. (1) EP Etoposide: 80 a 120 mg/m2 IV D15 Cisplatina: 60 a 100 mg/m2 IV D1 a cada 21 dias PEB Cisplatina: 20 mg/m2 IV D15 Etoposide: 100 mg/m2 IV D15 Bleomicina: 30 unidades IV D1, 8 e 15 a cada 21 dias GC Gencitabina 1250mg/m2 IV D1 e D8 Cisplatina 100mg/m2 IV D1 a cada 21 dias IC Irinotecano 150 mg/m2 IV D1 Cisplatina 80mg/m2 IV D1 a cada 21 dias PCF Paclitaxel 200mg/m2 IV em 1 hora D1 e D22
Guia Prtico para o Oncologista Clnico
Ref. (2, 4)
Ref. (3)
Ref. (5)
Ref. (5)
Guia miolo correo_Manual Conflito.qxd 3/10/2011 15:54 Page 10
Carboplatina AUC 6 IV D1 e D22 5-Fluorouracil: 225mg/m2/dia IV em 24 horas, D1 a D35 a cada 6 semanas Ref. (6) GD Gencitabina: 1000mg/m2 IV D1 e D8 Docetaxel: 75 mg/m2 IV D8 em 1 hora a cada 21 dias DC Docetaxel: 75mg/m2 IV D1 Cisplatina: 75mg/m2 IV D1 OU Docetaxel: 60mg/m2 IV D1 Carboplatina: AUC 6 IV D1 a cada 21 dias CP Paclitaxel: 200mg/m2 IV D1 em 3 horas D1 Carboplatina: AUC 6 IV D1 a cada 21 dias GCP Gencitabina: 1000mg/m2 IV D1 e D8 Paclitaxel: 200mg/m2 IV D1 Carboplatina: AUC 6 IV D1 a cada 21 dias CAE Carboplatina: 400mg/m2 IV D1 Adriamicina: 50mg/m2 IV D1 Etoposide: 100mg/m2 IV D1 a D3 a cada 21 dias
Ref. (7)
Ref. (8)
Ref. (9)
Ref. (10)
Ref. (11)
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GC Gencitabina: 1000mg/m2 IV D1 e D8 Carboplatina: AUC 5 IV D8 a cada 21 dias GCC Carboplatina: AUC 5 IV D1 Gencitabina: 1000mg/m2 IV D1 e D8 Capecitabina: 1600mg/m2 VO D1 a D14 a cada 21 dias IC Irinotecano: 60mg/m2 IV D1,8 e 15 Carboplatina: AUC 5 IV D1 a cada 28 dias
Ref. (12)
Ref. (13)
Ref. (14)
GEMZAR Gencitabina: 1000mg/m2 D1,D8 e D15 IV a cada 28 dias Ref. (15) GI Gencitabina: 1000mg/m2 IV D1 e D8 Irinotecano: 100mg/m2 IV D1 e D8 a cada 21 dias
Ref. (16)
OC Oxaliplatina: 130mg/m2 IV D1 Capecitabina: 1000mg/m2 duas vezes ao dia VO D1 a D14 a cada 21 dias Ref. (17) GCP Cisplatina: 35mg/m2 IV D1 e D8 Gencitabina: 1000mg/m2 IV D1 e D8 Paclitaxel: 70mg/m2 IV D1 e D8 a cada 21 dias
Ref. (18)
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GCV Cisplatina: 35mg/m2 IV D1 e D8 Gencitabina: 1000mg/m2 IV D1 e D8 Vinorelbina: 25mg/m2 IV D1 e D8 a cada 21 dias
Ref. (18)
1. Hainsworth JD, Erlance JB, Kalman LA, Schreeder MT, Greco FA. Carcinoma of unknown primary site: treatment with 1hour paclitaxel, carboplatin, extended-schedule etoposide. J Clin Oncol 1997;15:23852393. 2. Longeval E, et al. Combination chemotherapy with cisplatin and etoposide in bronchogenic squamous cell carcinoma adenocarcinoma.A study by the EORTC lung cancer working party. Cancer1982;50:27512756. 3. Hainsworth JD, et al. Cisplatin-based combination chemotherapy in the treatment of poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown primary site: results of a 12-year experience. J Clin Oncol 1992;10:912922. 4. Sheperd FA. Treatment of advanced non-small cell lung cancer. Semin Oncol. 1994; 21(suppl 7): 7-18. 5. Culine S; Lortholary A; Voigt JJ; Bugat R; Theodore C; Priou F; Kaminsky MC; Lesimple T; Pivot X; Coudert B; Douillard JY; Merrouche Y; Allouache J; Goupil A; Negrier S; Viala J; Petrow P; Bouzy J; Laplanche A; Fizazi K. Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: results of a randomized phase II study--trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01). J Clin Oncol 2003 Sep 15;21(18):3479-82. 6. Hainsworth JD, Burris HA 3rd, Meluch AA, Baker MN, Morrissey LH, Greco FA. Paclitaxel, carboplatin, and longterm continuous infusion of 5-fluorouracil in the treatment of advanced squamous and other selected carcinomas: results of a Phase II trial. Cancer. 2001 Aug 1;92(3):642-9.
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7. Pouessel D; Culine S; Becht C; Ychou M; Romieu G; Fabbro M; Cupissol D; Pinguet F. Gemcitabine and docetaxel as frontline chemotherapy in patients with carcinoma of an unknown primary site. Cancer 2004 Mar 15;100(6):1257-61. 8. Carcinoma of unknown primary site: phase II trials with docetaxel plus cisplatin or carboplatin.Greco FA; Erland JB; Morrissey LH; Burris HA 3rd; Hermann RC; Steis R; Thompson D; Gray J; Hainsworth JD. Ann Oncol 2000 Feb;11(2):211-5. 9. Briasoulis E; Kalofonos H; Bafaloukos D; Samantas E; Fountzilas G; Xiros N; Skarlos D; Christodoulou C; Kosmidis P; Pavlidis Carboplatin plus paclitaxel in unknown primary carcinoma: a phase II Hellenic Cooperative Oncology Group Study. J Clin Oncol 2000 Sep;18(17):3101- 7. 10. Greco FA; Burris HA 3rd; Litchy S; Barton JH; Bradof JE; Richards P; Scullin DC Jr; Erland JB; Morrissey LH; Hainsworth JD. Gemcitabine, carboplatin, and paclitaxel for patients with carcinoma of unknown primary site: a Minnie Pearl Cancer Research Network study. J Clin Oncol 2002 Mar 15;20(6): 1651-6. 11. Piga A, Nortilli R, Cetto GL, Cardarelli N, Fedeli SL, Fiorentini G, D'Aprile M, Giorgi F, Parziale AP, Contu A, Montironi R, Gesuita R, Carle F, Cellerino R.Carboplatin, doxorubicin and etoposide in the treatment of tumours of unknown primary site. Br J Cancer. 2004 May 17;90(10):1898-904. 12. Pittman KB; Olver IN; Koczwara B; Kotasek D; Patterson WK; Keefe DM; Karapetis CS; Parnis FX; Moldovan S; Yeend SJ; Price TJ Gemcitabine and carboplatin in carcinoma of unknown primary site: a phase 2 Adelaide Cancer Trials and Education Collaborative study. Br J Cancer. 2006 Nov 20;95(10):1309-13. Epub 2006 Oct 31. 13. Schneider BJ; El-Rayes B; Muler JH; Philip PA; Kalemkerian GP; Griffith KA; Zalupski MM. Phase II trial of carboplatin, gemcitabine, and capecitabine in patients with carcinoma of unknown primary site. Cancer. 2007 Aug 15;110(4):770-5. 14. Yonemori K; Ando M; Yunokawa M; Hirata T; Kouno T; Shimizu C; Tamura K; Katsumata N; Hirakawa A; Matsumoto
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K; Yamanaka Y; Arioka H; Fujiwara Y. Irinotecan plus carboplatin for patients with carcinoma of unknown primary site. Br J Cancer. 2009 Jan 13;100(1):50-5. Epub 2008 Dec 16. 156. Hainsworth JD; Burris HA 3rd; Calvert SW; Willcutt NT; Scullin DC Jr; Bramham J; Greco FA. Gemcitabine in the second-line therapy of patients with carcinoma of unknown primary site: a phase II trial of the Minnie Pearl Cancer Research Network. Cancer Invest 2001;19(4):335-9. 16. Hainsworth JD; Spigel DR; Raefsky EL; Kuzur ME; Yost K; Kommor M; Litchy S; Greco FA. Combination chemotherapy with gemcitabine and irinotecan in patients with previously treated carcinoma of an unknown primary site: a Minnie Pearl Cancer Research Network Phase II trial. Cancer 2005 Nov 1;104(9):1992-7. 17. Hainsworth JD; Spigel DR; Burris HA 3rd; Shipley D; Farley C; Macias-Perez IM; Barton J; Greco FA. Oxaliplatin and capecitabine in the treatment of patients with recurrent or refractory carcinoma of unknown primary site: a phase 2 trial of the Sarah Cannon Oncology Research Consortium. Cancer. 2010 May 15;116(10):2448-54. 18. Palmeri S; Lorusso V; Palmeri L; Vaglica M; Porta C; Nortilli R; Ferrau F; Comella G; Massidda B; Danova M Cisplatin and gemcitabine with either vinorelbine or paclitaxel in the treatment of carcinomas of unknown primary site : results of an Italian multicenter, randomized, phase II study. Cancer. 2006 Dec 15;107(12):2898-905.
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Tumores do Sistema Nervoso Central

Temozolomida + Radioterapia Temozolomida: 75 mg/m2 VO ou IV por 6 semanas concomitante a radioterapia, seguido por 150 mg/m2 VO D15 a cada 28 dias Dose da Temozolomida aps a radioterapia: 150 a 200 mg/m2 VO D 1-5 a cada 28 dias. Ref. (1) e Ref. (9) PCV Procarbazina: 60 mg/m2 VO D821 Lomustina: 110 mg/m2 VO D1 Vincristina: 1.4 mg/m2 IV D8 e 29 a cada 6 a 8 semanas por 6 a 7 ciclos (2). BCNU BCNU: 200 mg/m2 IV D1 a cada 68 semanas por um ano Ref. (3 ,4,10) OU BCNU: 75100 mg/m2 IV D1 e 2 a cada 68 semanas
Ref. (3)
Procarbazina Procarbazina: 150 mg/m2 VO diariamente dividido em 3 doses. Ref. (5) Temozolomida Temozolomida: 150 mg/m2 VO ou IV D15 a cada 28 dias
Ref. (6)
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Irinotecano Irinotecano: 350 mg/m2 IV em 90 min D1 a cada 3 semanas
Ref. (7)
OU Irinotecano: 125 mg/m2 IV semanalmente por 4 semanas a cada 6 semanas Ref. (8) ACE Carboplatina: AUC 5 IV D1 Etoposide: 100mg/m2 IV D1 a D3 Bevacizumabe: 10mg/kg IV D2 a cada 3 semanas BCE BCNU: 200mg/m2 IV D1 Cisplatina: 20mg/m2 IV D1 a D5 Etoposide: 100mg/m2 IV D1 a D5 a cada 5 semanas, seguido por radioterapia Temozolamida + Cisplatina Temozolamida: 200 mg/m2/dia VO ou IV por 5 dias Cisplatina: 100mg/m2 IV D1 Cisplatina + Carmustina Cisplatina: 100mg/m2 IV D1 a cada 21 dias Carmustina: 160mg/m2 IV D2 a cada 42 dias
Ref. (11)
Ref. (12)
Ref. (13)
Ref. (14,15)
Temozolamida + Cisplatina Cisplatina: 75mg/m2 IV D1 Temozolamida: 150mg/m2 VO ou IV D1 a D5 a cada 21 dias Ref. (16)
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Bevacizumabe + Irinotecano Bevacizumabe: 10mg/kg IV Irinotecano: 125mg/m2 IV (se paciente no usando antiepilptico) ou 340mg/m2 IV (se paciente usando antiepiltico) a cada 15 dias Ref. (17, 18)
1. Stupp R, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352: 987995. 2. Levin VA, et al. Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, evincristine (PCV) over BCNU poranaplastic gliomas: NCOG 6G61 final report. Int J Radiat Oncol Biol Phys 1990; 18:321324. 3. DeAngelis LM, et al. Malignant gliomas: who benefits from adjuvant chemotherapy? Ann Neurol 1998; 44:691695. 4. Buckner JC, et al. Phase II trial of procarbazine, lomustine, andvincristine as initial therapy porpatients with low-grade oligodendrioglioma or oligoastrocytoma: efficacy eassociations with chromosomal abnormalities. J Clin Oncol 2003; 21: 251255. 5. Yung A, et al. Randomized trial of temodal (TEM) vs. procarbazine (PCB) in glioblastoma multiforme (GBM) at first relapse. Proc Am Soc Clin Oncol 1999;18:139a. 6. Yung A, et al. Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. J Clin Oncol 1999; 17: 27622771. 7. Raymond E, et al. Multicenter phase II study and pharmacokinetic analysis of irinotecan in chemotherapynave patients with glioblastoma. Ann Oncol 2003; 14: 603614. 8. Friedman H, et al. Irinotecan therapy in adults with recurrent or progressive malignant glioma. J Clin Oncol 1999; 17: 15161525.
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9. Stupp R; Hegi ME; Mason WP; van den Bent MJ; Taphoorn MJ; Janzer RC; Ludwin SK; Allgeier A; Fisher B; Belanger K; Hau P; Brandes AA; Gijtenbeek J; Marosi C; Vecht CJ; Mokhtari K; Wesseling P; Villa S; Eisenhauer E; Gorlia T; Weller M; Lacombe D; Cairncross JG; Mirimanoff. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTCNCIC trial. Lancet Oncol. 2009 Mar 6. 10. Stewart LA . Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet 2002 Mar 23; 359(9311):1011-8. 11. Francesconi AB, Dupre S, Matos M, Martin D, Hughes BG, Wyld DK, Lickliter JD. .Carboplatin and etoposide combined with bevacizumab for the treatment of recurrent glioblastoma multiforme. J Clin Neurosci. 2010 Aug; 17(8): 970-4. 12. Lassen U, Kristjansen PE, Wagner A, Kosteljanetz M, Poulsen HS. Treatment of newly diagnosed glioblastoma multiforme with carmustine, cisplatin and etoposide followed by radiotherapy. A phase II study. J Neurooncol. 1999 Jun; 43(2):161-6. 13. Balaa C, Lpez-Pousa A, Berrocal A, Yaya-Tur R, Herrero A, Garca JL, Martn-Broto J, Benavides M, Cerd-Nicols M, Ballester R, Balart J, Capellades J.Phase II study of temozolomide and cisplatin as primary treatment prior to radiotherapy in newly diagnosed glioblastoma multiforme patients with measurable disease. A study of the Spanish Medical Neuro-Oncology Group (GENOM). J Neurooncol. 2004 Dec;70(3):359-69. 14. Buckner JC, Ballman KV, Michalak JC, Burton GV, Cascino TL, Schomberg PJ, Hawkins RB, Scheithauer BW, Sandler HM, Marks RS, O'Fallon JR; North Central Cancer Treatment Group 93-72-52; Southwest Oncology Group 9503 Trials Phase III trial of carmustine and cisplatin compared with
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carmustine alone and standard radiation therapy or accelerated radiation therapy in patients with glioblastoma multiforme: North Central Cancer Treatment Group 93-7252 and Southwest Oncology Group 9503 Trials. J Clin Oncol. 2006 Aug 20;24(24):3871-9. 15. Silvani A, Gaviani P, Lamperti EA, Eoli M, Falcone C, Dimeco F, Milanesi IM, Erbetta A, Boiardi A, Fariselli L, Salmaggi A. Cisplatinum and BCNU chemotherapy in primary glioblastoma patients. J Neurooncol. 2009 Aug;94(1): 57-62. Epub 2009 Feb 11. 16. Zustovich F, Lombardi G, Della Puppa A, Rotilio A, Scienza R, Pastorelli D. A phase II study of cisplatin and temozolomide in heavily pre-treated patients with temozolomiderefractory high-grade malignant glioma. Anticancer Res. 2009 Oct; 29(10): 4275-9. 17. Vredenburgh JJ, Desjardins A, Herndon JE 2nd, Marcello J, Reardon DA, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Sampson J, Wagner M, Bailey L, Bigner DD, Friedman AH, Friedman HS. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol. 2007 Oct 20; 25(30): 4722-9. 18. Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, Park J, Albert PS, Fine HA. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009 Feb 10;27(5):7405. Epub 2008 Dec 29.
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Tumores Neuroendcrinos
Adriamicina + Estreptozotocina Adriamicina: 50 mg/m2 IV D1 e 22 Estreptozotocina: 500 mg/m2/dia IV D15 cada 6 semanas
Ref. (1)
EP Cisplatina: 45 mg/m2/dia IV por infuso contnua D2 e D3 Etoposide: 130 mg/m2/dia IV por infuso contnua nos D1-3 a cada 21 dias Ref. (2) EP Etoposide: 100 mg/m2 IV D1-3 Cisplatina: 25 mg/m2 IV D1-3 a cada 21 dias
Ref. (3)
Carboplatina + radioterapia Carboplatina: AUC 2, semanal, durante radioterapia Ref. (6) Octreotide Octreotide: 150250 g SC uma a trs vezes por dia Ref. (4) Octreotide LAR: 20 a 40 mg IM 1x/ms Ref. (5) 5-Fluorouracil + Octreotide 5-Fluorouracil: 200mg/m2 IV diariamente Octreotide LAR: 20mg IM mensalmente Everolimo + Octreotide Everolimo: 5 a 10mg/dia VO Octreotide LAR: 30mg/ms IM
Ref. (7)
Ref. (8)
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PCE Paclitaxel: 200mg/m2 IV em 1 hora D1 Carboplatina: AUC 6 IV D1 Etoposide VO alternando 50mg e 100mg diariamente , D1 a D10 a cada 21 dias Ref. (10) Irinotecano + Cisplatina Irinotecano: 65mg/m2 IV D1 e D8 Cisplatina: 30mg/m2 IV D1 e D8 a cada 21 dias
Ref. (11)
Temozolamida + Talidomida Temozolamida: 150mg/m2 VO por 7 dias, a cada 15 dias Talidomida: 50 a 400mg VO diariamente. Ref. (12) Etoposide e Carboplatina associado a Radioterapia Etoposide: 80mg/m2 D1 a D3 IV Carboplatina: AUC 4.5 IV Semanas 1, 4, 7 e 10 Ref. (13) FDE Fluorouracil: 500mg/m2 IV D1 a D3 Dacarbazina: 200mg/m2 IV D1 a D3 Epirrubicina: 30mg/m2 IV D1 a D3 a cada 21 dias
Ref. (14)
Interferon alpha 2a Interferon 6 x 106 UI diariamente x 8 semanas, seguido por 6 x 106 UI , trs vezes por semana Ref. (15) Everolimo 10 mg VO dia uso contnuo
Ref. (16)
1. Moertel CG, et al. Streptozocin-Adriamicina, streptozocinfluorouracil,or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med 1992;326:519526.
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2. Moertel CG, et al. Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin. Cancer 1991; 68:227232. 3. Longeval E, et al. Combination chemotherapy with cisplatin and etoposide in bronchogenic squamous cell carcinoma adenocarcinoma.A study by the EORTC lung cancer working party. Cancer. 1982; 50:27512756. 4. Saltz L, et al. Octreotide as an antineoplastic agent in the treatmentof functional and nonfunctional neuroendocrine tumors. Cancer 1993;72:244. 5. Rubin J. et al Octreotide Acetate Long-Acting Formulation Versus Open-Label Subcutaneous Octreotide Acetate in Malignant Carcinoid Syndrome. J Clin Oncol 17:600, 1999. 6. Poulsen M, Walpole E, Harvey J, Dickie G, O'Brien P, Keller J, Tripcony L, Rischin D. Weekly carboplatin reduces toxicity during synchronous chemoradiotherapy for Merkel cell carcinoma of skin. Int J Radiat Oncol Biol Phys. 2008 Nov 15;72(4):1070-4. 7. Brizzi MP, Berruti A, Ferrero A, Milanesi E, Volante M, Castiglione F, Birocco N, Bombaci S, Perroni D, Ferretti B, Alabiso O, Ciuffreda L, Bertetto O, Papotti M, Dogliotti L. Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte oncology network. BMC Cancer. 2009 Nov 3;9:388. 8. Yao JC, Phan AT, Chang DZ, Wolff RA, Hess K, Gupta S, Jacobs C, Mares JE, Landgraf AN, Rashid A, Meric-Bernstam F. Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study J Clin Oncol. 2008 Sep 10;26(26):4311-8. ERRATUM J Clin Oncol. 2008 Dec 1; 26 (34) 5660. 10. Hainsworth JD, Spigel DR, Litchy S, Greco FA. Phase II trial of paclitaxel, carboplatin, and etoposide in advanced poorly differentiated neuroendocrine carcinoma: a Minnie Pearl Cancer Research Network Study. J Clin Oncol. 2006 Aug 1; 24(22):3548-54.
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11. Kulke MH, Wu B, Ryan DP, Enzinger PC, Zhu AX, Clark JW, Earle CC, Michelini A, Fuchs CS. A phase II trial of irinotecan and cisplatin in patients with metastatic neuroendocrine tumors. Dig Dis Sci, 2006 Jun;51(6): 1033-8. 12. Kulke MH, Stuart K, Enzinger PC, Ryan DP, Clark JW, Muzikansky A, Vincitore M, Michelini A, Fuchs CS. Phase II study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors. J Clin Oncol. 2006 Jan 20;24(3):401-6. 13. Poulsen M, Rischin D, Walpole E, Harvey J, Mackintosh J, Ainslie J, Hamilton C, Keller J, Tripcony L; Trans-Tasman Radiation Oncology Group High-risk Merkel cell carcinoma of the skin treated with synchronous carboplatin/etoposide and radiation: a Trans-Tasman Radiation Oncology Group Study--TROG 96:07. J Clin Oncol. 2003 Dec 1;21(23):4371-6. 14. Bajetta E, Rimassa L, Carnaghi C, Seregni E, Ferrari L, Di Bartolomeo M, Regalia E, Cassata A, Procopio G, Mariani L. 5Fluorouracil, dacarbazine, and epirubicin in the treatment of patients with neuroendocrine tumors. Cancer. 1998 Jul 15; 83(2):372-8. 15. Bajetta E, Zilembo N, Di Bartolomeo M, Di Leo A, Pilotti S, Bochicchio AM, Castellani R, Buzzoni R, Celio L, Dogliotti L, et al. Treatment of metastatic carcinoids and other neuroendocrine tumors with recombinant interferonalpha-2a. A study by the Italian Trials in Medical Oncology Group. Cancer. 1993 Nov 15;72(10):3099-105. 16. Yao, James C. M.D.; Shah, Manisha H. M.D.; Ito, Tetsuhide M.D. et. al. Everolimus for Advanced Pancreatic Neuroendocrine Tumors. N Engl J Med. 2011; 364 (6): 514523.
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Cncer Anal
5-Fluorouracil + Mitomicina C 5-Fluorouracil: 1,000 mg/m2/dia IV por infuso contnua D14 e D2932 concomitante a radioterapia Mitomicina C: 15 mg/m2 IV no D1 Ref. (1) 5-Fluorouracil + Mitomicina C 5-Fluorouracil: 750 mg/m2/dia IV infuso contnua D1-5 e D2933, concomitante a radioterapia Mitomicina C: 15 mg/m2 IV no D1 Ref. (2) 5-Fluorouracil + Cisplatina 5-Fluorouracil: 1,000 mg/m2/dia IV infuso contnua nos D1 a 5 Cisplatina: 75 mg/m2 IV D2 Ref. (3) Capecitabina + Mitomicina C Capecitabina: 825mg/m2 VO BID durante os dias da radioterapia Mitomicina C: 12mg/m2 IV D1 Ref. (4)
1. Nigro ND, et al. Combined preoperative radiation and chemotherapy for squamous cell carcinoma of the anal canal. Cancer 1983;51:18261829. 2. Bartelink H, et al. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization por Research e Treatment of
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Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol 1997;15:20402049. 3. Hung A, et al. Cisplatin-based combined modality therapy for anal carcinoma: a wider therapeutic index. Cancer 2003; 97:11951202. 4. Glynne-Jones R; Meadows H; Wan S; Gollins S; Leslie M; Levine E; McDonald AC; Myint S; Samuel L; SebagMontefiore D. Multicenter Phase II Study of Chemoradiation Using a 5 Day per Week Oral Regimen of Capecitabine and Intravenous Mitomycin C in Anal Cancer. Int J Radiat Oncol Biol Phys. 2008 May 7.
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Cncer Colo-retal
5-Fluorouracil + Radioterapia 5-Fluorouracil: 1,000 mg/m2/dia IV infuso contnua D1 a 5 Repetir nas semanas 1 e 5 da radioterapia 5-Fluorouracil: 500 mg/m2 IV contnuo durante 5 dias a cada 28 dias por 4 ciclos Ref. (1) Capecitabina + Radioterapia Capecitabina: 825 mg/m2 VO BID durante toda a radioterapia OU Capecitabina: 9001,000 mg/m2 VO BID D15 de cada semana da radioterapia Ref. (2) 5-Fluorouracil + Leucovorin (Mayo Clinic) 5-Fluorouracil: 425 mg/m2 IV D5 Leucovorin: 20 mg/m2 IV D15 (administrado antes do 5Fluorouracil) a cada 28 dias Ref. (3) 5-Fluorouracil + Leucovorin (Roswell Park) 5-Fluorouracil: 500 mg/m2 IV semanalmente por 6 semanas Leucovorin: 500 mg/m2 IV em 2 horas semanalmente por 6 semanas, administrado antes do 5-Fluorouracil a cada 8 semanas Ref. (4) 5-Fluorouracil + Leucovorin 5-Fluorouracil: 500 mg/m2 IV semanalmente por 6 semanas Leucovorin: 20 mg/m2 IV semanalmente por 6 semanas, Administrado antes do 5-Fluorouracil a cada 8 semanas Ref. (5)
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Quasar 5-Fluorouracil: 370mg/m2 IV Leucovorin: 25 ou 175mg IV (dose fixa) Uma vez por semana, por 30 semanas (29, 38) FOLFOX4 Oxaliplatina: 85 mg/m2 IV D1 5-Fluorouracil: 400 mg/m2 IV pulso, seguido por 600 mg/m2 IV infuso contnua por 22 horas D1 e 2 Leucovorin: 200 mg/m2 IV D1 e 2 em uma infuso de 2 horas, antes do 5-Fluorouracil. a cada 2 semanas Ref. (6) FLOX Nrdico Oxaliplatina: 85mg/m2 IV em 2 horas D1 5-Fluorouracil: 500mg/m2 IV pulso D1 e D2 Leucovorin: 60mg/m2 IV pulso D1 e D2 Intervalo a cada 14 dias
Ref. (30)
ROX Oxaliplatina: 85mg/m2 IV 2 horas D1 e D15 Leucovorin: 250mg/m2 IV 2horas D1, 8 e15 5-Fluorouracil: 500mg/m2 IV pulso, D1, 8 e 15 a cada 4 semanas (31) Capecitabina Capecitabina: 1,250 mg/m2 VO BID D114 a cada 21 dias
Ref. (7)
Irinotecano + 5-Fluorouracil + Leucovorin (IFL) Irinotecano: 125 mg/m2 IV em 90 minutos semanalmente por 4 semanas 5-Fluorouracil: 500 mg/m2 IV semanalmente por 4 semanas Leucovorin: 20 mg/m2 IV semanalmente por 4 semanas a cada 6 semanas Ref. (8)
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Irinotecano + 5-Fluorouracil + Leucovorin (IFL) + Bevacizumabe (BV) Irinotecano: 125 mg/m2 IV em 90 minutos semanalmente por 4 semanas (D1, 8, 15, 22) 5-Fluorouracil: 500 mg/m2 IV semanalmente por 4 semanas (D1, 8, 15, 22) Leucovorin: 20 mg/m2 IV semanalmente por 4 semanas (D1, 8,15, 22) Bevacizumabe: 5 mg/kg IV a cada 2 semanas D1,15 a cada 6 semanas Ref. (9) IFL (Regime de Douillard) Irinotecano: 180 mg/m2 IV D1 5-Fluorouracil: 400 mg/m2 IV pulso, seguido por 600 mg/m2 IV infuso contnua por 22 horas D1 e 2 Leucovorin: 200 mg/m2 IV D1 e 2 em 2 horas (infundir antes do 5-Fluorouracil) a cada 2 semanas Ref. (11) FOLFIRI Irinotecano: 180 mg/m2 IV D1 5-Fluorouracil: 400 mg/m2 IV pulso D1, seguido por 2.400 mg/m2 IV infuso contnua por 46 horas. Leucovorin: 200 mg/m2 IV D1 em 2 horas (infundir antes do 5Fluorouracil) a cada 2 semanas Ref. (12) FOLFOX6 Oxaliplatina: 100 mg/m2 IV D1 5-Fluorouracil: 400 mg/m2 IV pulso D1, seguido por 2.400 mg/m2 IV por infuso contnua em 46 horas. Leucovorin: 400 mg/m2 IV D1 em 2 horas (infundir antes do 5Fluorouracil) a cada 2 semanas Ref. (13)
28
m FOLFOX6 Oxaliplatina: 85 mg/m2 IV em 2 horas D1 Leucovorin: 350 mg/m2 IV em 2 horas D1 5-Fluorouracil: 400 mg/m2 IV pulso D1, seguido por 2.400 mg/m2 IV em infuso contnua de 46 horas. a cada 2 semanas por 12 ciclos Ref. (39) FOLFOX7 Oxaliplatina: 130 mg/m2 IV D1 5-Fluorouracil: 2.400 mg/m2 IV infuso contnua D1 e 2 por 46 horas. Leucovorin: 400 mg/m2 IV D1 em 2 horas (infundir antes do 5Fluorouracil) a cada 2 semanas Ref. (13) FOLFOXIRI Irinotecano: 150mg/m2 IV D1 Oxaliplatina: 65mg/m2 IV D2 Leucovorin: 200mg/m2 IV D2 e D3 5-Fluorouracil: 400mg/m2 IV pulso D2 e D3 5-Fluorouracil: 600mg/m2 IV em infuo contnua D2 e D3 a cada 15 dias Ref. (32) Cetuximabe + Irinotecano Cetuximabe: 400 mg/m2 IV dose de ataque, seguido de 250 mg/m2 IV semanalmente Irinotecano: 350 mg/m2 IV D1 a cada 21 dias Ref. (14) XELOX Capecitabina + Oxaliplatina Capecitabina: 1,000 mg/m2 VO BID D114 Oxaliplatina: 130 mg/m2 IV D1 a cada 21 dias
29
Capecitabina: 1.750 mg/m2 VO BID D17 Oxaliplatina: 85 mg/m2 IV D1 a cada 14 dias XELIRI Capecitabina: 1.000 mg/m2 VO BID D114 Irinotecano: 250 mg/m2 IV D1 a cada 21 dias IROX Oxaliplatina + Irinotecano Oxaliplatina: 85 mg/m2 IV D1 Irinotecano: 200 mg/m2 IV D1 a cada 3 semanas Raltitrexede + Oxaliplatina Raltitrexede: 2,5mg/m2 IV em 15 minutos D1 Oxaliplatina: 100mg/m2 IV em 180 minutos D1 a cada 3 semanas Raltitrexede: 3mg/m2 IV D1 Mitomicina C: 6mg/m2 IV D1 a cada 4 semanas OU Raltitrexede: 3mg/m2 IV D1 a cada 3 semanas Mitomicina C: 7mg/m2 IV D1 a cada 6 semanas OU Raltitrexede: 3mg/m2 IV D1 Mitomicina C: 7mg/m2 IV D1 a cada 3 a 4 semanas
Ref. (15)
Ref. (16)
Ref. (17)
Ref. (33)
Ref. (34)
Ref. (35)
Ref. (28)
30
5-Fluorouracil + Leucovorin + Bevacizumabe 5-Fluorouracil: 500 mg/m2 IV semanalmente por 6 semanas Leucovorin: 500 mg/m2 IV semanalmente por 6 semanas, Administrado antes do 5-Fluorouracil Bevacizumabe: 5 mg/kg IV a cada 2 semanas a cada 8 semanas Ref. (18) de Gramont Regimen 5-Fluorouracil: 400 mg/m2 IV seguido de 600 mg/m2 IV por 22 horas D1 e D2 Leucovorin: 200 mg/m2 IV D1 e 2 em infuso de 2 horas a cada 2 semanas Ref. (19) FOLFOX4 + Bevacizumabe Oxaliplatina: 85 mg/m2 IV D1 5-Fluorouracil: 400 mg/m2 IV pulso, seguido por 600 mg/m2 IV por infuso contnua D1 e D2 Leucovorin: 200 mg/m2 IV D1 e 2 em infuso de 2 horas antes do 5-Fluorouracil Bevacizumabe: 10 mg/kg IV a cada 2 semanas a cada 2 semanas Ref. (20) Capecitabina + Oxaliplatina (XELOX) + Bevacizumabe Capecitabina: 850 mg/m2 VO BID D114 Oxaliplatina: 130 mg/m2 IV D1 Bevacizumabe: 7.5 mg/kg a cada 3 semanas a cada 21 dias Ref. (21) FLOX Oxaliplatina: 85mg/m2 IV em duas horas D1,15,29 Leucovorin: 500mg/m2 IV D1, 8, 15, 22, 29, 36 5-Fluorouracil: 500mg/m2 IV D1, 8, 15, 22, 29, 36 a cada 8 semanas por 3 ciclos
Ref. (27)
31
Capecitabina Capecitabina: 1.250 mg/m2 VO BID D114 a cada 21 dias
Ref. (22)
Irinotecano (CPT11) (semanal) Irinotecano: 125 mg/m2 IV em 90 minutos semanalmente por 4 semanas. a cada 6 semanas Ref. (23) Irinotecano: 125 mg/m2 IV em 90 minutos semanalmente por 2 semanas. A cada 3 semanas. Irinotecano: 175 mg/m2 IV D1 e 10 a cada 3 semanas Irinotecano: 350 mg/m2 IV D1 a cada 3 semanas
Ref. (24)
Ref. (25)
Cetuximabe Cetuximabe: 400 mg/m2 IV dose de ataque, seguido por 250 mg/m2 IV semanalmente Ref. (26) Cetuximabe + Irinotecano Irinotecano: 180mg/m2 IV D1 Cetuximabe: 500mg/m2 IV D1 a cada 15 dias b-Fol Oxaliplatina: 85mg/m2 D1 e 15 Leucovorin: 20mg/m2 D1, 8 e 15 5-Fluorouracil: 500mg/m2 D1, 8 e 15 a cada 28 dias Ref. (40)
Ref. (36, 37)
32
UFT Leucovorin: 90 mg/dia VO D1 a D28 2 UFT: 100 mg/m trs vezes ao dia VO D1 a D28 a cada 35 dias Ref. (41) FOLFIRI com bevacizumabe Irinotecano:180 mg/m2 IV D1 Leucovorin: 200 mg/m2 IV D1 2 5-Fluorouracil: 400 mg/m IV pulso D1 2 5-Fluorouracil: 2400 mg/m IV em infuso de 46 horas D1 Bevacizumabe: 5 mg/kg IV D1 a cada 14 dias Ref. (42)
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metastatic colorectal cancer. J Clin Oncol 2004;22:2330. 18. Kabbinavar F, et al. Results of a randomized phase II controlled trial of bevacizumab in combination with 5fluorouracil eleucovorin as first-line therapy in subjects with metastatic CRC. Proc Am Soc Clin Oncol 2004;23:Abstract 3516. 19. de Gramont A, et al. Randomized trial comparing monthly lowdose leucovorin efluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French Intergroup study. J Clin Oncol 1997;15:808815. 20. Mitchell EP, et al. High-dose bevacizumab in combination with FOLFOX4 improves survival in patients with previously treated advanced colorectal cancer: results from the Eastern Cooperative Oncology Group (ECOG) study E3200. Presented at the 2005 American Society of Clinical Oncology Gastrointestinal Cancers Symposium; January 2729, 2005 Hollywood, FL (abstract 169a). 21. Hochster HS, et al. Bevacizumab (B) with oxaliplatin (O)based chemotherapy in the first-line therapy of metastatic colorectal cancer (mCRC): Preliminary results of the randomized TREE-2 trial. Presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium; January 2729, 2005 Hollywood, FL (abstract 241). 22. Hoff P, et al. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol 2001;15:22822292. 23. Pitot HC, et al. Phase II trial of irinotecan in patients with metastatic colorectal carcinoma. J Clin Oncol 1997; 15: 29102919. 24. Ulrich-Pur H, et al. Multicenter phase II trial of dosefractionated irinotecan in patients with advanced colorectal cancer failing oxaliplatin- based first-line combination chemotherapy. Ann Oncol 2001; 12:12691272.
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25. Rougier P, et al. Phase II study of irinotecan in the treatment of advanced colorectal cancer in chemotherapy-nave patients and patients pretreated with fluorouracil-based chemotherapy. J Clin Oncol 1997;15:251260. 26. Saltz LB, et al. Phase II trial of cetuximab in patients with refractory colorectal cancer that expressed the epidermal growth factor receptor. J Clin Oncol 2004;22:12011208. 27. Kuebler JP et al: Oxaliplatin combined with weekly bolus of fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C07. J Clin Oncol. 2007; 25:2198-2204. 28. Murad AM, Aragao BC, Guimares RC. Phase II Trial of the Use of Raltitrexed and Mitomycin-C in the Treatment of Advanced Colorectal Cancer after 5FU Failure: Final Results. Proc Am Soc Clin Oncol, 2001 (20) abst 2188. 29. D. J. Kerr, R. Gray, C. McConkey & J. Barnwell for the QUASAR Colorectal Cancer Study Group. Adjuvant chemotherapy with 5-fluorouracil, L-folinic acid and levamisole for patients with colorectal cancer: Non-randomised comparison of weekly versus four-weekly schedules - less pain, same gain. Ann Oncol (2000) 11 (8): 947-955. 30. Srbye H, Glimelius B, Berglund A, Fokstuen T, Tveit KM, Braendengen M, greid D, Dahl O. Multicenter phase II study of Nordic fluorouracil and folinic acid bolus schedule combined with oxaliplatin as first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2004 Jan 1; 22(1): 31-8. 31. Yamada Y, Ohtsu A, Boku N, Miyata Y, Shimada Y, Doi T, Muro K, Muto M, Hamaguchi T, Mera K, Yano T, Tanigawara Y, Shirao K. Phase I/II study of oxaliplatin with weekly bolus fluorouracil and high-dose leucovorin (ROX) as first-line therapy for patients with colorectal cancer. Jpn J Clin Oncol. 2006 Apr; 36(4):218-23. 32. Souglakos J, Androulakis N, Syrigos K, Polyzos A, Ziras N, Athanasiadis A, Kakolyris S, Tsousis S, Kouroussis Ch, Vamvakas L, Kalykaki A, Samonis G, Mavroudis D,
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Georgoulias V. FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG). Br J Cancer. 2006 Mar 27; 94(6):798-805. 33. Cortinovis D, Bajetta E, Di Bartolomeo M, Dognini G, Beretta E, Ferrario E, Ricotta R, Buzzoni R. Raltitrexed plus oxaliplatin in the treatment of metastatic colorectal cancer. Tumori. 2004 Mar-Apr; 90(2):186-91. 34. Rosati G, Rossi A, Germano D, Reggiardo G, Manzione L. Raltitrexed and mitomycin-C as third-line chemotherapy for colorectal cancer after combination regimens including 5fluorouracil, irinotecan and oxaliplatin: a phase II study. Anticancer Res. 2003 May-Jun; 23(3C):2981-5. 35. Michels J, Geldart T, Darby A, Craddock L, Iveson A, Richardson L, Iveson T. The combination of raltitrexed (Tomudex) and mitomycin-C in the treatment of advanced colorectal cancer - a phase II study. Clin Oncol (R Coll Radiol). 2006 Aug;18(6):431-5. 36. P Martn-Martorell1, S Rosello 1, E Rodrguez-Braun1, I Chirivella1, A Bosch1 and A Cervantes Biweekly cetuximab and irinotecan in advanced colorectal cancer patients progressing after at least one previous line of chemotherapy: results of a phase II single institution trial British Journal of Cancer (2008) 99, 455458. 37. Pfeiffer P., D. Nielsen, J. Bjerregaard, C. Qvortrup, M. Yilmaz & B. Jensen. Biweekly cetuximab and irinotecan as third-line therapy in patients with advanced colorectal cancer after failure to irinotecan, oxaliplatin and 5-fluorouracil Annals of Oncology 19: 11411145, 2008 38. Gray R, Barnwell J, McConkey C et al. Quasar Collaborative Group. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet. 2007 Dec 15;370(9604):2020-9.
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39. Hochster HS, Hart LL, et al. Safety and Efficacy of Oxaliplatin and Fluoropyrimidine Regimens With or Without Bevacizumab as First-Line Treatment of Metastatic Colorectal Cancer: Results of the TREE Study. J Clin Oncol; 2008:26:3523-3529. 40. H. S. Hochster, A. Chachoua, J. Speyer, et al. Oxaliplatin with weekly bolus 5FU and low-dose leucovorin (bFOL) as firstline therapy of colorectal cancer; a phase II study. 41. Lembersky BC, et al. Oral Uracil and Tegafur Plus Leucovorin Compared With Intravenous Fluorouracil and Leucovorin in Stage II and III Carcinoma of the Colon: Results From National Surgical Adjuvant Breast and Bowel Project Protocol C-06. J Clin Oncol 2006;24:2059-64. 42. Kopetz SM, et al., Preliminary results from a phase II study of infusional 5-FU, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for metastatic colorectal cancer (mCRC), ASCO Annual Meeting Proceedings Part I, J Clin Oncol, 2006; 24, No 18S (Supplement): (Abstract 3579).
38
Cncer de Intestino Delgado

CAPOX Oxaliplatina: 130mg/m2 IV D1 Capecitabina: 750mg/m2 VO BID D1 a D14 FAM 5-Fluorouracil: 600mg/m2 IV D1,8,29 e 36. Doxorrubicina: 30mg/m2 IV D1 e D29 Mitomicina C: 10mg/m2 IV D1 Irinotecano + Cisplatina Irinotecano: 70mg/m2 IV D1 e D15 Cisplatina: 80mg/m2 IV D1 a cada 28 dias Ref. (1)
Ref. (2)
Ref. (5)
FOLFOX Oxaliplatina: 85 ou 100 ou 135mg/m2 IV em 2 horas D1 Leucovorin: 400mg/m2 IV em 2 horas D1 5-Fluorouracil: 400mg/m2 IV em pulso D1 5-Fluorouracil: 2400mg/m2 IV em 48 horas, infuso contnua a cada 15 dias Ref. (3, 4) FOLFIRI Irinotecano: 180mg/m2 IV em 90 minutos D1 Leucovorin: 400mg/m2 IV em 2 horas D1 5-Fluorouracil: 400mg/m2 IV em pulso D1 5-Fluorouracil: 2400mg/m2 IV em 48 horas, infuso contnua a cada 15 dias Ref. (4, 5)
1. Overman MJ, Varadhachary GR, Kopetz S, Adinin R, Lin E, Morris JS, Eng C, Abbruzzese JL, Wolff RA. Phase II study of
39
capecitabine and oxaliplatin for advanced adenocarcinoma of the small bowel and ampulla of Vater. J Clin Oncol. 2009 Jun 1;27(16):2598-603. 2. Gibson MK, Holcroft CA, Kvols LK, Haller D. Phase II study of 5-fluorouracil, doxorubicin, and mitomycin C for metastatic small bowel adenocarcinoma. Oncologist. 2005;10(2):132-7. 3. Overman MJ, Kopetz S, Wen S, Hoff PM, Fogelman D, Morris J, Abbruzzese JL, Ajani JA, Wolff RA. Chemotherapy with 5fluorouracil and a platinum compound improves outcomes in metastatic small bowel adenocarcinoma. Cancer. 2008; 113(8):2038-45. 4. Kocher C, Malka D, Boige V, Lebray P, Elias D, Lasser P, Ducreux M. Combination chemotherapy in advanced small bowel adenocarcinoma. Oncology. 2005;69(4):290-4. 5. Fishman PN, Pond GR, Moore MJ, Oza A, Burkes RL, Siu LL, Feld R, Gallinger S, Greig P, Knox JJ. Natural history and chemotherapy effectiveness for advanced adenocarcinoma of the small bowel: a retrospective review of 113 cases. Am J Clin Oncol. 2006;29(3):225-31.
40
Cncer de Esfago
5-Fluorouracil + Cisplatina + Radioterapia 5-Fluorouracil: 1.000 mg/m2/dia IV infuso contnua D1 a D4 Cisplatina: 75 mg/m2 IV no D1 Repetir nas semanas 1, 5, 8, e 11 Ref. (1) 5-Fluorouracil + Cisplatina + Radioterapia (Esquema Hopkins/Yale) 5-Fluorouracil: 225 mg/m2/dia IV infuso contnua D1 a D30 Cisplatina: 20 mg/m2/dia IV D15 e 2630 Paclitaxel: 135 mg/m2 IV em 24 horas D1 Cisplatina: 75 mg/m2 IV D2 a cada 21 dias por 3 ciclos
Ref. (2)
5-Fluorouracil + Cisplatina 5-Fluorouracil: 1.000 mg/m2/dia IV infuso contnua D1 a D5. Cisplatina: 100 mg/m2 IV D1 Semanas 1, 5, 8, e 11 Ref. (3) Irinotecano + Cisplatina Irinotecano: 65 mg/m2 IV semanalmente por 4 semanas Cisplatina: 30 mg/m2 IV semanalmente por 4 semanas a cada 6 semanas Ref. (4) Paclitaxel + Cisplatina Paclitaxel: 200 mg/m2 IV em 24 horas D1 Cisplatina: 75 mg/m2 IV D2 a cada 21 dias Paclitaxel Paclitaxel: 250 mg/m2 IV em 24 horas D1 a cada 21 dias
Ref. (5)
Ref. (6)
41
ECF Epirrubicina: 50mg/m2 IV D1 Cisplatina: 60mg/m2 IV D1 5-Fluorouracil: 225 mg/m2/dia IV D1 ao D21 a cada 21 dias Ref. (7) Oxaliplatina e Capecitabina Oxaliplatina: 30mg/m2 IV D1 Capecitabina: 1700mg/m2/dia VO D1 a D14 a cada 21 dias Ref. (8) EP Cisplatina: 30 mg/m2 IV D1 a D4 Etoposide: 120 mg/m2 IV D1 a D4 a cada 28 dias Ref. (9) Paclitaxel, Carboplatina e 5-Fluorouracl Paclitaxel: 200 mg/m2 IV D1 e D22 Carboplatina: AUC6 IV D1 e D22 2 5-Fluorouracil: 225 mg/m /dia IV contnuo D1 a D42 * Regime aplicado junto com a radioterapia no pr-operatrio. A cirurgia realizada 4 a 5 semanas aps o trmino do tratamento combinado. Ref. (10) Gencitabina, 5-Fluorouracil e Leucovorin Gencitabina: 1000 mg/m2 IV D1, D8 e D15 5-Fluorouracil: 600 mg/m2 IV D1, D8 e D15 2 Leucovorin: 25 mg/m IV D1, D8 e D15 a cada 28 dias Ref. (11)
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1. Herskovic A, et al. Combined chemotherapy eradiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med 1992;326:15931598. 2. Heath El, et al. Phase II evaluation of preoperative chemoradiation and postoperative adjuvant chemotherapy porsquamous cell and adenocarcinoma of the esophagus. J Clin Oncol 2000;18:868876. 3. Kies MS, et al. Cisplatin e5-fluorouracil in the primary management of squamous esophageal cancer. Cancer 1987;60:21562160. 4. Ilson DH, et al. Phase II trial of semanalmente irinotecan plus cisplatin in first line advanced esophageal cancer. J Clin Oncol 1999;17: 32703275. 5. Ilson DH, et al. Phase II trial of paclitaxel, fluorouracil, ecisplatin in patients with advanced carcinoma of the esophagus. J Clin Oncol 1998;16:18261834. 6. Ajani JA, et al. Paclitaxel in the treatment of carcinoma of the esophagus. Semin Oncol 1995;22 (Suppl 6):3540. 7. Cunningham D et al. Perioperative Chemotherapy versus Surgery Alone for Resectable Gastroesophageal Cancer. N Engl J Med. 2006; 355:11-20. 8. Jatoi A et al. Oxaliplatin and capecitabine in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia: a phase II study from the North Central Cancer Treatment Group. Ann Oncol. 2006. 17; 29-34. 9. Hejna M, Kornek GV et al. Effective radiochemotherapy with cisplatin and etoposide for the management of patients with locally inoperable and metastatic esophageal carcinoma. Cancer 1996 15(78): 1646-50. 10. Melucti M,et al. Preoperative therapy with concurrent paclitaxel/ carboplatin/infusional 5-FU and radiation therapy in locoregional esophageal cancer: final results of a Minnie Pearl Cancer Research Network phase II trial. Canicer J 2003;9:251-60. 11. Morgan-Meadows, et al. A phase II trial of gemcitabine, 5fluorouracil and leucovorin in advanced esophageal carcinoma. Oncology 2005;69:130-4.
43
Cncer Gstrico e Juno Gastroesofgica

Quimioterapia concomitante a radioterapia (Esquema de MacDonald) 5-Fluorouracil: 425 mg/m2 IV D1 a D5 Leucovorin: 20 mg/m2 IV D1 a D5 Radioterapia iniciando no D28 do primeiro ciclo associada a 2 ciclos de quimioterapia conforme abaixo: 5-Fluorouracil: 400 mg/m2 IV D1-4 e D23-25 da radioterapia Leucovorin: 20 mg/m2 IV D1-4 e D23-25 da radioterapia Aps trmino da radioterapia repetir mais dois ciclos de 5-Fluorouracil: 425 mg/m2 IV D1 a D5 Leucovorin: 20 mg/m2 IV D1 a D5 Ref. (1) DCF Docetaxel: 75 mg/m2 IV D1 Cisplatina: 75 mg/m2 IV em 3 horas D1 5-Fluorouracil: 750 mg/m2/dia IV infuso contnua D1 a D5 a cada 21 dias Ref. (2) CF Cisplatina: 100 mg/m2 IV em 3 horas D1 5-Fluorouracil: 1.000 mg/m2/dia IV por infuso contnua D1 a D5 a cada 28 dias Ref. (2) ECF Epirubicina: 50 mg/m2 IV D1 Cisplatina: 60 mg/m2 IV D1 5-Fluorouracil: 200 mg/m2/dia IV infuso contnua por 21 dias a cada 21 dias Ref. (4)
44
ELF Etoposide: 120 mg/m2 IV D1 a 3 Leucovorin: 300 mg/m2 IV D1 a 3 5-Fluorouracil: 500 mg/m2 IV D1 a 3 a cada 28 dias IP Irinotecano: 70 mg/m2 IV D1 e 15 Cisplatina: 80 mg/m2 IV D1 a cada 28 dias FAM 5-Fluorouracil: 600 mg/m2 IV D1, 8, 29 e 36 Adriamicina: 30 mg/m2 IV D1 e 29 Mitomicina-C: 10 mg/m2 IV D1 a cada 8 semanas
Ref. (5)
Ref. (6)
Ref. (7)
FAMTX 5-Fluorouracil: 1.500 mg/m2 IV D1, iniciando 1 hora aps o Methotrexate Leucovorin: 15 mg/m2 VO a cada 6 horas por 12 doses, iniciando 24 horas aps incio do Methotrexate Adriamicina: 30 mg/m2 IV D15 Methotrexate: 1.500 mg/m2 IV D1 a cada 28 dias Ref. (8) FAP 5-Fluorouracil: 300 mg/m2 IV D1 a 5 Adriamicina: 40 mg/m2 IV D1 Cisplatina: 60 mg/m2 IV D1 a cada 5 semanas Docetaxel + Cisplatina Docetaxel: 85 mg/m2 IV D1 Cisplatina: 75 mg/m2 IV D1 a cada 21 dias
Ref. (9)
Ref. (10)
45
5-Fluorouracil 5-Fluorouracil: 500 mg/m2 IV D1 a 5 a cada 28 dias Docetaxel Docetaxel: 100 mg/m2 IV D1 a cada 21 dias OU
Ref. (11)
Ref. (12)
Docetaxel: 35 mg/m2 IV semanalmente por 6 semanas a cada 8 semanas Ref. (12) Capecitabina Capecitabina: 2000mg/m2/dia VO D1 a D14, ciclos a cada 21 dias. Ref.(13) Cisplatina + Irinotecano Cisplatina: 30 mg/m2 IV Irinotecano: 60 mg/m2 IV Semanal x 3 semanas a cada 4 semanas
Ref. (14)
FOLFOXIRI Oxaliplatina: 85mg/m2 IV em 2 horas D1 Irinotecano: 165mg/m2 IV em 90 min D1 Leucovorin: 200mg/m2 IV em 2 horas D1 5-Fluorouracil 3200mg/m2 IV em 48 horas, infuso contnua a cada 15 dias Ref. (15) EOX Epirrubicina: 50mg/m2 IV D1 a cada 3 semanas Oxaliplatina: 130mg/m2 IV D1 a cada 3 semanas Capecitabina: 625mg/m2 VO, BID, durante todo o tratamento por 8 ciclos Ref. (16) ECX Epirrubicina: 50mg/m2 IV D1 Cisplatina: 75mg/m2 IV D1 Capecitabina: 1000mg/m2 VO, BID D1 a D14
Ref. (17)
46
EXE Oxaliplatina: 130mg/m2 IV D1 a cada 3 semanas Capecitabina: 1000mg/m2 VO, BID, continuamente Epirrubicina: 50mg/m2 IV D1 a cada 3 semanas PELF Cisplatina: 40mg/m2 IV D1 e D5 Epirrubicina: 30mg/m2 IV D1 e D5 Leucovorin: 100mg/m2 IV D1 a D4 Fluorouracil: 300mg/m2 IV D1 a D4 a cada 21 dias, total de 4 ciclos DF Docetaxel: 75mg/m2 IV D1 5-Fluorouracil: 200mg/m2 IV D1 a D21 a cada 3 semanas ECR Epirrubicina: 60 mg/m2 IV D1 Cisplatina: 60 mg/m2 IV D1 Raltitrexede: 1mg/m2 IV D1 e D8 a cada 3 semanas
Ref. (18)
Ref. (19)
Ref. (20)
Ref. (21)
Estudo ToGA Trastuzumabe: 8 mg/Kg dose inicial IV Dia 1 seguido por 6 mg/kg a cada 21 dias, at a progresso ou toxicidade intolervel, associado a: Cisplatina: 80 mg/m2 Dia 1 a cada 21 dias + 5-Fluorouracil: 800 mg/m2 Dias 1 a 5 em infuso contnua a cada 21 dias OU Capecitabina: 1g/ m2 / VO 2 x ao dia Dias 1 a 14 a cada 21 dias por 6 ciclos. Ref. (22) 1. MacDonald JS, et al. Chemoradiotherapy after surgery compared with surgery alone poradenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001; 345: 725730. 2. Ajani JA, et al. Docetaxel (D), cisplatin, 5-fluorouracil compare
47
to cisplatin (C) e5-fluorouracil (F) porchemotherapy-nave patients with metastatic or locally recurrent, unresectable gastric carcinoma (MGC): interim results of a randomized phase III trial (V3325). Proc Am Soc Clin Oncol 2003;22:249 (abstract 999). 4. Findlay M, et al. A phase II study in advanced gastro-esophageal cancer using epirubicin ecisplatin in combination with continuous infusion 5-fluorouracil (ECF). Ann Oncol 1994; 5:609616. 5. Wilke M, et al. Preliminary analysis of a randomized phase III trial of FAMTX versus ELF versus cisplatin/FU in advanced gastric cancer. A trial of the EORTC Gastrointestinal Tract Cancer Cooperative Group ethe AIO. Proc Am Soc Clin Oncol 1995;14:206a. 6. Shirao K, et al. Phase III study of irintoecan hydrochloride combined with cisplatin in patients with advanced gastric cancer. J Clin Oncol 1997;15:921927. 7. MacDonald JS, et al. 5-Fluorouracil, Adriamicina, emitomycin (FAM) combination chemotherapy poradvanced gastric cancer. Ann Intern Med 1980;93:533536. 8. Kelsen D, et al. FAMTX versus etoposide, Adriamicina, and cisplatin: a random assignment trial in gastric cancer. J Clin Oncol 1992; 10:541548. 9. Cullinan SA, et al. Controlled evaluation of three drug combination regimens versus fluorouracil alone porthe therapy of advanced gastric cancer. North Central Cancer Treatment Group. J Clin Oncol 1994;12:412416. 10. Ajani JA, et al. Multinational randomized trial of docetaxel, cisplatin with or without 5-fluorouracil in patients with advanced gastric or GE junction adenocarcinoma. Proc Am Soc Clin Oncol 2000;20: 165a (abstract 657). 11. OConnell MJ. Current status of chemotherapy poradvanced pancreatic egastric cancer. J Clin Oncol 1985;3:10321039. 12. Ajani JA. Docetaxel porgastric eesophageal carcinomas. Oncology 2002;16 (Suppl 6):8996. 13. Hong S et al: A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Ann Oncol 15:1344,2004.
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14. Pozzo C et al: Irinotecan in combination with Fluorouracil and acid folinic or with cisplatin in patients with advanced gastric cancer , Ann Oncol 2004 Dec; 15 (12) : 1773-81.15. Cao W, Yang W, Lou G, Jiang J, Geng M, Xi W, Li H, Ma T, Jin Y.Phase II trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) as first-line treatment for advanced gastric cancer. Anticancer Drugs. 2009 Apr; 20(4): 287-93. 16. Cunninghan D, Starling N et al. Capecitabine and Oxaliplatin for Advanced Esophagogastric Cancer. N Engl J Med 2008; 358:36-46. 17. Yun J, Lee J, Park SH, Park JO, Park YS, Lim HY, Kang WK. A randomised phase II study of combination chemotherapy with epirubicin, cisplatin and capecitabine (ECX) or cisplatin and capecitabine (CX) in advanced gastric cancer. Eur J Cancer. 2010 Mar; 46(5):885-91. 18. Schnnemann KR, Jensen HA, Yilmaz M et al. Phase II study of short-time oxaliplatin, capecitabine and epirubicin (EXE) as first-line therapy in patients with non-resectable gastric cancer. Br J Cancer. 2008 Sep 16;99(6):858-61. 19. Di Costanzo F, Gasperoni S, Manzione L, Bisagni G, Labianca R, Bravi S, Cortesi E et al. Adjuvant chemotherapy in completely resected gastric cancer: a randomized phase III trial conducted by GOIRC. J Natl Cancer Inst. 2008 Mar 19;100(6):388-98. Epub 2008 Mar 11. 20. Thuss-Patience PC, Kretzschmar A, Repp M, Kingreen D, Hennesser D, Micheel S, Pink D, Scholz C, Drken B, Reichardt P. Docetaxel and continuous-infusion fluorouracil versus epirubicin, cisplatin, and fluorouracil for advanced gastric adenocarcinoma: a randomized phase II study. J Clin Oncol. 2005 Jan 20;23(3):494-501. 21. Ferrari VD, Amoroso V, Valcamonico F et al. Epirubicin, cisplatin, and raltitrexed in patients with advanced gastric and hepatobiliary carcinoma: a phase II study. Am J Clin Oncol. 2004 Oct;27(5):445-8. 22. Bang, YJ, Van Cutsem, E, Feyereislova, A, et. al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled Trial. Lancet. 2010;376:687-697.
49
Tumor do Estroma Gastrointestinal (GIST)

Imatinibe Imatinibe: 400 mg/dia VO Ref. (1) Imatinibe: 400 mg VO BID Ref. (2) Sunitinibe Sunitinibe: 50mg/dia VO por 4 semanas a cada 6 semanas Ref.(3) Nilotinibe Nilotinibe: 400mg VO BID Ref. (4)
1. Demetri GD, et al. Efficacy and safety of imatinib mesylate in advancedgastrointestinal stromal tumors. N Engl J Med 2002;347: 472480. 2. Verweij J, Casali P et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial Lancet 364:1127,2004. 3. Demetri GD et al.: Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumors after failure of imatinib: a randomized controlled trial. Lancet 368:1329, 2006. 4. Montemurro M, Schffski P, Reichardt P, Gelderblom H, Schtte J, Hartmann JT, et al. Nilotinib in the treatment of advanced gastrointestinal stromal tumours resistant to both imatinib and sunitinib. Eur J Cancer. 2009 Sep; 45(13): 2293-7.
50
Hepatocarcinoma
Adriamicina Adriamicina: 2030 mg/m2 IV semanalmente Cisplatina Cisplatina: 80 mg/m2 IV D1, a cada 28 dias Capecitabina Capecitabina: 1,000 mg/m2 VO BID D114 a cada 21 dias Sorafenibe Sorafenibe: 400mg VO BID por dia Capecitabina + Cisplatina Capecitabina: 2000mg/m2/dia, BID, VO, D1 a D14 Cisplatina: 60mg/m2 IV D1 a cada 3 semanas PIAF Cisplatina: 20mg/m2 IV D1 a D4 Interferon alfa 2b 5MU/m2 SC D1 a D4 Doxorrubicina: 40mg/m2 IV D1 5-Fluorouracil: 400mg/m2 IV D1 a D4 a cada 3 semanas. Tamoxifeno Tamoxifeno: 20mg VO por dia Ref. (1)
Ref. (2)
Ref. (3)
Ref. (4)
Ref. (5)
Ref. (6)
Ref. (7)
1. Venook AP. Treatment of hepatocellular carcinoma: too many options? J Clin Oncol 1994;12:13231334.
51
2. Okada S, et al. A phase 2 study of cisplatin in patients with hepatocellular carcinoma. Oncology 1993;50:2226. 3. Aguayo A, et al. Nonsurgical treatment of hepatocellular carcinoma. Semin Oncol 2001;28:503513. 4. llovet JM. Sorafenib in advanced hepatocellular Carcinoma. N Engl J Med 2008; 359:378-390. 5. Lee JO, Lee KW, Oh DY, Kim JH, Im SA, et al.Combination chemotherapy with capecitabine and cisplatin for patients with metastatic hepatocellular carcinoma. Ann Oncol. 2009 Aug; 20(8):1402-7. 6. Yeo W, Mok TS, Zee B, Leung TW et al. A randomized phase III study of doxorubicin versus cisplatin/interferon alpha-2b/ doxorubicin/fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma. J Natl Cancer Inst. 2005 Oct 19;97(20):1532-8. 7. Barbare JC, Bouch O, Bonnetain F, Raoul JL, Rougier P, Abergel A, Boige V, Denis B, Blanchi A, Pariente A, Milan C, Bedenne L. Randomized controlled trial of tamoxifen in advanced hepatocellular carcinoma. J Clin Oncol. 2005 Jul 1; 23(19):4338-46.
52
Cncer de Vias Biliares

Gencitabina Gencitabina: 1000mg/m2 IV D1,8,15 , a cada 28 dias Ref.(1) Cisplatina + Gencitabina Cisplatina: 60mg/m2 IV D1 Gencitabina: 1250mg/m2 IV D1 e D8 a cada 21 dias GEMOX Oxaliplatina: 100mg/m2 IV D1 Gencitabina: 1000mg/m2 IV D1 a cada 14 dias GEMCAP Gencitabina: 1000mg/m2 IV D1 e D8 Capecitabina: 1300mg/m2/dia VO D1 a D14 a cada 21 dias Capecitabina + Cisplatina Capecitabina: 1250mg/m2 VO BID por 14 dias Cisplatina: 60mg/m2 IV D1 a cada 3 semanas Mitomicina + 5-Fluorouracil + Leucovorin Mitomicina C: 10mg/m2 IV D1 5-Fluorouracil: 350mg/m2 IV D1 a D4 Leucovorin: 350mg/m2 IV D1 a D4 a cada 4 semanas
Ref.(2)
Ref. (3)
Ref. (4)
Ref.(5)
Ref. (6)
53
5-Fluorouracil + Radioterapia 5-Fluorouracil: 500mg/m do D1 a D3 IV pulso na 1 e 5 semana da radioterapia OU 5-Fluorouracil: 400mg/m e Leucovorin: 20mg/m, ambos do D1 a D4 em pulso na 1 e 5 semana da radioterapia Radioterapia: concomitante ao 5-Fluorouracil na dose de 45 Gy em fraes de 180cGy + boost de 5,4-9,0Gy (dose total 54Gy). Ref. (7) Capecitabina + Radioterapia (M. D. Anderson) Capecitabina: 1500mg/m/dia VO duas vezes ao dia de segunda a sexta-feira durante todo o tratamento radioterpico. Radioterapia: concomitante a capecitabina na dose de 45 Gy com boost de 10Gy. Ref. (8) CAPOX Oxaliplatina: 130mg/m IV em 2 horas no D1 Capecitabina: 1000mg/m VO duas vezes ao dia do D1 ao D14 a cada 21 dias Ref. (9)
1. Gebbia V et al. Treatment of Inoperable and/or Metastatic Biliary Tree Carcinomas With Single-Agent Gemcitabine or in Combination With Levofolinic Acid and Infusional Fluorouracil: Results of a Multicenter Phase II Study. J Clin Oncol, 2001; 19: 4089-91. 2. Kim ST et al. A Phase II study of gemcitabine and cisplatin in advanced biliary tract cancer. Cancer , 2006: 106:1339-46
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3. Andre T, et al. Gemcitabine combined with oxaliplatin (GEMOX) in advanced biliary tract adenocarcinoma: a GERCOR study. Ann Oncol. 2004; 15: 1339-43. 4. Knoxx JJ et al. Combining Gemcitabine and Capecitabine in Patients With Advanced Biliary Cancer: A Phase II Trial. J Clin Oncol. 2005; 23:2332-8. 5. Kim TW, Chang HM, Kang HJ, Lee JR, Ryu MH, Ahn JH, Kim JH, Lee JS, Kang YK. Phase II study of capecitabine plus cisplatin as first-line chemotherapy in advanced biliary cancer. Ann Oncol. 2003 Jul;14(7):1115-20. 6. Polyzos A, Nikou G, Giannopoulos A et al. Chemotherapy of biliary tract cancer with mitomycin-C and 5-fluorouracil biologically modulated by folinic acid. A phase II study.Ann Oncol. 1996 Aug;7(6):644-5. 7. Kresl JJ, Schild SE, Henning GT, Gunderson LL, Donohue J, Pitot H, Haddock MG, Nagorney D. Adjuvant external beam radiation therapy with concurrent chemotherapy in the management of gallbladder carcinoma. Int J Radiat Oncol Biol Phys 2002: 52: 167. 8. Borghero Y, Crane, CH, Szklaruk J, Oyarzo M, et al. Extrahepatic Bile Duct Adenocarcinoma: Patients at HighRisk for Local Recurrence Treated with Surgery and Adjuvant Chemoradiation Have an Equivalent Overall Survival to Patients with Standard-Risk Treated with Surgery Alone. Annals of Surgical Oncology. 2008: 15(11):31473156. 9. Capecitabine plus oxaliplatin as First-line treatment in patients with advanced biliary sysstem adenocarcinoma: a prospective multicentre phase II trial. Br J Cancer 2008: 98: 309-315.
55
Cncer de Pncreas
5-Fluorouracil + Radioterapia 5-Fluorouracil: 500 mg/m2/dia IV D1 a 3 e D29 a 31 seguido de 5-Fluorouracil semanal iniciando no D71 Ref. (1) 5-Fluorouracil + Leucovorin 5-Fluorouracil: 425 mg/m2 IV D1 a 5 Leucovorin: 20 mg/m2 IV D1 a 5 a cada 28 dias Gencitabina + Capecitabina Gencitabina: 1.000 mg/m2 IV D1 e 8 Capecitabina: 650 mg/m2 VO BID D1 a 14 a cada 21 dias Gencitabina + Cisplatina Gencitabina: 1.000 mg/m2 IV D1, 8 e 15 Cisplatina: 50 mg/m2 IV D1 e15 a cada 28 dias GEMOX Gencitabina: 1.000 mg/m2 IV a 10 mg/m2/min D1 Oxaliplatina: 100 mg/m2 IV em 2 horas D2 a cada 2 semanas
Ref. (2)
Ref. (3)
Ref. (4)
Ref. (5)
Gencitabina + Irinotecano Gencitabina: 1.000 mg/m2 IV em 30 minutos D1 e 8 Irinotecano: 100 mg/m2 IV em 90 minutos D1 e 8 a cada 21 dias Ref. (6) FAM 5-Fluorouracil: 600 mg/m2 IV D1, 8, 29 e 36
56
Adriamicina: 30 mg/m2 IV D1 e 29 Mitomicina-C: 10 mg/m2 IV D1 a cada 56 dias
Ref. (7)
Gencitabina + Erlotinibe Gencitabina: 1.000 mg/m2 IV semanalmente por 7 semanas, seguida por uma semana de descanso e ciclos subsequentes com Gencitabina 1.000 mg/m2 IV semanalmente por 3 semanas com uma semana de descanso Erlotinibe: 100 mg VO diariamente Repetir o ciclo de 3 semanas a cada 28 dias Ref. (8) Gencitabina Gencitabina: 1,000 mg/m2 IV semanalmente por 7 semanas, seguido por uma semana de descanso Com ciclos subsequentes de 1.000mg/m2, IV semanalmente por 3 semanas com uma semana de descanso Repetir o ciclo de 3 semanas a cada 28 dias Ref. (9) OU Gencitabina: 1.000 mg/m2 IV a 10 mg/m2/min D1, 8 e15 a cada 28 dias Ref. (10) Capecitabina Capecitabina: 1.250 mg/m2 VO BID D1 a 14 a cada 21 dias FOLFOX6 Oxaliplatina: 100mg/m2 IV em 2 horas D1 Leucovorin: 400mg/m2 IV D1 5-Fluorouracil: 400mg/m2 IV pulso D1 5-Fluorouracil: 3000mg/m2 IV em 46 horas. a cada 15 dias
Ref. (11)
Ref. (12)
57
Gencitabina + Docetaxel + Capecitabina (GTX) Gencitabina: 750 mg/m IV no D4 e D11 Docetaxel: 30 mg/m IV no D4 e D11 Capecitabina: 1000-1500 mg/m VO duas vezes ao dia do D1 ao D14 a cada 2 semanas Ref. (13) FOLFIRINOX Oxaliplatina: 85mg/m IV em 2h D1 Irinotecano: 180mg/ m IV em 30 a 90 minutos D1 Leucovorin: 400mg/ m IV D1 seguido de 5-Fluorouracil 400mg/ m em pulso D1, seguido de 5Fluorouracil 2400 mg/m2 IV contnuo em 46 horas. a cada 2 semanas Ref. (14) Irinotecano Irinotecano: 350 mg/m2 Ref. (15) Docetaxel Docetaxel: 75 mg/m2 Ref. (16)
IV
D1
21 dias
IV
D1
21 dias
1. Gastrointestinal Tumor Study Group. Comparative therapeutic trial of radiation with or without chemotherapy in pancreatic carcinoma. Int J Radiat Oncol Biol Phys 1979; 5: 16431647. 2. DeCaprio JA, et al. Fluorouracil ehigh-dose leucovorin in previously untreated patients with advanced adenocarcinoma of the pancreas: results of a phase II trial. J Clin Oncol 1991; 9: 21282133. 3. Hess V, et al. Combining capecitabine and gemcitabine in patients with advanced pancreatic carcinoma: a phase I/II trial. J Clin Oncol 2003;21:6668.
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4. Philip PA, et al. Phase II study of gemcitabine ecisplatin in the treatment of patients with advanced pancreatic carcinoma. J Clin Oncol 2001; 92:569577. 5. Louvet C, et al. Gemcitabine combined with oxaliplatin in advanced pancreatic adenocarcinoma: final results of a GERCOR multicenter phase II study. J Clin Oncol 2002; 20: 15121518. 6. Rocha-Lima C, et al. Irinotecan plus gemcitabine induces both radiographic and CA19-9 tumor marker responses in patients with previously untreated advanced pancreatic cancer. J Clin Oncol 2002;20:11821191. 7. Leonard RC, et al. Chemotherapy prolongs survival in inoperable pancreatic carcinoma. Br J Cancer 1994; 81: 882885. 8. Moore MJ, et al. Erlotinib plus gemcitabine compared to gemcitabine alone in patients with advanced pancreatic cancer. A phase III trial of the NCIC-CTG. J Clin Oncol 2005; 23:16S (abstract 1). 9. Burris HA, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy porpatients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997;15:24032413. 10. BreR, et al. A phase I trial of semanalmente gemcitabine administered as a prolonged infusion in patients with pancreatic cancer eother solid tumors. Invest New Drugs 1997;15:331341. 11. Cartwright TH, et al. Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. J Clin Oncol 2002; 20:160164. 12. Ghosn M, Farhat F, Kattan J, Younes F, Moukadem W, Nasr F, Chahine G. FOLFOX-6 combination as the first-line treatment of locally advanced and/or metastatic pancreatic cancer. Am J Clin Oncol. 2007 Feb;30(1):15-20. 13. Fine RL, et al. The GTX regimen: a biochemically synergistic combination for advanced pancreatic cancer (PC). Proc Am Soc Clin Oncol 2003;22:281 (abstract 1129).
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14. T. Conroy, F. Desseigne, et al. Randomized phase III trial comparing FOLFIRINOX (F: 5FU/leucovorin [LV], irinotecan [I], and oxaliplatin [O]) versus gemcitabine (G) as first-line treatment for metastatic pancreatic adenocarcinoma (MPA): Preplanned interim analysis results of the PRODIGE 4/ACCORD 11 trial. J Clin Oncol 28:15s, 2010 (suppl; abstr 4010). 15. Wagener DJ, et al. Phase II trial of CPT-11 in patients with advanced pancreatic cancer, an EORTC early clinical trials group study. Ann Oncol 1995:6:129-32. 16. Lenzi RL, et al. Phase II study of docetaxel in patients with pancreatic cancer previously untreated with cytotoxic chemotherapy. Cancer Invest 2002; 20: 464-72. Cncer Invest 2002;20:464-72.
60
Cncer de Cabea e Pescoo

Cisplatina concomitante a radioterapia Cisplatina: 100mg/m2 IV em 2 horas nos D1,22, 43 Ref. (1) Cetuximabe concomitante a radioterapia Cetuximabe: 400mg/m2 (dose de ataque na primeira semana) seguido por 250mg/m2 por semana durante a radioterapia Ref. (2) TPF Docetaxel: 75 mg/m2 IV em 1 hora D1 Cisplatina: 75mg/m2 IV em 1 hora D1 5-Fluorouracil: 750 mg/m2 em 24 horas D1 a 5 a cada 21 dias
Ref. (3)
TIP Paclitaxel: 175 mg/m2 IV em 3 horas D1 Ifosfamida: 1.000 mg/m2 IV em 2 horas D1 a 3 Mesna: 400 mg/m2 IV antes da Ifosfamida e 200 mg/m2 IV, 4 horas aps Ifosfamida Cisplatina: 60 mg/m2 IV D1 a cada 2128 dias Ref. (4) TIC Paclitaxel: 175 mg/m2 IV em 3 horas D1 Ifosfamida: 1.000 mg/m2 IV em 2 horas D13 Mesna: 400 mg/m2 IV antes da Ifosfamida e 200 mg/m2 IV, 4 horas aps Ifosfamida Carboplatina: AUC 6 IV D1 a cada 2128 dias Ref. (5)
61
Paclitaxel + Carboplatina Paclitaxel: 175 mg/m2 IV em 3 horas D1 Carboplatina: AUC 6 IV no dia 1 a cada 21 dias Paclitaxel + Cisplatina Paclitaxel: 175 mg/m2 IV em 3 horas D1 Cisplatina: 75 mg/m2 IV D2 G-CSF: 5 g/kg/dia SC D410 a cada 21 dias
Ref. (6)
Ref. (7)
PF Cisplatina: 100 mg/m2 IV D1 5-Fluorouracil: 1.000 mg/m2/dia IV infuso contnua D1 a D5 a cada 2128 dias Ref. (8) PFL Cisplatina: 100 mg/m2 IV D1 5-Fluorouracil: 800 mg/m2/dia IV infuso contnua D1 a D5 Leucovorin: 50 mg/m2 VO a cada 6 horas D15 a cada 21 dias Ref. (9) Carboplatina + 5-Fluorouracil Carboplatina: 300400 mg/m2 IV D1 5-Fluorouracil: 600 mg/m2 IV D1 a cada 21 dias VP Vinorelbina: 25 mg/m2 IV D1 e 8 Cisplatina: 80 mg/m2 IV D1 a cada 21 dias Docetaxel Docetaxel: 100 mg/m2 IV em 1 hora D1 a cada 21 dias
Ref. (13)
Ref. (14)
Ref. (15)
62
Paclitaxel Paclitaxel: 250 mg/m2 IV em 24 horas D1 a cada 21 dias Ref. (16) OU Paclitaxel: 137175 mg/m2 IV em 3 horas D1 a cada 21 dias Ref. (16) Methotrexate Methotrexate: 40 mg/m2 IV or IM semanalmente Vinorelbina Vinorelbina: 30 mg/m2 IV semanalmente
Ref. (17)
Ref. (18)
PF + Cetuximabe Cisplatina: 100mg/m2 IV em 1 hora D1 Fluorouracil: 1000mg/m2 IV em 24horas D1 a D4 Cetuximabe: 400mg/m2 (dose de ataque) seguido por 250mg/m2 IV por semana. A cada 21 dias, por 6 ciclos. Ref. (19) Gencitabina Gencitabina: 1250mg/m2, IV , D1 e D8, a cada 21 dias. Ref. (20) Capecitabina Capecitabina: 1250mg/m2 VO BID D1 a D14 a cada 21 dias Ifosfamida Ifosfamida: 3g/m2 IV D1 a D3 Mesna: 1800mg/m2 IV D1 a D3 a cada 3 semanas
Ref. (21)
Ref. (22)
Cisplatina + 5-Fluorouracil + Radioterapia Cisplatina: 100 mg/m2 IV D1 5-Fluorouracil: 1000 mg/m2 D1 a 5 em infuso contnua Radioterapia concomitante. a cada 21 a 28 dias no total de 3 ciclos Ref. (32)
63
Cisplatina + Radioterapia Cisplatina: 100 mg/m2 D1, 22 e 43 Radioterapia concomitante
Ref. (33)
Cisplatina + 5-Fluorouracil + Docetaxel Cisplatina: 75 mg/m2 IV D1 5-Fluorouracil: 750mg/m2/dia IV D1 a D5 Infuso contnua Docetaxel: 75mq/m2 IV D1 a cada 21 dias por 3 ciclos O regime acima administrado antes da cirugia e seguido por quimio-radioterapia, com o regime abaixo: Cisplatina: 100 mg/m2 IV D1 a cada 21 dias por 3 ciclos Ref. (34) Cisplatina + 5-Fluorouracil + Paclitaxel Cisplatina: 100 mg/m2 IV D2 2 5-Fluorouracil: 500 mg/m /dia IV D2 a D6 Infuso contnua Paclitaxel: 175 mg/m2 IV D1 a cada 21 dias por 3 ciclos O regime acima administrado antes da cirugia e seguido por quimio-radioterapia, com o regime abaixo: Cisplatina: 100 mg/m2 IV D1 a cada 21 dias por 3 ciclos Ref. (35) Paclixatel + Doxorrubicina peguilada Paclitaxel: 175 mg/m2 IV D1 21 dias 2 Doxorrubicina: 40 mg/m IV lipossomal peguilada D1 28 dias Ref. (40) Paclitaxel + Gencitabina Paclitaxel: 175 mg/m2 IV 2 Gencitabina: 1000 mg/m IV Ref. (41)
D1 D1 e D8 a cada 21 dias
64
Linfoepitelioma Nasofaringe
Quimioterapia + Radioterapia Cisplatina: 100 mg/m2 IV D1, 22 e 43 durante radioterapia Aps o trmino da quimio e radioterapia a quimioterapia segue com o seguinte protocolo: Cisplatina: 80 mg/m2 IV D1 5-Fluorouracil: 1,000 mg/m2/dia IV infuso contnua D1-4 a cada 28 dias por um total de 3 ciclos Ref. (12) PBF Cisplatina: 100mg/m2 IV D1 Bleomicina: 15 mg IV D1 Bleomicina: 16mg/m2/dia em infuso contnua D1 a D5 Fluorouracil 650mg/m2/dia IV D1 a D5 a cada 28 dias Ref. (23) Paclitaxel concomitante a radioterapia Paclitaxel: 35mg/m2 IV semanal por 6 semanas Aps trmino da radioterapia: Paclitaxel: 135mg/m2 IV D1 Cisplatina: 30mg/m2 IV D1 a D3 a cada 4 semanas por 2 ciclos
Ref. (24)
Cisplatina + Epirrubicina Cisplatina: 100mg/m2 IV D1 Epirrubicina: 90mg/m2 IV D1 a cada 21 dias Repetir por 3 ciclos seguidos por radioterapia concomitante a Cisplatina: 100mg/m2 IV a cada 21 dias Ref. (25)
65
Capecitabina + Cisplatina Capecitabina: 1000mg/m2 VO BID D1 a D14 Cisplatina: 80 mg/m2 IV D1 a cada 3 semanas Ref. (26) Gencitabina Gencitabina: 1000mg/m2 IV D1,8,15 a cada 4 semanas Ref. (27) Docetaxel + Cisplatina Docetaxel: 60mg/m2 IV D1 Cisplatina: 60mg/m2 IV D1 a cada 3 semanas Ref. (28) Gencitabina + Cisplatina Gencitabina: 1000mg/m2 IV D1,8,15 Cisplatina: 50mg/m2 IV D1 e D8 a cada 28 dias Ref. (29) Ifosfamida + 5-Fluorouracil + Leucovorin Ifosfamida: 1.200 mg/m2 (associado a Mesna) IV D1 a D5 5-Fluorouracil: 375mg/m2 IV D1 a D5 Leucovorin: 20mg/m2 IV D1 a D5 a cada 21 dias Ref. (30) BEC Bleomicina: 15mg IV D1 seguido por 12mg/m2/dia em infuso contnua D1 a D5 Epirrubicina: 70mg/m2 IV D1 Cisplatina: 100mg/m2 IV D1 a cada 3 semanas Ref. (31)
66
Carboplatina + 5-Fluorouracil Carboplatina: 300 mg/m2 IV D1 5-Fluorouracil: 1000 mg/m2 IV D1 a D3 Infuso contnua a cada 21 dias por 3 ciclos Ref. (36) Carboplatina + Paclitaxel Carboplatina: AUC 6 IV pulso D1 2 Paclitaxel: 135 mg/m IV D1 a cada 21 dias por 6 ciclos Ref. (37) Cisplatina + Epirrubicina + Bleomicina (BEC) Cisplatina: 100 mg/m2 IV D1 Epirrubicina: 80 mg/m2 IV D1 Bleomicina: 15 mg IV pulso D1 2 Bleomicina: 16 mg/m IV D1 a D5 Infuso contnua a cada 28 dias por 3 ciclos Ref. (38) Docetaxel semanal Docetaxel: 40 mg/m2 Ref. (39)
IV
D1
Semanal
1. Forastiere AA. et al. Concurrent Chemotherapy and Radiotherapy for Organ Preservation in Advanced Laryngeal Cancer. N Engl J Med 349:2091, 2003. 2. Bonner JA. et al Radiotherapy plus Cetuximab for SquamousCell Carcinoma of the Head and Neck. N Engl J Med 2006; 354:567-578. 3. Vermorken JB et al. Cisplatin, Fluorouracil, and Docetaxel in Unresectable Head and Neck Cancer. N Engl J Med 357: 1695,2007. 4. Shin DS, et al. Phase II trial of paclitaxel, ifosfamide, and cisplatin in patients with recurrent head eneck squamous cell carcinoma. J Clin Oncol 1998;16:1325-1330.
67
5. Shin DM, et al. Phase II study of paclitaxel, ifosfamide, and carboplatin in patients with recurrent or metastatic head eneck squamous cell carcinoma of the head eneck (SCCHN). Cancer 1999; 91:1316-1323. 6. Fountzilas G, et al. Paclitaxel and carboplatin in recurrent or metastatic head and neck cancer: a phase II study. Semin Oncol 1997; 24 (Suppl 2):65-67. 7. Hitt R, et al. A phase I/II study of paclitaxel plus cisplatin as firstline therapy fo rhead and neck cancer. Semin Oncol 1995;22 (Suppl 15):50-54. 8. Kish JA, et al. Cisplatin and 5-fluorouracil infusion in patients with recurrent and disseminated epidermoid cancer of the head and neck. Cancer 1984;53:1819-1824. 9. Vokes EE, et al. Cisplatin, 5-fluorouracil, and high-dose oral leucovorin for advanced head and neck cancer. Cancer 1989;63 (Suppl 6):10481053. 10. Veterans Affairs Laryngeal Cancer Study Group. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med 1991;324: 1685-1690. 11. Forastiere AA, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 2003;349:2091-2098. 12. Al-Sarraf M, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized intergroup study 0099. J Clin Oncol 1998;16:1310-1317. 13. Forastiere AA, et al. Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head eneck: a Southwest Oncology Group study. J Clin Oncol 1992;10:12451251. 14. Gebbia V, et al. Vinorelbine plus cisplatin in recurrent or previously untreated unresectable squamous cell carcinoma of the head and neck. Am J Clin Oncol 1995;18:293296.
68
15. Dreyfuss A, et al. Taxotere for advanced, inoperable squamous cell carcinoma of the head and neck (SCCHN). Proc Am Soc Clin Oncol 1995;14:875a. 16. Forastiere AA. Current and future trials of Taxol (paclitaxel) in head and neck cancer. Ann Oncol 1994;5 (Suppl 6):5154. 17. Hong WK, et al. Chemotherapy in head and neck cancer. N Engl J Med 1983;308:75-79. 18. Degardin M, et al. An EORTC-ECSG phase II study of vinorelbine in patients with recurrent and/or metastatic squamous cell carcinomaof the head and neck. Ann Oncol 1998; 9:1103-1107. 19. Vermorken JB, et al. Platinum Based Chemotherapy plus cetuximab in Head and neck cancer. N Engl J Med 2008; 359.1116. 20. van Herpen CM, et al. Phase II study on gemcitabine in recurrent and/or metastatic adenoid cystic carcinoma of the head and neck (EORTC 24982). Eur J Cancer. 2008 Nov; 44(17):2542-5. 21. Martinez-Trufero J, Isla D, Adansa JC et al. Phase II study of capecitabine as palliative treatment for patients with recurrent and metastatic squamous head and neck cancer after previous platinum-based treatment. Br J Cancer. 2010 Jun 8;102(12):1687-91. 22. Martn M, Diaz-Rubio E et al. Ifosfamide in advanced epidermoid head and neck cancer. Cancer Chemother Pharmacol. 1993;31(4):340-2. 23. Boussen H, Cvitkovic E, Wendling JL et al. Chemotherapy of metastatic and/or recurrent undifferentiated nasopharyngeal carcinoma with cisplatin, bleomycin, and fluorouracil. J Clin Oncol. 1991 Sep;9(9):1675-81 24. Hu W, Ding W, Yang H, Shao M. et al. Weekly paclitaxel with concurrent radiotherapy followed by adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma. Radiother Oncol. 2009 Dec; 93(3):488-91. 25. Airoldi M, Gabriele AM, Garzaro M et al. Induction chemotherapy with cisplatin and epirubicin followed by radiotherapy and concurrent cisplatin in locally advanced
69
nasopharyngeal carcinoma observed in a non-endemic population.Radiother Oncol. 2009 Jul;92(1):105-10. 26. Li YH, Wang FH, Jiang WQ et al. Phase II study of capecitabine and cisplatin combination as first-line chemotherapy in Chinese patients with metastatic nasopharyngeal carcinoma. Cancer Chemother Pharmacol. 2008 Aug; 62(3): 539-44. 27. Zhang L, Zhang Y et al. Phase II clinical study of gemcitabine in the treatment of patients with advanced nasopharyngeal carcinoma after the failure of platinum-based chemotherapy. Cancer Chemother Pharmacol. 2008 Jan;61(1):33-8 28. Chua DT, Sham JS, Au GK.A phase II study of docetaxel and cisplatin as first-line chemotherapy in patients with metastatic nasopharyngeal carcinoma. Oral Oncol. 2005 Jul;41(6):589-95. 29. Ngan RK, Yiu HH, Lau WH et al. Combination gemcitabine and cisplatin chemotherapy for metastatic or recurrent nasopharyngeal carcinoma: report of a phase II study. Ann Oncol. 2002 Aug;13(8):1252-8. 30. Chua DT, Kwong DL, Sham JS, Au GK, Choy D.A phase II study of ifosfamide, 5-fluorouracil and leucovorin in patients with recurrent nasopharyngeal carcinoma previously treated with platinum chemotherapy. 2000 Apr;36(6):736-41. 31. No authors listed. Preliminary results of a randomized trial comparing neoadjuvant chemotherapy (cisplatin, epirubicin, bleomycin) plus radiotherapy vs. radiotherapy alone in stage IV(> or = N2, M0) undifferentiated nasopharyngeal carcinoma: a positive effect on progression-free survival. International Nasopharynx Cancer Study Group. VUMCA I trial. Int J Radiat Oncol Biol Phys. 1996 Jun 1;35(3):463-9. 32. Veterans Affairs Laryngeal Cancer Study Group. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med 1991;324:1685-90. 33. Forastiere AA et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 2003;349:2091-2098.
70
34. Hitt R, et al. Randomized phase I/II clinical trial of induction chemotherapy with either cisplatin / 5-fluorouracil (PF) or docetaxel /cisplatin / 5-fluorouracil (TPF) followed by chemoradiotherapy (CRT) vs. CRT alone form in patients with unresectable locally advanced head and neck cancer (abst 5515). J Clin Oncol. 2006;24 Suppl 18: 283s. 35. Hitt R, et al. Phase III Study Comparing Cisplatin Plus Fluorouracil to Paclitaxel, Cisplatin, and Fluorouracil Induction Chemotherapy Followed by Chemoradiotherapy in Locally Advanced Head and Neck Cancer. J Clin Oncol 2005;23:8636-45. 36. Yeo W. et al. Phase II study of the combination of carboplatin and 5-fluorouracil in metastatic nasopharyngeal carcinoma. Cancer Chemother Pharmacol 1996;38:466-70. 37. Yeo W.et al. A phase II study of combination paclitaxel and carboplatin in advanced nasopharyngeal carcinoma. Eur J Cancer 1998;34:2027-31. 38. Fandi A, et al. Long-Term Disease-Free Survivors in Metastatic Undifferentiated Carcinoma of Nasopharyngeal Type. J Clin Oncol 2000;18:1324-30. 39. Guardiola E, et al. Results of a randomized phase II study comparing docetaxel with methotrexate in patients with recurrent head and neck cancer. Eur J Cancer 2004;40:2071-6. 40. Fountzilas G, et al. Paclitaxel and gemcitabine vs. paclitaxel and pegylated liposomal doxorubicin in advanced nonnasopharyngeal head and neck cancer. An efficacy and cost analysis randomized study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol 2006;17:1560-7. 41. Fountzilas G, et al. Paclitaxel and gemcitabine vs. paclitaxel and pegylated liposomal doxorubicin in advanced nonnasopharyngeal head and neck cancer. An efficacy and cost analysis randomized study conducted by the Hellenic Cooperative Oncology Group Ann Oncol 2006;17:1560-7.
71
Cncer de Tireide
Adriamicina + Cisplatina Adriamicina: 60 mg/m2 IV D1 Cisplatina: 40 mg/m2 IV D1 a cada 21 dias Ref. (1) Sorafenibe Sorafenibe: 400mg VO BID Ref. (2) Paclitaxel Paclitaxel: 120 mg/m2 IV durante 96 horas a cada 21 dias Ref. (3)
1. Shimaoka K, et al. A randomized trial of Adriamicina versus Adriamicina plus cisplatin in patients with advanced thyroid carcinoma. Cancer 1985;56:21552160. 2. Lam ET, Ringel MD, Kloos RT, Prior TW et al. Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer. J Clin Oncol. 2010 May 10;28(14):2323-30. 3. Ain KB, Egorin MJ, DeSimone PA. Treatment of anaplastic thyroid carcinoma with paclitaxel: phase 2 trial using ninety-six-hour infusion. Thyroid. 2000;10:587-94.
72
Cncer de Glndula Salivar

Adriamicina + Cisplatina Adriamicina: 50mg/m2 IV D1 Cisplatina: 20mg/m2/dia IV D1 a D5 a cada 3 semanas Paclitaxel + Carboplatina Paclitaxel: 175mg/m2 IV D1 Carboplatina: AUC 5 IV D1 a cada 21 dias Ciclofosfamida Ciclofosfamida: 1000mg/m2 IV D1 a cada 21 dias CAP Ciclofosfamida: 500mg/m2 IV D1 Doxorrubicina: 50mg/m2 IV D1 Cisplatina: 50mg/m2 IV D1 a cada 28 dias PAF Cisplatina: 50mg/m2 IV D1 e D8 Doxorrubicina: 30mg/m2 IV D1 e D8 5-Fluorouracil: 500mg/m2 IV D1 e D8 a cada 28 dias Epirrubicina Epirrubicina: 90mg/m2 IV D1 a cada 21 dias
Ref. (1)
Ref. (2)
Ref.(3)
Ref. (4)
Ref. (5)
Ref. (6)
73
Cisplatina + Vinorelbina Cisplatina: 80mg/m2 IV D1 Vinorelbina: 25mg/m2 IV D1 e D8 a cada 3 semanas
Ref. (7)
1. de Haan LD, De Mulder PH, Vermorken JB, Schornagel JH, Vermey A, Verweij J. Cisplatin-based chemotherapy in advanced adenoid cystic carcinoma of the head and neck. Head Neck. 1992 Jul-Aug;14(4):273-7. 2. Airoldi M, Fornari G, Pedani F, Marchionatti S, Gabriele P, Succo G, Bumma C. Paclitaxel and carboplatin for recurrent salivary gland malignancies. Anticancer Res. 2000 SepOct;20(5C):3781-3. 3. Spiers A, Esseltine DLW, et al. Metastatic Adenoid Cystic Carcinoma of Salivary Glands: Case Reports and Review of the Literature. Cancer Control Journal. Vol 3, No. 4 July/August 1996. 4. Dreyfuss AI, Clark JR et al. Cyclophosphamide, doxorubicin, and cisplatin combination chemotherapy for advanced carcinomas of salivary gland origin. Cancer. 60:2869-2872, 1987. 5. Venook AP, Tseng A, et al. Cisplatin, Doxorubicin, and 5Fluorouracil Chemotherapy for Salivary Gland Malignancies: A Pilot Study of the Northern California Oncology Group. JCO June 1, 1987 vol. 5 no. 6 951-955 6. Vermorken JB, Verweij J et al. Epirubicin in patients with advanced or recurrent adenoid cystic carcinoma of the head and neck: A phase II study of the EORTC Head and Neck Cancer Cooperative Group . Annals of Oncology Volume4, Issue 9 Pp. 785-788. 7. Airoldi M,Pedani F, Succo G et al. Phase II Randomized Trial Comparing Vinorelbine versus Vinorelbine plus cisplatin in patients with recurrent salivary gland malignancies. Cancer 2001; 91: 541-7.
74
Cncer de Bexiga
Cisplatina + Gencitabina Cisplatina: 75mg/m2 IV 2 Gencitabina: 1000mg/m IV a cada 28 dias Carboplatina + Gencitabina Carboplatina: AUC 4 Gencitabina: 1000mg/m2 a cada 21 dias D1 D1, D8, D15 Ref. (1)
IV IV
D1 D1, D8 Ref. (2)
Gemcitabina + Paclitaxel Gencitabina: 1000mg/m2 Paclitaxel: 200mg/m2 a cada 21 dias
IV IV
D1, D8, D15 D1 Ref. (3)
MVAC Methotrexate: 30mg/m2 Vinblastina: 3mg/m2 Doxorrubicina: 30mg/m2 Cisplatina: 70mg/m2 a cada 28 dias
IV IV IV IV
D1, D15, D22 D2, D15, D22 D2 D2 Ref. (4)
CISCA Ciclofosfamida: 650mg/m2 Adriamicina: 50mg/m2 Cisplatina: 100mg/m2 a cada 21 dias
IV IV IV
D1 D1 D2 Ref. (5)
75
CMV Cisplatina: 100mg/m2 Methotrexate: 30mg/m2 Vinblastina: 4mg/m2 Ref. (6) Docetaxel + Cisplatina Docetaxel: 75mg/m2 Cisplatina: 75mg/m2 Paclitaxel + Carboplatina Paclitaxel: 225mg/m2 Carboplatina: AUC 6 Ref. (7) CAP Ciclofosfamida: 400mg/m2 Doxorrubicina: 40mg/m2 Cisplatina: 75mg/m2 Ref. (8) Gencitabina Gencitabina: 1200mg/m2 a cada 28 dias Ref. (9) Paclitaxel Paclitaxel: 250mg/m2 24 horas a cada 21 dias OU Paclitaxel: 80mg/m2 a cada 28 dias Ref. (11)
IV D2 IV D1, D8 IV D1, D8
a cada 21 dias
IV IV
D1 D1 a cada 21 dias
IV IV
IV IV IV
D1 D1 D1 a cada 21 dias
IV
D1, D8, D15
IV
D1 em infuso de Ref. (10)
IV
D1, D8, D15
76
Carboplatina + Paclitaxel + Gencitabina Paclitaxel: 80mg/m IV D1 e D8 Carboplatina: AUC 5 IV D1 Gencitabina: 800mg/m IV D1 e D8 a cada 21 dias Ref. (12) Cisplatina + Radioterapia Cisplatina: 100mg/m IV em 2 aplicaes, na 1 e 4 semana da Radioterapia. Radioterapia: dose total de 40 Gy em fraes de 180 cGy . Ref. (13) Gencitabina + Paclitaxel + Cisplatina Gencitabina: 1000mg/m IV D1 e D8 Paclitaxel: 80mg/m IV D1 e D8 Cisplatina: 70 mg/m IV D1 a cada 21 dias Ref. (14) Pemetrexede Pemetrexede: 500 mg/m IV D1 a cada 21 dias Ref. (15) Vinflunina Vinflunina: para pacientes com ECOG PS (0) a dose recomendada de 320mg/m durante 20 minutos no D1. Para pacientes com ECOG PS (1) ou irradiao plvica prvia iniciar com a dose de 280mg/m e escalonar at a dose ideal de 320mg/m. Ref. (16)
77
1. Kaufman, D., et al. Phase II trial of gemcitabine plus cisplatin in patients with metastatic urothelial cancer. J Clin Oncol, 2000. 18(9): p. 1921-7. 2. Linardou, H., et al. Gemcitabine and carboplatin combination as first-line treatment in elderly patients and those unfit for cisplatin-based chemotherapy with advanced bladder carcinoma: Phase II study of the Hellenic Co-operative Oncology Group. Urology, 2004. 64(3): p. 479-84. 3. Meluch, A.A., et al. Paclitaxel and gemcitabine chemotherapy for advanced transitional-cell carcinoma of the urothelial tract: a phase II trial of the Minnie pearl cancer research network. J Clin Oncol, 2001. 19(12): p. 3018-24. 4. Sternberg, C.N., et al. Methotrexate, vinblastine, doxorubicin, and cisplatin for advanced transitional cell carcinoma of the urothelium. Efficacy and patterns of response and relapse. Cancer, 1989. 64(12): p. 2448-58. 5. Logothetis CJ, Dexeus FH, Chong C, et, al. Cisplatin, cyclophosphamide and doxorubicin chemotherapy for unresectable urothelial tumors: The M.D. Anderson Experience. J Urol. 1989; 141:33-37. 6. Harker, W.G., et al. Cisplatin, methotrexate, and vinblastine (CMV): an effective chemotherapy regimen for metastatic transitional cell carcinoma of the urinary tract. A Northern California Oncology Group study. J Clin Oncol, 1985. 3(11): p. 1463-70. 7. Vaughn, D.J., et al. Phase II study of paclitaxel plus carboplatin in patients with advanced carcinoma of the urothelium and renal dysfunction (E2896): a trial of the Eastern Cooperative Oncology Group. Cancer, 2002. 95(5): p. 1022-7. 8. Okajima E, Ozono S, Hirao Y, et. al. Neoadjuvant therapy for locally invasive bladder cancer. Urol Int. 1989;44 (6):332-337. 9. Moore, M.J., et al. Gemcitabine: a promising new agent in the treatment of advanced urothelial cancer. J Clin Oncol, 1997. 15(12): p. 3441-5.
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10. Roth, B.J., et al. Significant activity of paclitaxel in advanced transitional-cell carcinoma of the urothelium: a phase II trial of the Eastern Cooperative Oncology Group. J Clin Oncol, 1994. 12(11): p. 2264-70. 11. Vaughn, D.J., et al. Phase II trial of weekly paclitaxel in patients with previously treated advanced urothelial cancer. J Clin Oncol, 2002. 20(4): p. 937-40. 12. White RWV,,Lara P, Goldman B, Tangen C, Smith DC, et al. A Sequential Treatment Approach to Myoinvasive Urothelial Cancer: A Phase II Southwest Oncology Group Trial (S0219). The Journal of Urology: 2009; 181;2480-2481 13. Shipley WU, Winter KA, Kaufman DS, Lee WR, Heney NM, Tester WR, Donnelly BJ, Venner PM, Perez CA, Murray KJ, Doggett RS, True LD. Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03. J Clin Oncol. 1999;17(4):1327-8. 14. Bellmunt J, Von der Maase J, Mead GM, Heyer J, Houede N, et al. Randomized phase III study comparing paclitaxel/ cisplatin/ gemcitabine (PCG) and gemcitabine/cisplatin (GC) in patients with locally advanced (LA) or metastatic (M) urothelial cancer without prior systemic therapy; EORTC30987/Intergroup Study. Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: LBA5030. 15. Sweeney CJ, et al. Phase II Study of Pemetrexed for SecondLine Treatment of Transitional Cell Cancer of the Urothelium. J Clin Oncol 2006;24:3451-57 16. Bellmunt J, Theodore C, DemKov T, Komyakov B, Sengelov L, Daugaard G, Caty A, et al. Phase III Trial of Vinflunine Plus Best Suportive Care Compared with Best Supportive Care Alone After Platinum Containing Regimen in Patients With Advanced Transitional Cell Carcinoma of the Urothelial Tract (TCCU). J Clin Oncol 2009: 27: 4454-4461.
79
Cncer Renal
Bevacizumabe+ Interferon Alfa Bevacizumabe: 10mg/kg IV Interferon-alfa: 9 milhes UI SC Por 1 ano D1, D14 3X/semana Ref. (1)
Interferon Alfa + Interleucina 2 Interferon alfa: 9 milhes U SC D1 a D4 Interleucina 2: 12 milhes U SC D1 a D4 em 4 semanas a cada 6 semanas Ref. (2) Sunitinibe Sunitinibe: 50mg a cada 6 semanas Sorafenibe Sorafenibe: 400mg sem interrupo Tensirolimo Tensirolimo: 25mg Ref. (5)
VO
D1 a D28 Ref. (3)
VO (2X/dia)
Contnuo Ref. (4)
IV
D1
Semanal
Interferon Alfa Interferon alfa: 5-15milhes/UI Ref. (6) Interleucina 2 Interleucina 2: 720000UI/KG 8-12 semanas
SC
3-5X/semana
IV
12/12H D1-5, 15-19 Ref. (7)
80
Everolimo Everolimo: 10mg Ref. (8) Pazopanibe Pazopanibe: 800mg Ref. (9)
VO
dia
Contnuo
VO
dia
Contnuo
1. Rini, B.I., Bevacizumab plus interferon-alpha versus interferon-alpha monotherapy in patients with metastatic renal cell carcinoma: Results of overall survival for CALGB 90206 journal of clinical oncology, 2009. 27(18S): p. abstract 5020. 2. Atzpodien, J., et al. European studies of interleukin-2 in metastatic renal cell carcinoma. Semin Oncol, 1993. 20(6 Suppl 9): p. 22-6. 3. Motzer, R.J. and R.M. Bukowski, Targeted therapy for metastatic renal cell carcinoma. J Clin Oncol, 2006. 24(35): p. 5601-8. 4. Ratain, M.J., et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol, 2006. 24(16): p. 2505-12. 5. Hudes, G., et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med, 2007. 356(22): p. 2271-81. 6. Minasian, L.M., et al. Interferon alfa-2a in advanced renal cell carcinoma: treatment results and survival in 159 patients with long-term follow-up. J Clin Oncol, 1993. 11(7): p. 1368-75. 7. Acquavella, N., et al. Toxicity and activity of a twice daily high-dose bolus interleukin 2 regimen in patients with metastatic melanoma and metastatic renal cell cancer. J Immunother, 2008. 31(6): p. 569-76.
81
8. Motzer, R.J., et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebocontrolled phase III trial. Lancet, 2008. 372(9637): p. 449-56. 9. Sternberg CN, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 2010;28(6):1061-1068.
82
Cncer de Prstata
Flutamida + Leuprorrelina Flutamida: 250mg VO TID Leuprorrelina: 7,5mg IM a cada 28 dias ou 22,5 mg IM a cada 12 semanas Ref. (01) Flutamida + Gosserrelina Flutamida: 250 mg VO TID Gosserrelina: 10,8 mg SC a cada 12 semanas Docetaxel + Prednisona Docetaxel: 75 mg/m IV D1 Prednisona: 5 mg VO BID a cada 21 dias no total de 10 ciclos
Ref. (02)
Ref. (03)
Docetaxel + Estramustina Docetaxel: 35 mg/m IV D2 das semanas 1 e 2 Estramustina: 420 mg VO nas primeiras 4 doses e 280 mg VO nas prximas 5 doses D1 ao D3 das semanas 1 e 2 a cada 21 dias Ref. (04) Mitoxantrona + Prednisona Mitoxantrona: 12 mg/m IV D1 Prednisona: 5 mg VO BID a cada 21 dias
Ref. (05)
Docetaxel Docetaxel: 20-40 mg/m semanalmente por 3 semanas a cada 4 semanas Ref. (06) Gosserrelina Gosserrelina: 3,6 mg SC D1 a cada 28 dias
83
OU Gosserrelina: 10,8 mg SC D1 a cada 12 semanas Leuprorrelina Leuprorrelina: 7,5 mg IM D1 a cada 28 dias OU Leuprorrelina: 22,5 mg IM D1 a cada 12 semanas Bicalutamida Bicalutamida: 50 mg VO diariamente Flutamida Flutamida: 250 mg VO TID
Ref. (07)
Ref. (08)
Ref. (09)
Ref. (10)
Nilutamida Nilutamida: 300 mg VO do D1 ao D30, e ento 150 mg VO diariamente Ref. (11) Prednisona Prednisona: 5 mg VO BID Cetoconazol Cetoconazol: 1200 mg VO diariamente Paclitaxel Paclitaxel: 135-170 mg/m2 IV em 24 horas D1 a cada 21 dias OU
Ref. (12)
Ref. (13)
Ref. (14)
84
Paclitaxel: 150 mg/m2 IV D1 em infuso de 1 hora a cada 6 semanas. a cada 8 semanas Ref. (15) DES Dietilestilbestrol: 1 a 3 mg VO no dia Cabazitaxel + Prednisona Cabazitaxel: 25 mg/ m2 IV a cada 21 dias Prednisona: 10 mg VO/dia Vinorelbina + Hidrocortisona Vinorelbina: 30 mg/ m2 Dias 1 e 8 a cada 21 dias. + Hidrocortisona: 40 mg VO dia, uso contnuo. Abiraterona + Prednisona Abiraterona: 1g VO dia + Prednisona: 5 mg VO 2 x dia, uso contnuo.
Ref. (16)
Ref. (17)
Ref. (18)
Ref. (19)
1. Eisenberger MA, et al. Prognostic factors in stage D2 prostate cancer: important implications for future trials; results of a cooperative intergroup study (INT.0036). The national cancer institute intergroup study #0036. Semin oncol 1994;21:613-619. 2. Jurincic CD, et al. Combined treatment (goserelin plis flutamide) versus monotherapy (goserelin alone) in advanced prostate cancer: a randomized study. Semin oncol 1991;18 (Suppl 6):21-25. 3. Tannock IF, de Wit R, Berry WR, et al: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351:1502-1512, 2004. 4. Copur MS, et al. Weekly docetaxel and estramustine in patients
85
with hormone-refractory prostate cancer. Semin oncol 2001;28:16-21. 5. Tannock IF, et al. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormoneresistant prostate cancer: a Canadian randomized trial with palliative end points. J clin oncol 1996:14:1756-1764. 6. Dreicer R. Chemotherapy for advanced prostate cancer: docetaxel and beyond. Hematol oncol clin north Am 2006;20:935-926. 7. Dijkman GA, et al. A randomized trial comparing the safety and efficacy oh the zoladex 10.8mg de pot, administered every twelve weeks, to that of the zoladex 3.6mg depot, administered every four weeks, in patients with advanced prostate cancer. The Dutch South East Cooperative Urological Group. Eur Urol 1995;27:43-46. 8. The Leuprolide Study Group. Leuporlide versus diethylstilbestrol for metastatic prostate cancer. N Engk J Med 1984;311:1281-1286. Sharifi R, et al. Leuprolide acetate 22.5 mg 12-week depot formulation in the treatment of patients with advanced prostate cancer. Clin Ther 1996;18:647-657. 9. Schellhammer PF, et al. Clinical benefits of bicalutamide compared with flutamide in combined androgen clockade for patients with advanced prostatic carcinoma: final report of a double blind, randomized, multicenter trial. Urology 1997;50:330-336. 10. Mc Leod DG, et al. The use of flutamide in hormone refractory metastatic prostate cancer. Cancer 1993;72:38703873. 11. Janknegt RA, et al. Orchiectomy and nilutamine or placebo as treatment of metastatic prostatic cancer in a multinational doubleblind randomized trial. J Urol 1993;149:77-82. 12. Tannock IF, et al. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-
86
resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol 1996:14:1756-1764. 13. Johnson DE, et al. Ketoconazole therapy for hormonally refractive metastatic prostate cancer Erology 1988;31:132134. 14. Roth BJ. et al. Taxol in advanced, hormone-refractory carcinoma of the rrw.ate. A phase II trial of the Eastern Cooperative Oncoiogy Group cancer 1993;2:245-2260. 15. Ahmed S, et al. Feasibility of weekly one hour paclitaxel in hormone refractory prostate cancer (HRPC): a preliminary report of a phase II trial. Proc Am Soe Clin Oncol 1998; 17:325a. 16. Smith DC, Redman BG, Flaherty LE, Li L, et al. phase II trial of oral diethylstilbesterol as a secondline hormonal agent in advanced prostate cancer. Urology.1998;52:257-60. 17. Bono J. S. de, Oudard S, Ozguroglu M, et al. Cabazitaxel or mitoxantrone with prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel: Final results of a multinational phase III trial (TROPIC). J Clin Oncol. 2010. 28:15s (suppl; abstr 4508). 18. Abratt R. P , Brune D., Dimopoulos M. - A, et. Al. Randomised phase III study of intravenous vinorelbine plus hormone therapy versus hormone therapy alone in hormonerefractory prostate cancer. Ann Oncol. 2004;15(11): 16131621. 19. de Bono JS, Logothetis CJ, Molina A, et. al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011; 26;364(21):1995-2005.
87
Cncer de Testculo
PEB Bleomicina: 30 UI, IV D2, D9 e D16 Etoposide: 100 mg/m IV D1 ao D5 Cisplatina: 20 mg/m IV D1 ao D5 a cada 21 dias no total de 3 ou 4 ciclos Ref. (1) Carboplatina 1- 2 ciclos Carboplatina: AUC de 7 IV em 30 minutos a cada 3 semanas no total de 1 ou 2 ciclos Ref. (2) EP Etoposide: 100 mg/m IV D1 ao D5 Cisplatina: 20 mg/m IV D1 ao D5 a cada 21 dias no total de 4 ciclos Ref. (3) VeIP (regime de resgate) Vimblastina: 0,11 mg/kg IV D1 e D2 Ifosfamida: 1200 mg/m IV D1 ao D5 Cisplatina: 20 mg/m IV D1 ao D5 Mesna: 400 mg/m IV, administrado 15 minutos antes da primeira dose de ifosfamida, e ento 1200 mg/m/dia IV infuso contnua por 5 dias a cada 21 dias Ref. (4)
88
VIP (regime de resgate) Etoposide: 75 mg/m IV D1 ao D5 Ifosfamida: 1200 mg/m IV D1 ao D5 Cisplatina: 20 mg/m IV D1 ao D5 Mesna: 400 mg/m IV administrado 15 minutos antes na primeira dose de Ifosfamida, e ento 1200 mg/m/dia IV infuso contnua por 5 dias. Filgrastima: 300mcg SC por 5 dias a cada 21 dias Ref. (5) TIP (regime de resgate) Paclitaxel: 250 mg/m IV infuso contnua D1 Ifosfamida: 1200 mg/m IV durante 1 hora D2 ao D6 Cisplatina: 20 mg/m IV durante 1 hora D2 ao D6 Mesna: 400 mg/m IV 30 min antes, 4 e 8 horas aps Ifosfamida Filgrastima: 300 mcg/dia SC por 5 dias. a cada 21 dias Ref. (6) BEP Cisplatina 50 mg/m2 IV D1 e D2 Bleomicina 30 mg IV D2, D9 e D16 Etoposide 165 mg/m2/dia IV D1, D2 e D3 Ref. (7) CBOP/BEP (regime de resgate) Ciclo 1 e 2 (C-BOP) Cisplatina 50 mg/m2 IV D1 e D2 Vincristina 2mg IV D1 e D8 Bleomicina 15 mg IV D1 e D8 Cisplatina 40 mg/m2 IV Carboplatina AUC3 IV D8 Bleomicina 15 mg IV em infuso contnua D8 a D12
89
Ciclo 3 (BO) Vincristina 2mg IV D1 e D8 Bleomicina 15 mg IV D1 e D8 Ciclo 4, 5 e 6 (BEP modificado) Cisplatina 20 mg/m2/dia, D1 a D5 Etoposide 100mg/m2/dia, D1 a D5 Bleomicina 15 mg IV D1, D8 e D15 SEMANAS 1 a 4 2 ciclos de C-BOP SEMANAS 5 e 7 2 ciclos de BO SEMANAS 10, 13 e 17 3 ciclos de BEP modificado Ref. (8) 1. Williams SD, et al. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med 1987;316:1465-1440. 2. Oliver RT, Mason MD, Mead GM, von der Maase H, Rustin GJ, Joffe JK, et al. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Lancet 2005;366:293300. 3. Bosl G, et al. A randomized trial of etoposide + cisplatin versus vinblastine + bleomycin + cisplatin + cyclophosphamide + dactinomycin in patients with goodprognosis germ cell tumors. J Clin Oncol 1988;6:1231-1238. 4. Loehrer PJ, et al. Salvage therapy in recurrent germ cell cancer: ifosfamide and cisplatin plus either vinblastine or etoposide. Ann Intern Med 1988;109:540-546. 5. Loehrer PJ, et al. Salvage therapy in recurrent germ cell cancer: ifosfamide and cisplatin plus either vinblastine or etoposide. Ann Intern Med 1988;109:540-546. 6. Motzer R, Sheinfeld J, Mazumdar M et al. Paclitaxel, Ifosfamide, and Cisplatin Second-Line Therapy for Patients With Relapsed Testicular Germ Cell Cancer J Clin Oncol 2000:2413-2418.
90
Cncer de Pnis
TIP Paclitaxel: 175 mg/m2 IV D1 Cisplatina: 25 mg/ m2 IV D1-D3 Ifosfamida: 1200 mg/ m2 IV D1-D3 Mesna : 400 mg/ m2 IV hora 0,4 e 8 da Ifosfamida a cada 21 dias Ref. (1) Cisplatina + 5-Fluorouracil Cisplatina: 100 mg/m2 IV 2 5-Fluorouracil: 1000 mg/m IV Ref. (2)
D1 D1-D4 a cada 21 dias
1. Pagliaro Lance C., Williams Dallas L., Daliani, Danai. Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy for metastatic penile cancer:a phase II study. J Clin Oncol. 2010; 28: 3851-3857. 2. Shammas FV, Ous S, Fossa SD. Cisplatin and 5-fluorouracil in advanced cancer of the penis. J Urol 1992;147:630-2.
92
Cncer de Endomtrio
Carboplatina + Paclitaxel Carboplatina: AUC 5-7 Paclitaxel: 175mg/m2 a cada 21 dias Ref. (1) Adriamicina + Ciclofosfamida Doxorrubicina: 60mg/m2 Ciclofosfamida: 500mg/m2 a cada 21 dias Ref. (2) Adriamicina + Cisplatina Doxorrubicina: 50mg/m2 Cisplatina: 50mg/m2 a cada 21 dias Ref.(3) Adriamicina + Paclitaxel Doxorrubicina: 50mg/m2 Paclitaxel: 150mg/m2 a cada 21 dias Ref. (4) IV IV D1 D1
IV IV
D1 D1
IV IV
D1 D1
IV IV
D1 D1
Cisplatina + Doxorrubicina + Paclitaxel Cisplatina: 50mg/m2 IV 2 Doxorrubicina: 45mg/m IV Paclitaxel: 160mg/m2 IV Filgrastima: 5mcg/kg SC a cada 21 dias Ref. (5)
D1 D1 D2 D3-D12
93
CAP Ciclofosfamida: 500mg/m2 Doxorrubicina: 50mg/m2 Cisplatina: 500mg/m2 Ref. (6)
IV IV IV
Carboplatina + Doxorrubicina Lipossomal Carboplatina: AUC 5 IV D1 2 Doxo lipossomal: 40mg/m IV D1 a cada 28 dias Ref. (7) Doxorrubicina Doxorrubicina: 60mg/m2 IV Ref. (8) Paclitaxel Paclitaxel: 200mg/m2 IV Se RXT prvia: 175mg/m2 IV Ref. (9) Topotecano Topotecano: 1mg/m2/dia Se RXT prvia 0,8mg/m2/dia Ref. (10) Acetato de Megestrol Acetato de megestrol: 160mg Ref.(11) Tamoxifeno Tamoxifeno: 20mg Ref.(12)
D1 a cada 21 dias
D1 a cada 21 dias D1 a cada 21 dias
IV D1-D5 a cada 21 dias IV D1-D5 a cada 21 dias
VO
Contnuo
VO
Contnuo
94
Anastrozol Anastrozol: 1 mg/dia VO contnuo Ref. (13) Letrozol Letrozol: 2,5 mg VO dia contnuo Ref. (14) Ifosfamida Ifosfamida: 1200mg/m2 IV Mesna: 300 mg/m2 IV D1 a D5 concomitante, 4 e 8hs aps ifosfamida Ref. (15) Doxorrubicina lipossomal Doxorrubicina lipossomal: 40mg/m2 Ref. (16)
a cada 28 dias
IV
D1
28 dias
1. Hoskins, P.J., et al. Paclitaxel and carboplatin, alone or with irradiation, in advanced or recurrent endometrial cancer: a phase II study. J Clin Oncol, 2001. 19(20): p. 4048-53. 2. Thigpen, J.T., et al. A randomized comparison of doxorubicin alone versus doxorubicin plus cyclophosphamide in the management of advanced or recurrent endometrial carcinoma: A Gynecologic Oncology Group study. J Clin Oncol, 1994. 12(7): p. 1408-14. 3. Deppe, G., et al. Treatment of recurrent and metastatic endometrial carcinoma with cisplatin and doxorubicin. Eur J Gynaecol Oncol, 1994. 15(4): p. 263-6. 4. Fleming G. F., Filiaci V. L., Bentley R. C, et. al.Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a
95
Gynecologic Oncology Group study. Ann Oncol. 2004; 15(8): 1173-1178. 5. Fleming, G.F., et al. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol, 2004. 22(11): p. 2159-66. 6. Burke, T.W., et al. Postoperative adjuvant cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy in women with high-risk endometrial carcinoma. Gynecol Oncol, 1994. 55(1): p. 47-50. 7. Pignata, S., et al. A multicentre phase II study of carboplatin plus pegylated liposomal doxorubicin as first-line chemotherapy for patients with advanced or recurrent endometrial carcinoma: the END-1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) group. Br J Cancer, 2007. 96(11): p. 1639-43. 8. Muss, H.B., Chemotherapy of metastatic endometrial cancer. Semin Oncol, 1994. 21(1): p. 107-13. 9. Ball, H.G., Do we know the best therapy for early endometrial cancer? Gynecol Oncol, 1996. 60(2): p. 173-5. 10. Wadler, S., et al. Topotecan is an active agent in the first-line treatment of metastatic or recurrent endometrial carcinoma: Eastern Cooperative Oncology Group Study E3E93. J Clin Oncol, 2003. 21(11): p. 2110-4. 11. Thigpen, J.T., et al. Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. J Clin Oncol, 1999. 17(6): p. 1736-44. 12. Thigpen, T., et al. Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol, 2001. 19(2): p. 364-7. 13. Rose PG, Brunetto, VL, et al. A Phase II trial of Anastrozolein advanced recurrent or persistent endometrial carcinoma: A Gynecologic Oncology Group Study. Gynecologic Oncology,2000; 78, 212-216.
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14. Ma B B.Y, Oza A, et al. The activity of letrozole in patients with advanced or recurrent endometrial cancer and correlation with biological markers a study of the National Cancer Institute of Canada Clinical Trials Group, Intern J Gynecol Cancer 2004. 14(4):650 - 658. 15. Sutton GP, et al. A Phase II Gynecologic Oncology Group Trial of Ifosfamide and Mesna in Advanced or Recurrent Adenocarcinoma of the Endometrium. Gynecol Oncol. Ginecol Oncol 1996;63:25-7. 16. Homesley, HD, et. al. Phase II trial of liposomal doxorubicin at 40 mg/m2 every 4 weeks in endometrial carcinoma: A Gynecologic Oncology Group Study Gynecol Oncol 2005; 98:294-8.
97
Cncer de Colo Uterino

Cisplatina + Radioterapia Cisplatina: 40mg/m2 IV trmino da radioterapia Paclitaxel + Cisplatina Paclitaxel: 135mg/m2 IV Cisplatina: 75mg/m2 IV Ref. (9) D1 Semanal at Ref. (1)
D1 em infuso de 24 horas D1 a cada 21 dias
Cisplatina + Topotecano Cisplatina: 50mg/m2 Topotecano: 0,75mg/m2/dia Ref. (2) Cisplatina + 5-Fluorouracil Cisplatina: 75mg/m2 5-Fluorouracil: 1000mg/m2 Ref. (3)
IV D1 IV D1 a D3 a cada 21 dias
IV D1 IV D1 a D5 a cada 21 dias
Cisplatina + Vinorelbina Cisplatina: 80mg/m2 IV D1 Vinorelbina: 25mg/m2 IV D1, D8 Ref. (4) Cisplatina + Irinotecano Cisplatina: 60mg/m2 IV 2 Irinotecano: 60mg/m IV a cada 28 dias Docetaxel Docetaxel: 100mg/m2
a cada 21 dias
D1 D1, D8, D15 Ref. (5)
IV
D1 a cada 21 dias
98
Paclitaxel Paclitaxel: 175mg/m2 Ref. (6) Irinotecano Irinotecano: 125mg/m2 folga de 14 dias
IV
D1 a cada 21 dias
IV
D1, D8, D15, D22 com Ref. (7)
Topotecano Topotecano: 1,5mg/m2/dia IV Ref. (8)
D1 a D5 a cada 21 dias
Vinorelbina Vinorelbina: 30 mg/m2 IV semanalmente
Ref. (10)
Ifosfamida Ifosfamida: 1.200 mg/m2 ( com Mesna) IV D1 a D5 a cada 21 dias Ref. (11) Gencitabina Gencitabina: 800 mg/m2 IV D1, D8 e D15 a cada 28 dias Ref. (12) 1. Rose, P.G., et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med, 1999. 340(15): p. 1144-53. 2. Long, H.J., 3rd, et al. Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol, 2005. 23(21): p. 4626-33. 3. Whitney, C.W., et al. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol, 1999. 17(5): p. 1339-48.
99
4. Pignata, S., et al. Phase II study of cisplatin and vinorelbine as first-line chemotherapy in patients with carcinoma of the uterine cervix. J Clin Oncol, 1999. 17(3): p. 756-60. 5. Chitapanarux, I., et al. Phase II clinical study of irinotecan and cisplatin as first-line chemotherapy in metastatic or recurrent cervical cancer. Gynecol Oncol, 2003. 89(3): p. 402-7. 6. Thigpen, T., et al. The role of paclitaxel in the management of patients with carcinoma of the cervix. Semin Oncol, 1997. 24(1 Suppl 2): p. S2-41-S2-46. 7. Verschraegen, C.F., et al. Phase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix. J Clin Oncol, 1997. 15(2): p. 625-31. 8. Muderspach, L.I., et al. A Phase II study of topotecan in patients with squamous cell carcinoma of the cervix: a gynecologic oncology group study. Gynecol Oncol, 2001. 81(2): p. 213-5. 9. Piccart, M.J., et al. Randomized intergroup trial of cisplatinpaclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J Natl Cancer Inst, 2000. 92(9): p. 699-708. 10. Morris M, Brader KR, Levenback C, et al. Phase II study of vinorelbine in advanced and recurrent squamous cell carcinoma of the cervix. J Clin Oncol. 1998; 16:1094-1098. 11. Sutton GP, Blessing JA, McGuire WP, et al. Phase II trial of ifosfamide and mesna in patients with advanced or recurrent squamous carcinoma of the cervix who had never received chemotherapy: a gynecologic oncology group study. Am J Obstet Gynecol. 1993; 168:805-7. 12. Schilder RJ, Blessing JA, Morgan M, et al. Evaluation of gemcitabine in patients with squamous cell carcinoma of the cervix: A phase II study of the Gynecologic Oncology Group. Gynecol Oncol 76:204207, 2000.
100
Cncer de Mama
AC-D Adriamicina: 60 mg/m2 IV 2 Ciclofosfamida: 600 mg/m IV Docetaxel: 100mg/m2 IV a cada 21 dias X 4 ciclos OU Doxorrubicina: 60 mg/m2 IV Ciclofosfamida: 600 mg/m2 IV Docetaxel: 35mg/m2 IV semanal X 12 semanas AC-T Doxorrubicina: 60 mg/m2 IV Ciclofosfamida: 600 mg/m2 IV Paclitaxel: 175mg/m2 IV a cada 21 dias X 4 ciclos Doxorrubicina: 60 mg/m2 IV Ciclofosfamida: 600 mg/m2 IV Paclitaxel: 80mg/m2 IV semanal X 12 semanas TAC Doxorrubicina: 50 mg/m2 Ciclofosfamida: 500 mg/m2 Docetaxel: 75 mg/m2 Ciprofloxacina: 500mg Filgrastima: 300mcg a cada 21 dias X 6 ciclos Ref. (4, 5) D1 D1a cada 21 dias X 4 ciclos D1 aps 4 ciclos de AC Ref. (2, 3) D1 D1 a cada 21 dias X 4 ciclos D1 aps 4 ciclos de AC Ref. (1-3)
D1 D1 a cada 21 dias X 4 ciclos D1 aps 4 ciclos de AC Ref. (2) D1 D1 a cada 21 dias X 4 ciclos D1 aps 4 ciclos de AC Ref. (2, 3)
IV IV IV VO BID SC
D1 D1 D1 D5-D14 D2-D14
101
AC Doxorrubicina: 60 mg/m2 IV Ciclofosfamida: 600 mg/m2 IV Ref. (6-8) FAC 5-Fluorouracil: 500 mg/m2 IV Doxorrubicina: 50 mg/m2 IV Ciclofosfamida: 500 mg/m2 IV Ref. (9, 10)
D1 D1 a cada 21 dias X 4 ciclos
D1 D1 D1 a cada 21 dias X 6 ciclos
CMF oral Ciclofosfamida: 100 mg/m2 VO D1 a D 14 Methotrexate: 40 mg/m2 IV D1 2 5-Fluorouracil: 600 mg/m IV D1 a cada 28 dias X 6 ciclos Ref. (11) CMF Ciclofosfamida: 600mg/m2 IV Methotrexate: 40 mg/m2 IV 5-Fluorouracil: 600 mg/m2 IV Ref. (12) CMF Ciclofosfamida: 600mg/m2 IV Methotrexate: 40 mg/m2 IV 5-Fluorouracil: 600 mg/m2 IV ciclos TC Docetaxel: 75mg/m2 IV 2 Ciclofosfamida: 600 mg/m IV Ref.(13)
D1 e D8 D1 e D8 D1 e D8 a cada 28 dias X 6
102
FEC 100 5-Fluorouracil: 500mg/m2 IV Epirrubicina: 100 mg/m2 IV Ciclofosfamida: 500 mg/m2 IV Ref. (14-16) FEC 100- Docetaxel 5-Fluorouracil: 500mg/m2 IV Epirrubicina: 100 mg/m2 IV Ciclofosfamida: 500 mg/m2 IV Docetaxel: 100mg/ m2 IV a cada 21 dias X 3 ciclos TCH Docetaxel: 75mg/m2 Carboplatina: AUC 6 Trastuzumabe: 8mg/kg Trastuzumabe: 6mg/kg
D1 D1 D1 D1 aps FEC Ref. (17)
IV IV IV IV
D1 D1 a cada 21 dias X 6 ciclos D1 ATAQUE D1 a cada 21 dias por 1 ano
AC-TH Doxorrubicina: 60mg/m2 IV Ciclofosfamida: 600mg/m2 IV Paclitaxel: 80mg/m2 IV semanal X 12 semanas Trastuzumabe: 4mg/kg IV Trastuzumabe: 2mg/kg IV Ref.(18)
D1 D1 a cada 21 dias X 4 ciclos D1 aps 4 ciclos de AC D1 D1 ATAQUE semanal por 1 ano
AC-TH Doxorrubicina: 60mg/m2 IV D1 Ciclofosfamida: 600mg/m2 IV D1 a cada 21 dias X 4 ciclos 2 Paclitaxel: 175mg/m IV D1 aps 4 ciclos de AC a cada 21 dias X 4 ciclos Trastuzumabe: 4mg/kg IV D1 ATAQUE Trastuzumabe: 2mg/kg IV D1 semanal por 1 ano Ref.(18)
103
AC-TH Doxorrubicina: 60mg/m2 IV Ciclofosfamida: 600mg/m2 IV Paclitaxel: 80mg/m2 IV semanal X 12 semanas Trastuzumabe: 4mg/kg IV Trastuzumabe: 2mg/kg IV DH-FEC Docetaxel: 100mg/m2 IV Trastuzumabe: 4mg/kg IV Trastuzumabe: 2mg/kg IV 5-Fluourouracil: 600mg/m2IV Epirrubicina: 60mg/m2 IV 2 Ciclofosfamida: 600mg/m IV a cada 21 dias X 4 ciclos Ref. (19) VH-FEC Vinorelbina: 25g/m2 IV Trastuzumabe: 4mg/kg IV Trastuzumabe: 2mg/kg IV 5-Fluourouracil: 600mg/m2IV Epirrubicina: 60mg/m2 IV 2 Ciclofosfamida: 600mg/m IV a cada 21 dias X 4 ciclos AD Doxorrubicina: 50mg/m2 IV Docetaxel: 75mg/m2 IV a cada 21 dias Ref. (8)
D1 D1 a cada 21 dias X 4 ciclos D1 aps 4 ciclos de AC D1 D1 ATAQUE semanal por 1 ano
D1 a cada 21 dias X 4 ciclos D1 ATAQUE D1 semanal por 9 semanas D1 D1 D1 aps 4 ciclos de DH
D1 a cada 21 dias X 4 ciclos D1 ATAQUE D1 semanal por 9 semanas
D1 aps 4 ciclos de DH Ref. (19)
D1 D1
104
AT Doxorrubicina: 60 mg/m2 IV Paclitaxel: 175 mg/m2 IV Ref. (20)
D1 D1
a cada 21 dias
Docetaxel + Capecitabina Docetaxel: 75 mg/m2 IV D1 a cada 21 dias Capecitabina: 1250mg/m2 VO BID D1 a D14 a cada 21 dias Ref. (21) Vinorelbina + Capecitabina Vinorelbina: 25 mg/m2 IV D1 e D8 a cada 21 dias Capecitabina: 1000 mg/m2 VO BID D1 a D 14 a cada 21 dias Ref. (22, 23) Gencitabina + Capecitabina Gencitabina: 2000 mg/m2 IV D1 a cada 21 dias 2 Capecitabina: 1250mg/m VO BID D1 a D 14 a cada 21 dias Ref. (24) OU Gencitabina: 800mg/m2 Capecitabina 750mg/m2 Ref. (25) IV D1 e D8 a cada 21 dias VO BID D1 a D14 a cada 21 dias
Vinorelbina + Gencitabina Vinorelbina 25mg/m2 IV Gencitabina: 1000mg/m2 IV Ref. (26)
105
Cisplatina + Gencitabina Cisplatina: 30 mg/m2 IV D1 e D8 2 Gencitabina: 750 mg/m IV D1 e D8 a cada 21 dias Ref. (27) Doxorrubicina Doxorrubicina: 60 mg/m2 IV D1 a cada 21 dias Ref. (28) Epirrubicina Epirrubicina: 75mg/m2 Ref. (29) Paclitaxel Paclitaxel: 175mg/m2 Ref. (28, 30) OU Paclitaxel: 90mg/m2 Ref. (31) Docetaxel Docetaxel: 100mg/m2 Ref. (32) OU Docetaxel: 40mg/m2 IV D1, D8, D15, D22, D29, D36 Ref. (33) IV D1 a cada 7 dias
IV D1 a cada 21 dias
com 14 dias de folga
Capecitabina Capecitabina: 1250mg/m2 VO BID D1 a D14 a cada 21 dias Ref. (34)
106
Vinorelbina Vinorelbina: 30mg/m2 Ref. (35)
IV D1 e D8 a cada 21 dias
Doxorrubicina Lipossomal Doxo lipossomal: 40mg/m2 IV D1 a cada 28 dias Gencitabina Gencitabina: 750mg/m2 Ref. (37) Trastuzumabe Trastuzumabe: 8mg/kg Trastuzumabe: 6mg/kg Ref. (38) OU Trastuzumabe: 4mg/kg Trastuzumabe: 2mg/kg Ref. (39) IV IV D1 D1
Ref. (36)
IV
D1, D8, D15 a cada 28 dias
IV IV
D1 D1
ATAQUE a cada 21 dias
ATAQUE a cada 7 dias
Paclitaxel + Trastuzumabe Paclitaxel: 175mg/m2 IV Trastuzumabe: 4mg/kg IV Trastuzumabe: 2mg/kg IV subsequente OU Paclitaxel: 90mg/m2 Trastuzumabe: 4mg/kg Trastuzumabe: 2mg/kg subsequente Ref. (41) IV IV IV
D1 D1 D1
a cada 21 dias ATAQUE a cada 7 dias Ref. (40)
D1 D1 D1
a cada 7 dias ATAQUE a cada 7 dias
107
Docetaxel + Trastuzumabe Docetaxel: 100mg/m2 IV Trastuzumabe: 4mg/kg IV Trastuzumabe: 2mg/kg IV subsequente Ref. (42) OU Docetaxel: 35mg/m2 Trastuzumabe: 4mg/kg Trastuzumabe: 2mg/kg subsequente Ref. (43) IV IV IV
D1 a cada 21 dias D1 ATAQUE D1 a cada 7 dias
Vinorelbina + Trastuzumabe Vinorelbina: 25mg/m2 IV Trastuzumabe: 4mg/kg IV Trastuzumabe: 2mg/kg IV subsequente Ref. (44) Gencitabina + Trastuzumabe Gencitabina: 1200mg/m2 IV a cada 21 dias Trastuzumabe: 4mg/kg IV Trastuzumabe: 2mg/kg IV subsequente Ref. (45)
D1 e D8 D1 D1 ATAQUE a cada 7 dias
Vinorelbina Oral Vinorelbina: 80mg/m2 D1 semanal aps 3 administraes com dose de 60mg/m2 semanal para testar mielossensibilidade Ref. (71)
108
Gencitabina + Paclitaxel Gencitabina: 1250mg/m2 IV D1 e D8 Paclitaxel: 175mg/m2 IV D1 a cada 21 dias Ref. (46, 47) Gencitabina + Docetaxel Gencitabina: 1000mg/m2 IV Docetaxel: 75mg/m2 IV Ref. (48) Gencitabina + Vinorelbina Gencitabina: 1200mg/m2 IV Vinorelbina : 30mg/m2 IV Ref. (49) Lapatinibe + Capecitabina Lapatinibe: 1250mg Capecitabina : 2000mg/m2 a cada 21 dias Ref. (50)
D1 e D8 D1 a cada 21 dias
D1 e D8 D1 e D8 a cada 21 dias
VO/dia contnuo VO D1 a D14
Lapatinibe + Trastuzumabe Lapatinibe: 1250mg VO/dia contnuo Trastuzumabe: 4mg/kg IV D1 ATAQUE Trastuzumabe: 2mg/kg IV D1 a cada 7 dias Tamoxifeno Tamoxifeno: 20mg anos/indefinido Ref. (51, 52) Anastrozol Anastrozol: 1mg VO Ref. (53-55)
VO
Diariamente
Diariamente
5 anos/indefinido
109
Letrozol Letrozol: 2,5mg VO Ref. (56, 57)
Diariamente
indefinido
Exemestano Exemestano: 25mg VO Diariamente Ref. (58, 59) Tamoxifeno + Letrozol Tamoxifeno: 20mg VO Letrozol: 2,5mg VO aps trmino Tamoxifeno Ref. (60) Tamoxifeno + Exemestano Tamoxifeno: 20mg VO Exemestano: 25mg VO completar 5 anos Ref. (61) Fulvestranto Fulvestranto: 250mg Ref. (62) Megestrol Megestrol: 160 mg VO Ref. (63) Toremifeno Toremifeno: 60mg VO Ref. (64)
indefinido
Diariamente Diariamente
5 anos 5 anos
Diariamente Diariamente
2-3 anos At
IM
D1
a cada 28 dias
Diariamente
indefinido
Diariamente
indefinido
Anlogo LHRH+ Tamoxifeno LHRH: -------- IM ou SCD1 Tamoxifeno: 20mg VO
a cada 28 dias Contnuo
Ref. (65)
110
Analogo LHRH+ Anastrozol LHRH: -------- IM ou SCD1 Anastrozol 1mg VO
a cada 28 dias Contnuo
Dose densa AC ! T Doxorrubicina: 60 mg/m IV no D1 Ciclofosfamida: 600 mg/m IV no D1 Filgrastima: 300mcg SC do D2 ao D12 a cada 14 dias no total de 4 ciclos. seguido por Paclitaxel: 175 mg/m IV no D1 a cada 14 dias por 4 ciclos Filgrastima: 300mcg SC do D2 ao D12 OU Paclitaxel: 80 mg/m IV semanalmente por 12 semanas Ref. (66) ATH ! TH ! CMFH (NOAH trial) Doxorrubicina: 60 mg/m IV no D1 Paclitaxel: 175mg/m IV D1 a cada 3 semanas X 3 ciclos Seguido de: Paclitaxel: 175 mg/m IV D1 X 4 ciclos Seguido de: Ciclofosfamida: 600mg/m2 IV D1 e D8 Methotrexate: 40mg/m2 IV D1 e D8 5-Fluorouracil: 600mg/m2 D1 e D8 Repetir CMF a cada 28 dias por 3 ciclos. Trastuzumabe concomitante com toda a Quimioterapia (dose ataque 8mg/kg seguido de dose de manuteno de 6mg/kg a cada 3 semanas at completar 1 ano de terapia). Ref. (67)
111
Paclitaxel + Bevacizumabe (ECOG 2100) Paclitaxel: 90 mg/m2 IV no D1, D8 e D15 a cada 4 semanas, associado a Bevacizumabe: 10mg/kg IV a cada 2 semanas. Ref. (68) Docetaxel + Bevacizumabe (AVADO) Docetaxel: 100mg/m2 IV no D1 a cada 3 semanas. Bevacizumabe: 15mg/kg IV no D1 a cada 3 semanas. Ref. (69) Capecitabina + Bevacizumabe (RIBBON 1) Capecitabina: 1000mg/m2 VO BID por 14 dias a cada 21 dias. Bevacizumabe: 15mg/kg IV no D1 a cada 3 semanas. Ref. (70) 1. Bear, H.D., et al. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol, 2003. 21(22): p. 4165-74. 2. Sparano, J.A., et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med, 2008. 358(16): p. 1663-71. 3. De Laurentiis, M., et al. Taxane-based combinations as adjuvant chemotherapy of early breast cancer: a meta-analysis of randomized trials. J Clin Oncol, 2008. 26(1): p. 44-53. 4. Martin, M., et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med, 2005. 352(22): p. 2302-13. 5. Mackey, J., Proc.ASCO, 2002. 21(abstract137). 6. Fisher, B., et al. Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National
112
Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol, 1990. 8(9): p. 1483-96. 7. Fisher, B., et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol, 1998. 16(8): p. 2672-85. 8. Nabholtz, J.M., et al. Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter, phase III trial. J Clin Oncol, 2003. 21(6): p. 968-75. 9. Martin, M., et al. Doxorubicin in combination with fluorouracil and cyclophosphamide (i.v. FAC regimen, day 1, 21) versus methotrexate in combination with fluorouracil and cyclophosphamide (i.v. CMF regimen, day 1, 21) as adjuvant chemotherapy for operable breast cancer: a study by the GEICAM group. Ann Oncol, 2003. 14(6): p. 833-42. 10. Stewart, D.J., et al. Cyclophosphamide and fluorouracil combined with mitoxantrone versus doxorubicin for breast cancer: superiority of doxorubicin. J Clin Oncol, 1997. 15(5): p. 1897-905. 11. Bonadonna, G., et al. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med, 1976. 294(8): p. 405-10. 12. Pritchard, K.I., et al. Randomized trial of cyclophosphamide, methotrexate, and fluorouracil chemotherapy added to tamoxifen as adjuvant therapy in postmenopausal women with node-positive estrogen and/or progesterone receptorpositive breast cancer: a report of the National Cancer Institute of Canada Clinical Trials Group. Breast Cancer Site Group. J Clin Oncol, 1997. 15(6): p. 2302-11. 13. Jones, S.E., et al. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol, 2006. 24(34): p. 5381-7. 14. Coombes, R.C., et al. Adjuvant cyclophosphamide,
113
methotrexate, and fluorouracil versus fluorouracil, epirubicin, and cyclophosphamide chemotherapy in premenopausal women with axillary node-positive operable breast cancer: results of a randomized trial. The International Collaborative Cancer Group. J Clin Oncol, 1996. 14(1): p. 35-45. 15. Benefit of a high-dose epirubicin regimen in adjuvant chemotherapy for node-positive breast cancer patients with poor prognostic factors: 5-year follow-up results of French Adjuvant Study Group 05 randomized trial. J Clin Oncol, 2001. 19(3): p. 602-11. 16. Epirubicin-based chemotherapy in metastatic breast cancer patients: role of dose-intensity and duration of treatment. J Clin Oncol, 2000. 18(17): p. 3115-24. 17. Roche, H., et al. Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial. J Clin Oncol, 2006. 24(36): p. 5664-71. 18. Romond, E.H., et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med, 2005. 353(16): p. 1673-84. 19. Joensuu, H., et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med, 2006. 354(8): p. 809-20. 20. Biganzoli, L., et al. Doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as first-line chemotherapy in metastatic breast cancer: The European Organization for Research and Treatment of Cancer 10961 Multicenter Phase III Trial. J Clin Oncol, 2002. 20(14): p. 3114-21. 21. O'Shaughnessy, J., et al. Superior survival with capecitabine plus docetaxel combination therapy in anthracyclinepretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol, 2002. 20(12): p. 2812-23. 22. Biganzoli, L., M. Martin, and C. Twelves, Moving forward with capecitabine: a glimpse of the future. Oncologist, 2002. 7 Suppl 6: p. 29-35.
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23. Welt, A., et al. Phase I/II study of capecitabine and vinorelbine in pretreated patients with metastatic breast cancer. Ann Oncol, 2005. 16(1): p. 64-9. 24. Andres, R., et al. Gemcitabine/capecitabine in patients with metastatic breast cancer pretreated with anthracyclines and taxanes. Clin Breast Cancer, 2005. 6(2): p. 158-62. 25. Abstracts of the 27th Annual San Antonio Breast Cancer Symposium. December 8-11, 2004, San Antonio, Texas, USA. Breast Cancer Res Treat, 2004. 88 Suppl 1: p. S1-265. 26. Stathopoulos, G.P., et al. Phase II trial of biweekly administration of vinorelbine and gemcitabine in pretreated advanced breast cancer. J Clin Oncol, 2002. 20(1): p. 37-41. 27. Nagourney, R.A., et al. Gemcitabine plus cisplatin repeating doublet therapy in previously treated, relapsed breast cancer patients. J Clin Oncol, 2000. 18(11): p. 2245-9. 28. Sledge, G.W., et al. Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as frontline chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol, 2003. 21(4): p. 588-92. 29. A prospective randomized trial comparing epirubicin monochemotherapy to two fluorouracil, cyclophosphamide, and epirubicin regimens differing in epirubicin dose in advanced breast cancer patients. The French Epirubicin Study Group. J Clin Oncol, 1991. 9(2): p. 305-12. 30. Seidman, A.D., et al. Phase II trial of paclitaxel by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer. J Clin Oncol, 1995. 13(10): p. 2575-81. 31. Seidman, A.D., et al. Dose-dense therapy with weekly 1hour paclitaxel infusions in the treatment of metastatic breast cancer. J Clin Oncol, 1998. 16(10): p. 3353-61. 32. Nabholtz, J.M., et al. Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. 304 Study Group. J Clin Oncol, 1999. 17(5): p. 1413-24.
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33. Burstein, H.J., et al. Docetaxel administered on a weekly basis for metastatic breast cancer. J Clin Oncol, 2000. 18(6): p. 1212-9. 34. Blum, J.L., et al. Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer. J Clin Oncol, 1999. 17(2): p. 485-93. 35. Weber, B.L., et al. Intravenous vinorelbine as first-line and second-line therapy in advanced breast cancer. J Clin Oncol, 1995. 13(11): p. 2722-30. 36. Al-Batran, S.E., et al. Reduced incidence of severe palmarplantar erythrodysesthesia and mucositis in a prospective multicenter phase II trial with pegylated liposomal doxorubicin at 40 mg/m2 every 4 weeks in previously treated patients with metastatic breast cancer. Oncology, 2006. 70(2): p. 141-6. 37. Carmichael, J., et al. Advanced breast cancer: a phase II trial with gemcitabine. J Clin Oncol, 1995. 13(11): p. 2731-6. 38. Baselga, J., et al. Phase II study of efficacy, safety, and pharmacokinetics of trastuzumab monotherapy administered on a 3-weekly schedule. J Clin Oncol, 2005. 23(10): p. 2162-71. 39. Baselga, J., et al. Phase II study of weekly intravenous trastuzumab (Herceptin) in patients with HER2/neuoverexpressing metastatic breast cancer. Semin Oncol, 1999. 26(4 Suppl 12): p. 78-83. 40. Slamon, D.J., et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med, 2001. 344(11): p. 783-92. 41. Seidman, A.D., et al. Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification. J Clin Oncol, 2001. 19(10): p. 2587-95. 42. Marty, M., et al. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2positive metastatic breast cancer administered as first-line
116
treatment: the M77001 study group. J Clin Oncol, 2005. 23(19): p. 4265-74. 43. Esteva, F.J., et al. Phase II study of weekly docetaxel and trastuzumab for patients with HER-2-overexpressing metastatic breast cancer. J Clin Oncol, 2002. 20(7): p. 1800-8. 44. Burstein, H.J., et al. Clinical activity of trastuzumab and vinorelbine in women with HER2-overexpressing metastatic breast cancer. J Clin Oncol, 2001. 19(10): p. 2722-30. 45. O'Shaughnessy, J.A., et al. Phase II study of trastuzumab plus gemcitabine in chemotherapy-pretreated patients with metastatic breast cancer. Clin Breast Cancer, 2004. 5(2): p. 142-7. 46. O'Shaughnessy, J., Gemcitabine combination chemotherapy in metastatic breast cancer: phase II experience. Oncology (Williston Park), 2003. 17(12 Suppl 14): p. 15-21. 47. Albain, K.S., et al. Gemcitabine plus Paclitaxel versus Paclitaxel monotherapy in patients with metastatic breast cancer and prior anthracycline treatment. J Clin Oncol, 2008. 26(24): p. 3950-7. 48. Chan, S., et al. Phase III study of gemcitabine plus docetaxel compared with capecitabine plus docetaxel for anthracycline-pretreated patients with metastatic breast cancer. J Clin Oncol, 2009. 27(11): p. 1753-60. 49. Martin, M., et al. Gemcitabine plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer previously treated with anthracyclines and taxanes: final results of the phase III Spanish Breast Cancer Research Group (GEICAM) trial. Lancet Oncol, 2007. 8(3): p. 219-25. 50. Geyer, C.E., et al. Lapatinib plus capecitabine for HER2positive advanced breast cancer. N Engl J Med, 2006. 355(26): p. 2733-43. 51. Fisher, B., et al. Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer. J Natl Cancer Inst, 1997. 89(22): p. 1673-82. 52. Jaiyesimi, I.A., et al. Use of tamoxifen for breast cancer:
117
twenty-eight years later. J Clin Oncol, 1995. 13(2): p. 513-29. 53. Howell, A., Adjuvant aromatase inhibitors for breast cancer. Lancet, 2005. 366(9484): p. 431-3. 54. Buzdar, A.U., P.V. Plourde, and G.N. Hortobagyi, Aromatase inhibitors in metastatic breast cancer. Semin Oncol, 1996. 23(4 Suppl 9): p. 28-32. 55. Nabholtz, J.M., et al. Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. J Clin Oncol, 2000. 18(22): p. 3758-67. 56. Dombernowsky, P., et al. Letrozole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate. J Clin Oncol, 1998. 16(2): p. 453-61. 57. Mouridsen, H., et al. Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol, 2001. 19(10): p. 2596-606. 58. Lonning, P.E., Exemestane in breast cancer: current status and future directions. Clin Breast Cancer, 2000. 1 Suppl 1: p. S28-33. 59. Paridaens, R.J., et al. Phase III study comparing exemestane with tamoxifen as first-line hormonal treatment of metastatic breast cancer in postmenopausal women: the European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group. J Clin Oncol, 2008. 26(30): p. 4883-90. 60. Goss, P.E., et al. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptorpositive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst, 2005. 97(17): p. 1262-71. 61. Coombes, R.C., et al. A randomized trial of exemestane after
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two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med, 2004. 350(11): p. 1081-92. 62. Howell, A., Future use of selective estrogen receptor modulators and aromatase inhibitors. Clin Cancer Res, 2001. 7(12 Suppl): p. 4402s-4410s; discussion 4411s-4412s. 63. Kimmick, G.G. and H.B. Muss, Endocrine therapy in metastatic breast cancer. Cancer Treat Res, 1998. 94: p. 231-54. 64. Hayes, D.F., et al. Randomized comparison of tamoxifen and two separate doses of toremifene in postmenopausal patients with metastatic breast cancer. J Clin Oncol, 1995. 13(10): p. 2556-66. 65. Klijn, J.G., et al. Combined tamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: a meta-analysis of four randomized trials. J Clin Oncol, 2001. 19(2): p. 343-53. 66. Citron ML et al. Randomized Trial of Dose-Dense Versus Conventionally Scheduled and Sequential Versus Concurrent Combination Chemotherapy as Postoperative Adjuvant Treatment of Node-Positive Primary Breast Cancer: First Report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741 J Clin Oncol 2003;21(8):1481. 67. Gianni K, Ejermann W, Semiglazov V, et al. Neoadjuvant chemotherapy with trastuzumab followed byadjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlledsuperiority trial with a parallel HER2-negative cohort. Lancet 2010: 375; 377-384. 68. Miller K, Wang M, Gralow J, et al. A randomized phase III trial of paclitaxel versus paclitaxel plus bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer: a trial coordinated by the Eastern Cooperative Oncology Group (E2100). Breast Cancer Res Treat. 2005;94(suppl 1):S6. Abstract 3.
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69. Miles DW, Chan A, Romieu G, et al. Randomised, doubleblind, placebo controlled, phase III study of bevacizumab (BV) with docetaxel (D) or D with placebo (PL) as 1st line therapy for patients with locally recurrent or metastatic breast cancer (mBC): AVADO. J Clin Oncol 2008: 26;18S. 70. Robert NJ, Dieras V, Glaspy J, et al. RIBBON-1: Randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab (B) for first-line treatment of HER2-negative locally recurrent or metastatic breast cancer (MBC). J Clin Oncol 2009: 27;15s (suppl; abstr 1005). 71. Freyer, T. Phase II Study of Oral Vinorelbine in First-Line Advanced Breast Cancer Chemotherapy. JCO Jan 1, 2003:35-40.
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Metstases sseas e/ou Hipercalcemia Maligna

Denosumabe: 120 mg SC D1 a cada 30 dias Ref. (1) OU Pamidronato: 90mg Ref. (2) OU cido zoledrnico: 4 mg Ref. (3) IV D1 a cada 21 a 28 dias IV D1 a cada 28 dias
1. Stopeck Alison T., Lipton Allan, Body Jean-Jacques, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clinc Oncol. 2010; 28: 5132-5139. 2. Berenson JR, Hillner BE, Kyle RA, et al. American Society of Clinical Oncology clinical practice guidelines: The role of bisphosphonates in multiple myeloma. J Clin Oncol 2002 Sep 1;20(17): 3719-36. 3. Migliorati Cesar A, Siegel Michael A, Elting Linda S. Bisphosphonate-associated osteonecrosis: a long-term complication of bisphosphonate treatment. Lancet Oncol. 2006; 7: 508-514.
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Cncer de Ovrio (Epitelial)

Ciclofosfamida + Carboplatina Ciclofosfamida: 600mg/m2 IV Carboplatina: 300mg/m2 IV Ref. (1) Ciclofosfamida + Cisplatina Ciclofosfamida: 600mg/m2 IV IV Cisplatina: 100mg/m2 Ref. (2) Cisplatina + Paclitaxel Cisplatina: 75mg/m2 Paclitaxel: 135mg/m2 a cada 21 dias X 6 ciclos Ref. (3) OU Paclitaxel: 175mg/m2 IV D1 a cada 21 dias X 6 ciclos D1 D1 a cada 28 dias X 6 ciclos
IV IV
D1 D1 em 24 horas de infuso
Carboplatina + Paclitaxel Carboplatina: AUC 5 a 7 IV D1 Paclitaxel: 175mg/m2 IV D1 a cada 21 dias X 6 ciclos Ref. (4) Carboplatina + Docetaxel Carboplatina: AUC 6 IV D1 2 Docetaxel: 60mg/m IV D1 a cada 21 dias X 6 ciclos Ref. (5)
122
Cisplatina + Gencitabina Cisplatina: 30mg/m2 IV D1 e D8 Gencitabina: 750mg/m2 IV D1 e D8 Ref. (6)
a cada 21 dias X 6 ciclos
Doxorrubicina Lipossomal Doxo Lipossomal: 40-50mg/m2 IV D1 a cada 28 dias Ref. (7-9) Gencitabina Gencitabina: 1000mg/m2 IV 21 dias Ref. (9) Paclitaxel Paclitaxel: 135-170mg/m2 IV Ref. (10) OU Paclitaxel: 80mg/m2 Topotecano Topotecano: 1,5mg/m2 Ref. (11) IV D1, D8 e D15 a cada 28 dias
D1, D8, D15
cada
D1 a cada 21 dias
IV
D1 a D5 a cada 21 dias
Topotecano: 2,5 a 4mg/m2 Ref. (12) Etoposide Etoposide: 50mg/m2/dia VO 28 dias Ref. (13)
IV
D1 a D21
cada
123
Carboplatina Carboplatina: AUC 6 Ref. (14) Vinorelbina Vinorelbina: 25mg/m2 Ref. (15) Tamoxifeno Tamoxifeno: 20mg Ref. (16)
IV
D1
a cada 21 dias
IV
VO
Contnuo
Quimioterapia intraperitonial (estgio III) Paclitaxel: 135 mg/m2 IV em 24h D1 2 Cisplatina: 100 mg/m IP D2 2 Paclitaxel: 60 mg/m IP D8 a cada 21 dias por 6 ciclos Ref. (18) Docetaxel Docetaxel: 100mg/m2 Ref. (19)
IV
D1
21 dias
Oxaliplatina Oxaliplatina: 100 mg/m2 IV Ref. (20)
D1
21 dias
TIP Paclitaxel: 250 mg/m2 em 24 horas IV D1 2 Ifosfamida: 1.200 mg/m IV D2 D6 Mesna : 400 mg/m2 IV nas horas 0,4 e 8 da Ifosfamida D2-D6 Cisplatina: 20 mg/m2 IV D2-D6 a cada 21 dias. Ref. (21)
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VeIP Vinblastina: 0,1 mg/kg IV D1-D2 2 Ifosfamida: 1,200 mg/m IV D1 D5 Mesna : 400 mg/m2 IV nas horas 0,4 e 8 da Ifosfamida D1-D5 Cisplatina: 20 mg/m2 IV D1-D5 Ref. (22)
Cncer de Ovrio (Tumor de Clulas Germinativas)

BEP Cisplatina: 20mg/m2 IV D1-D5 2 Etoposide: 100mg/m IV D1-D5 Bleomicina: 30UI IV D2, D9,D16 a cada 21 dias Ref. (17) 1. Swenerton, K., et al. Cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in advanced ovarian cancer: a randomized phase III study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol, 1992. 10(5): p. 718-26. 2. Alberts, D.S., et al. Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer. J Clin Oncol, 1992. 10(5): p. 706-17. 3. McGuire, W.P., et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med, 1996. 334(1): p. 1-6. 4. Ozols, R.F., Combination regimens of paclitaxel and the platinum drugs as first-line regimens for ovarian cancer. Semin Oncol, 1995. 22(6 Suppl 15): p. 1-6. 5. Markman, M., et al. Combination chemotherapy with carboplatin and docetaxel in the treatment of cancers of the ovary and fallopian tube and primary carcinoma of the peritoneum. J Clin Oncol, 2001. 19(7): p. 1901-5.
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6. Nagourney, R.A., et al. Phase II trial of gemcitabine plus cisplatin repeating doublet therapy in previously treated, relapsed ovarian cancer patients. Gynecol Oncol, 2003. 88(1): p. 35-9. 7. Gordon, A.N., et al. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol, 2001. 19(14): p. 3312-22. 8. Rose, P.G., et al. Liposomal doxorubicin in ovarian, peritoneal, and tubal carcinoma: a retrospective comparative study of single-agent dosages. Gynecol Oncol, 2001. 82(2): p. 323-8. 9. Ferrandina, G., et al. Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer. J Clin Oncol, 2008. 26(6): p. 890-6. 10. McGuire, W.P., et al. Taxol: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. Ann Intern Med, 1989. 111(4): p. 273-9. 11. Kudelka, A.P., et al. Phase II study of intravenous topotecan as a 5-day infusion for refractory epithelial ovarian carcinoma. J Clin Oncol, 1996. 14(5): p. 1552-7. 12. Bhoola, S.M., et al. Retrospective analysis of weekly topotecan as salvage therapy in relapsed ovarian cancer. Gynecol Oncol, 2004. 95(3): p. 564-9. 13. Ozols, R.F., Oral etoposide for the treatment of recurrent ovarian cancer. Drugs, 1999. 58 Suppl 3: p. 43-9. 14. Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet, 2002. 360(9332): p. 505-15. 15. Bajetta, E., et al. Phase II study of vinorelbine in patients with pretreated advanced ovarian cancer: activity in platinum-resistant disease. J Clin Oncol, 1996. 14(9): p. 2546-51. 16. Kristensen, g., Chemotherapy versus hormonal treatment in patients with platinum and taxane resistant ovarian cancer: A NSGO study journal of clinical oncology, 2008. 26(suplement): p. abst5508.
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17. Dimopoulos, M.A., et al. Treatment of ovarian germ cell tumors with a 3-day bleomycin, etoposide, and cisplatin regimen: a prospective multicenter study. Gynecol Oncol, 2004. 95(3): p. 695-700. 18. Armstrong Dk, et. al. Intraperitoneal Cisplatin and Paclitaxel in Ovarian Cancer. New Engl Med 2006;354:34-43. 19. Kaye SS, et. al. Is cisplatin-taxol (PT) the standard treatment in advanced ovarian cancer. Eur J Cancer 1997:31-2167-70. 20. ChOllet P, et. al. Single agent activity of oxaliplatin in heavily pretreated advanced epithelial ovarian cancer Ann Oncol 1996; 7: 1065-70. 21. Motzer RJ, Sheinfeld J, Mazumdar M, et al. Paclitaxel, ifosfamide, and cisplatin second-line therapy for patients with relapsed testicular germ cell cancer. J Clin Oncol. 2000;18:2413-2418. 22. McCaffrey JA, Mazumdar M, Bajorin DF, et al. Ifosfamideand cisplatin-containing chemotherapy as first-line salvage therapy in germ cell tumors: Response and survival. J Clin Oncol . 1997; 15:2559-2563.
127
Doena Trofoblstica Gestacional

EP/EMA Etoposide: 150 mg/m2 IV D1 2 Cisplatina*: 75 mg/m IV D1 Etoposide:100 mg/m2 IV D8 2 Methotrexate: 300 mg/m IV(12hs) D8 Actinomicina: 0,5 mg IV D8 Leucovorin: 15 mg VO ou IV (4 doses; 12/1 2 hs) D9 (24hs aps metotrexato) a cada 14 dias 2 * Aplicar em 3 doses de 25/mg/m por 4 horas cada, diludo em 1000ml de soluo de Cloreto de Sdio a 0,9%. Ref. (1) Methotrexate Methotrexate: 1 mg/kg Leucovorin: 0,1 mg/kg Ref. (2)
IM D1, D3, D5 e D7 IM D2, D4, D6 e D8
a cada14 dias
Actinomicina Actinomicina: 1,25 mg/m2 IV Ref. (3)
D1
a cada 14 dias
EMA-CO Etoposide: 100 mg/m2 IV D1 e D2 2 Methotrexate: 300 mg/m IV (12hs)D1 Actinomicina: 0,5 mg IV D1 e D2 Leucovorin: 15 mg VO ou IV (4 doses; 12/1 2 hs) D2 (24 hs aps Methotrexate) Vincristina: 0,8 mg/m2 (mx. 2mg) IV D8 2 Ciclofosfamida: 600 mg/m IV D8 a cada 14 dias Ref. (4)
128
1. Newlands ES, et al. Etoposide and Cisplatin/Etoposide, Methotrexate, and Actinomycin D (EMA) Chemotherapy for Patients With High-Risk Gestational Trophoblastic Tumors Refractory to EMA/Cyclophosphamide and Vincristine Chemotherapy and Patients Presenting With Metastatic Placental Site Trophoblastic Tumors J Clin Oncol 200;18:854-9. 2. Berkowitz RS, et al. Ten years' experience with methotrexate and folinic acid as primary therapy for gestational trophoblastic disease. Gynecol Oncol 1986;23:111-8. 3. Chen LM, et al. Single-agent pulse dactinomycin has only modest activity for methotrexate-resistant gestational trophoblastic neoplasia. Gynecol Oncol 2004;94:204-7. 4. Bower M, et al. EMA/CO for high-risk gestational trophoblastic tumors: results from a cohort of 272 patients [published erratum appears in J Clin Oncol 1997 Sep;15(9):3168]. J Clinc Oncol 1997;15:2636-43.
129
Cncer de Vulva
Cisplatina + 5-Fluorouracil Cisplatina: 50 mg/m2 IV D1 5-Fluorouracil: 1000 mg/m2 IV D1 D4 a cada 21 dias Ref. (1) Paclitaxel Paclitaxel: 175 mg/m2 IV D1 D4 a cada 21 dias Ref. (2) 1. Moore DH, Thomas GM, Montana GS, Saxer A, Gallup DG, Olt G. Preoperative chemoradiation for advanced vulvar cancer: a phase II study of the Gynecologic Oncology Group. Int J Radiat Oncol Biol Phys 1998;42:79-85. 2. Witteveen P.O. Velden, I. J. Van Der Vergote, Oliveira C.F. de, et al. Phase II study on paclitaxel in patients with recurrent, metastatic or locally advanced vulvar cancer not amenable to surgery or radiotherapy: A study of the EORTC-GCG (European Organisation for Research and Treatment of Cancer-Gynaecological Cancer Group). Ann of Oncol. 2009; 20: 1511- 1516.
130
Cncer de Pulmo No Pequenas Clulas

Carboplatina + Paclitaxel Paclitaxel: 200mg/m2 IV Carboplatina: AUC 6 IV Ref. (1) Vinorelbina + Cisplatina Vinorelbina: 25mg/m2 IV 2 Cisplatina: 50mg/m IV ciclos Carboplatina + Paclitaxel Carboplatina: AUC 6 IV Paclitaxel: 200 a 225mg/m2IV D1 Ref. (3) OU Paclitaxel: 100mg/m2 Carboplatina: AUC 6 Ref. (4) IV IV D1 D1 SEMANAL a cada 28 dias D1 D1 a cada 21 dias X 4 ciclos
D1 semanal X 16 semanas D1 e D8 a cada 28 dias X 4 Ref. (2)
D1 a cada 21 dias
Carboplatina + Paclitaxel+ Bevacizumabe Paclitaxel: 200mg/m2 IV D1 Carboplatina: AUC 6 IV D1 Bevacizumabe: 15mg/kg IV D1 a cada 21 dias Ref. (3)
131
Cisplatina + Paclitaxel Cisplatina: 80mg/m2 Paclitaxel: 175mg/m2 Ref. (5)
IV IV
Docetaxel + Carboplatina Docetaxel: 75mg/m2 IV Carboplatina: AUC 6 IV Ref. (6) Docetaxel + Cisplatina Docetaxel: 75mg/m2 IV 2 Cisplatina: 75mg/m IV Ref. (6, 7) Docetaxel + Gencitabina Docetaxel: 100mg/m2 IV Gencitabina: 1100mg/m2 IV G-CSF: 300mcg SC Ref. (8) Cisplatina + Gencitabina Cisplatina: 100mg/m2 IV 2 Gencitabina: 1000mg/m IV 28 dias Carboplatina + Gencitabina Carboplatina: AUC 5 IV 2 Gencitabina: 1000mg/m IV 28 dias Ref. (10) Gencitabina + Vinorelbina Gencitabina: 1200mg/m2 IV Vinorelbina: 30mg/m2 IV Ref. (11)
D8 D1 e D8 D9 a D15
a cada 21 dias
D1 D1, D8 e D15 Ref. (9)
cada
D1 D1, D8 e D15
cada
D1 e D8 D1 e D8 a cada 21 dias
132
Vinorelbina + Carboplatina Vinorelbina: 25mg/m2 IV Carboplatina: AUC 6 IV Ref. (12) Pemetrexede + Cisplatina Pemetrexede: 500mg/m2 IV Cisplatina: 75mg/m2 IV Ref. (13) Pemetrexede + Carboplatina Pemetrexede: 500mg/m2 IV Carboplatina: AUC5 IV EP Etoposide: 120mg/m2 Cisplatina: 60mg/m2 Ref. (15) Paclitaxel Paclitaxel: 225mg/m2 Ref. (16) OU Paclitaxel: 80-100mg/m2 IV Ref. (17) Docetaxel Docetaxel: 75mg/m2 Ref. (18) OU Docetaxel: 35mg/m2 Ref. (19)
D1 e D8 D1 a cada 28 dias
D1 D1 a cada 21 dias Ref. (14)
IV IV
D1-D3 D1 a cada 21 dias
IV
D1 a cada 21 dias
D1-D8-D15 a cada 21 dias
IV
D1 a cada 21 dias
IV
D1, D8 e D15 a cada 28 dias
133
Pemetrexede Pemetrexede: 500mg/m2 IV Ref. (20) Gencitabina Gencitabina: 1000mg/m2 IV 28 dias Vinorelbina Vinorelbina: 25mg/m2 Ref. (22) Gefitinibe Gefitinibe: 250mg/m2 Ref. (23) Erlotinibe Erlotinibe: 150mg/dia
D1 a cada 21 dias
D1, D8, D15 Ref. (21)
cada
IV
D1
Semanal
VO
Contnuo
VO
Contnuo
Ref. (24)
Bevacizumabe+ Cisplatina+ Gencitabina Bevacizumabe: 7,5mg/kg IV D1 2 Cisplatina: 80mg/m IV D1 2 Gencitabina: 1200mg/m IV D1 e D8 a cada 21 dias Ref. (25) Cetuximabe+ Cisplatina + Vinorelbina Cetuximabe: 400mg/m2 IV D1 ATAQUE 2 Cetuximabe: 250mg/m IV Semanal Cisplatina: 80mg/m2 IV D1 Vinorelbina: 25mg/m2 IV D1 e D8 a cada 21 dias Ref. (26)
134
Vinblastina + Cisplatina Vinblastina: 4mg/m D1, D8, D15 e D28. Aps o D43, repetir o ciclo a cada 2 semanas at a ltima administrao de cisplatina. Cisplatina: 80mg/m IV D1 Repetir a cisplatina cada 21 dias por 4 ciclos (D1, D22, D43 e D64). Ref. (27) Etoposide + Cisplatina Etoposide: 100mg/m IV D1 ao D3 com cada administrao de cisplatina. Cisplatina: 80mg/m IV D1 a cada 28 dias no total de 4 ciclos Ref. (28) MIP Mitomicina: 6 mg/m2 Ifosfamida: 3000 mg/m2 Cisplatina: 50 mg/m2 Ref. (29) MIP(2) Mitomicina: 6 mg/m2 Ifosfamida: 1500 mg/m2 Cisplatina: 30 mg/m2 2 ciclos Ref. (30)
IV IV IV
D1 D1 D1 a cada 21 dias por 3 ciclos
IV IV IV
D1 D1 a D3 D1 a D3 a cada 21 dias por
Cisplatina + Irinotecano Cisplatina: 80 mg/m2 IV Irinotecano: 60 mg/m2 IV Ref. (31)
D1 D1, D8 e D15 a cada 28 dias
135
Carboplatina + Paclitaxel Carboplatina: AUC:6 IV 2 Paclitaxel: 90 mg/m IV Ref. (32)
D1 D1, D8 e D15 a cada 28 dias
1. Strauss, G.M., et al. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol, 2008. 26(31): p. 5043-51. 2. Winton, T., et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med, 2005. 352(25): p. 2589-97. 3. Sandler, A., et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med, 2006. 355(24): p. 2542-50. 4. Belani, C.P., et al. Randomized, phase III study of weekly paclitaxel in combination with carboplatin versus standard every-3-weeks administration of carboplatin and paclitaxel for patients with previously untreated advanced non-smallcell lung cancer. J Clin Oncol, 2008. 26(3): p. 468-73. 5. Giaccone, G., et al. Randomized study of paclitaxel-cisplatin versus cisplatin-teniposide in patients with advanced nonsmall-cell lung cancer. The European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol, 1998. 16(6): p. 2133-41. 6. Fossella, F., et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol, 2003. 21(16): p. 3016-24. 7. Belani, C.P., et al. Docetaxel and cisplatin in patients with advanced non small-cell lung cancer (NSCLC): a multicenter phase II trial. Clin Lung Cancer, 1999. 1(2): p. 144-50. 8. Georgoulias, V., et al. Platinum-based and non-platinum-
136
based chemotherapy in advanced non-small-cell lung cancer: a randomised multicentre trial. Lancet, 2001. 357(9267): p. 1478-84. 9. Abratt, R.P., et al. Weekly gemcitabine with monthly cisplatin: effective chemotherapy for advanced non-small-cell lung cancer. J Clin Oncol, 1997. 15(2): p. 744-9. 10. Langer, C.J., et al. Gemcitabine and carboplatin in combination: an update of phase I and phase II studies in nonsmall cell lung cancer. Semin Oncol, 1999. 26(1 Suppl 4): p. 12-8. 11. Frasci, G., et al. Gemcitabine plus vinorelbine versus vinorelbine alone in elderly patients with advanced nonsmall-cell lung cancer. J Clin Oncol, 2000. 18(13): p. 2529-36. 12. Cremonesi, M., et al. Vinorelbine and carboplatin in inoperable non-small cell lung cancer: a monoinstitutional phase II study. Oncology, 2003. 64(2): p. 97-101. 13. Scagliotti, G.V., et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage nonsmall-cell lung cancer. J Clin Oncol, 2008. 26(21): p. 3543-51. 14. Scagliotti, G.V., Pemetrexed plus carboplatin or oxaliplatin in advanced non-small cell lung cancer. Semin Oncol, 2005. 32(2 Suppl 2): p. S5-8. 15. Longeval, E. and J. Klastersky, Combination chemotherapy with cisplatin and etoposide in bronchogenic squamous cell carcinoma and adenocarcinoma. A study by the EORTC lung cancer working party (Belgium). Cancer, 1982. 50(12): p. 2751-6. 16. Lilenbaum, R.C., et al. Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the cancer and leukemia group B (study 9730). J Clin Oncol, 2005. 23(1): p. 190-6. 17. Tester, W.J., et al. Phase II study of patients with metastatic nonsmall cell carcinoma of the lung treated with paclitaxel by 3-hour infusion. Cancer, 1997. 79(4): p. 724-9. 18. Miller, V.A. and M.G. Kris, Docetaxel (Taxotere) as a single agent and in combination chemotherapy for the treatment
137
of patients with advanced non-small cell lung cancer. Semin Oncol, 2000. 27(2 Suppl 3): p. 3-10. 19. Hainsworth, J.D., et al. Weekly docetaxel in the treatment of elderly patients with advanced nonsmall cell lung carcinoma. A Minnie Pearl Cancer Research Network Phase II Trial. Cancer, 2000. 89(2): p. 328-33. 20. Hanna, N., et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol, 2004. 22(9): p. 1589-97. 21. Manegold, C., et al. Single-agent gemcitabine versus cisplatin-etoposide: early results of a randomised phase II study in locally advanced or metastatic non-small-cell lung cancer. Ann Oncol, 1997. 8(6): p. 525-9. 22. Furuse, K., et al. Randomized study of vinorelbine (VRB) versus vindesine (VDS) in previously untreated stage IIIB or IV non-small-cell lung cancer (NSCLC). The Japan Vinorelbine Lung Cancer Cooperative Study Group. Ann Oncol, 1996. 7(8): p. 815-20. 23. Herbst, R.S., Dose-comparative monotherapy trials of ZD1839 in previously treated non-small cell lung cancer patients. Semin Oncol, 2003. 30(1 Suppl 1): p. 30-8. 24. Rosell, R., et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med, 2009. 361(10): p. 958-67. 25. Reck, M., et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol, 2009. 27(8): p. 1227-34. 26. Pirker, R., et al. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an openlabel randomised phase III trial. Lancet, 2009. 373(9674): p. 1525-31. 27. Arriagada R, Bergman B, Dunant A, et al. The International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-
138
based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. N Engl J Med 2004;350:351-60. 28. Arriagada R, Bergman B, Dunant A, et al. The International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatinbased adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. N Engl J Med 2004;350:351-60. 29. Rosell R,et al. A Randomized Trial Comparing Preoperative Chemotherapy Plus Surgery With Surgery Alone In Patients With Non-Small-Cell Lung Cancer. N Engl Med 1994:330:153-8. 30. Depierre A., et al. Preoperative Chemotherapy Followed by Surgery Compared With Primary Surgery in Resectable Stage I (Except T1N0), II, and IIIa NonSmall-Cell Lung Cancer. J Clin Oncol 2002;20:247-251. 31. DeVore RF, et al. Phase II Study of Irinotecan Plus Cisplatin in Patients With Advanced NonSmall-Cell Lung Cancer. J CIin Oncoll 1999:17:2710-20. 32. Quoix E. A., Oster J., Westeel V., et al. Weekly paclitaxel combined with monthly carboplatin versus single-agent therapy in patients age 70 to 89: IFCT-0501 randomized phase III study in advanced non-small cell lung cancer (NSCLC). J Clin Oncol 28:18s, 2010 (suppl; abstr 2).
139
Cncer de Pulmo de Pequenas Clulas

EP + Radioterapia Etoposide: 100mg/m IV D1 ao D3 Cisplatina: 80mg/m IV D1 a cada 28 dias no total de 4 ciclos, concomitante a radioterapia Ref. (1) CAV seguido de EP + Radioterapia Ciclofosfamida: 1000 mg/m IV D1 Doxorrubicina: 50 mg/m IV D1 Vincristina: 1mg/m IV D1 (mximo 2mg) 3 semanas aps CAV, administrar EP. Alternar CAV e EP a cada 3 semanas. Etoposide: 100mg/m IV D22 ao D24 Cisplatina: 25mg/m IV D22 Iniciar radioterapia torcica 20 a 30 Gy concomitante ao EP Ref. (2) EP Etoposide: 120 mg/m IV D1 ao D3 ou etoposide 120mg/m IV D1 e 240mg/m VO D2 e D3 Cisplatina: 80 mg/m IV D1 a cada 21 dias Ref. (3) EC Etoposide: 100 mg/m IV D1 ao D3 Carboplatina: AUC de 6 IV D1 a cada 28 dias Ref. (4)
140
Irinotecano + Cisplatina Irinotecano: 60 mg/m IV D1, D8 e D15 Cisplatina: 60 mg/m IV D1 a cada 28 dias Ref. (5) Carboplatina + Irinotecano Carboplatina: AUC de 4 IV D1 Irinotecano: 175mg/m IV D1 a cada 21 dias Ref. (6) Carboplatina + Paclitaxel Paclitaxel: 200mg/m IV D1 Carboplatina: AUC 6 IV D1 a cada 21 dias Ref. (7) Carboplatina + Paclitaxel + Etoposide Carboplatina: AUC 6 IV D1 Paclitaxel: 200 mg/m IV durante 1 hora D1 Etoposide: 50 mg alternando com 100 mg VO D1 ao D10 a cada 21 dias Ref. (8) CAE Ciclofosfamida: 1000mg/m IV D1 Doxorrubicina: 50mg/m IV D1 Etoposide: 120mg/m IV D1 e 240mg/m VO D2 e D3 a cada 21 dias Ref. (9) Paclitaxel Paclitaxel: 80-100 mg/m IV semanalmente por 3 semanas a cada 28 dias Ref. (10)
141
Topotecano Topotecano: 4mg/m IV semanalmente em 30 minutos OU Topotecano: 2,3mg/m VO D1 ao D5 a cada 21 dias Ref. (11)
1. Takada M. et al. Phase III Study of Concurrent Versus Sequential Thoracic Radiotherapy in Combination With Cisplatin and Etoposide for Limited-Stage Small-Cell Lung Cancer: Results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol 20:3054, 2002. 2. Murray N. et al. Abbreviated treatment for elderly, infirm or noncompliant patients with limited-stage small-cell lung cancer. J Clin Oncol 16: 3323, 1998. 3. Ihde DC, et al. Prospective randomized comparison of highdose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive stage small cell lung cancer. J Clin Oncol 1994;12:2022-2034. Baka S. et al. Phase III randomised trial of doxorubicin-based chemotherapy compared with platinum-based chemotherapy in small-cell lung cncer. Br J Cancer99: 442, 2008 4. Viren M, et al. Carboplatin and etoposide in extensive small cell lung cancer. Acta Oncol 1994;33:921-924. 5. Noda K, et al. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small cell lung cancer. N Engl J Med 2002;346:85-91. 6. Hermes A. et al. Irinotecan Plus Carboplatin Versus Oral Etoposide Plus Carboplatin in Extensive Small-Cell Lung Cancer: A Randomized Phase III Trial. J Clin Oncol 26: 4261, 2008. 7. Baka S. et al. Randomized phase III study of carboplatin and paclitaxel versus vincristine, doxorubicin and cyclophosphamide
142
chemotherapy in intermediate and poor prognosis small cell lung cancer: Preliminary results. J Clin Oncol 24: abstr 7059, 2006. 8. Hainsworth JD, et al. Paclitaxel, carboplatin and extendedschedule etoposide in the treatment of small cell lung cancer comparison of sequential phase II trials using different dose-intensities. J Clin Oncol 1997;15:3464-3470. 9. Baka S. et al. Phase III randomised trial of doxorubicin-based chemotherapy compared with platinum-based chemotherapy in small-cell lung cncer. Br J Cancer99: 442, 2008. 10. Hainsworth JD, et al. The current role and future prospects of paclitaxelin in the treatment of small cell lung cancer. Semin Oncol 1999;26 (Suppl 2):60-66. 11. Shipley D. L. et al. Topotecan: Weekly intravenous (IV) schedule similar to standard 5-day IV schedule as secondline therapy for relapsed small cell lung cancer (SCLC)A Minnie Pearl Cancer Research Network phase II trial . J Clin Oncol 24: abstr 7083, 2006. Mary E.R.et al. Phase III Trial Comparing Supportive Care Alone With Supportive Care With Oral Topotecan in Patients With Relapsed Small-Cell Lung Cncer. J Clin Oncol 24: 5441, 2006.
143
Mesotelioma
Cisplatina + Doxorrubicina Doxorrubicina: 60mg/m2 Cisplatina: 60mg/m2 Ref. (1) CAP Ciclofosfamida: 500mg/m2 Doxorrubicina: 50mg/m2 Cisplatina: 80mg/m2 Ref. (2) Gencitabina + Cisplatina Gencitabina: 1000mg/m2 IV Cisplatina: 100mg/m2 IV Ref. (3) Gencitabina+ Carboplatina Gencitabina: 1000mg/m2 IV Carboplatina: AUC 5 IV Ref. (4) Pemetrexede + Cisplatina Pemetrexede: 500mg/m2 IV Cisplatina: 75mg/m2 IV Ref. (5) IV IV D1 D1 a cada 21 dias
IV IV IV
D1, D8, D15 D1 a cada 28 dias
D1, D8, D15 D1 a cada 28 dias
D8 D1, D8
a cada 21 dias
Pemetrexede Pemetrexede: 500mg/m2 IV em 10 min D1 a cada 21 dias Ref. (6)
144
Vinorelbina Vinorelbina: 30mg/m2 IV D1 semanalmente durante 6 ou 12 semanas (com intervalo de 2 semanas entre a 6a e 7a dose). Ref. (7) Pemetrexede + Carboplatina Pemetrexede: 500mg/m2 IV Carboplatina: AUC de 5 IV a cada 21 dias Ref. (8) Cisplatina e Raltitrexede Cisplatina : 80 mg/m2 IV Raltitrexede: 3 mg/m2 IV Ref. (9) Raltitrexede Raltitrexede: 3 mg/m2 Ref. (10)
D1 D1
D1 D1
a cada 21 dias
IV
D1
a cada 21 dias
1. Ardizzoni, A., et al. Activity of doxorubicin and cisplatin combination chemotherapy in patients with diffuse malignant pleural mesothelioma. An Italian Lung Cancer Task Force (FONICAP) Phase II study. Cancer, 1991. 67(12): p. 2984-7. 2. Shin, D.M., et al. Prospective study of combination chemotherapy with cyclophosphamide, doxorubicin, and cisplatin for unresectable or metastatic malignant pleural mesothelioma. Cancer, 1995. 76(11): p. 2230-6. 3. Nowak, A.K., et al. A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma. Br J Cancer, 2002. 87(5): p. 491-6. 4. Favaretto, A.G., et al. Gemcitabine combined with carboplatin in patients with malignant pleural mesothelioma: a multicentric phase II study. Cancer, 2003. 97(11): p. 2791-7.
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5. Vogelzang, N.J., et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol, 2003. 21(14): p. 2636-44. 6. Taylor, P et al. Single-Agent Pemetrexed for Chemonaive and Pretreated Patients with Malignant Pleural Mesothelioma: Results of an International Expanded Access Program. Journal of Thoracic Oncology, 2008;3:764-771. 7. Stebbing J, et al. The efficacy and safety of weekly vinorelbine in relapsed malignant pleural mesothelioma. Lung Cancer 2009; 63:94-7. 8. Ceresoli GL, et al. Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. J Clin Oncol 2006; 24:1443-1448. 9. van Meerbeeck JP, et al. Randomized Phase III Study of Cisplatin With or Without Raltitrexed in Patients With Malignant Pleural Mesothelioma: An Intergroup Study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada. J Clin Oncol 2005;23:6881-9. 10. Baas P, et al. The activity of raltitrexed (Tomudex) in malignant pleural mesothelioma: an EORTC phase II study (08992). Eur J Cancer 2003;39:353-7.
146
Timoma
CAP Ciclofosfamida: 500 mg/m IV D1 Doxorubicina: 50 mg/m IV D1 Cisplatina: 50 mg/m IV D1 a cada 21 dias Ref. (1) Cisplatina + Etoposide Cisplatina: 60 mg/m IV D1 Etoposide: 120 mg/m IV D1 ao D3 a cada 21 dias Ref. (2) CAPP Ciclofosfamida: 500 mg/m IV D1 Doxorrubicina: 20 mg/m/dia IV D1 ao D3 (total de 60 mg/m) Cisplatina: 30 mg/m IV D1 ao D3 Prednisona: 100 mg VO/dia D1 ao D5 a cada 21 dias Ref. (3) PEE Cisplatina: 75 mg/m IV D1 Epirrubicina: 100 mg/m IV D1 Etoposide: 120 mg/m IV D1, D3 e D5 a cada 21 dias Ref. (4)
147
ADOC Cisplatina: 50 mg/m IV D1 Doxorubicina: 40 mg/m IV D1 Vincristina: 0,6 mg/m IV D3 Ciclofosfamida: 700 mg/m IV D4 a cada 28 dias Ref. (5)
1. Loehrer PJ, et al. Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. J Clin Oncol 1994;12:11641168. 2. Giaccone G, et al. Cisplatin and etoposide combination chemotherapy for locally advanced or metastatic thymoma. A phse II study of the European Organization for Research and Treatment of cancer Lung Cancer Cooperative Group. J Clin Oncol 1996;14:814-820. 3. Kim ES, et al. Phase II study of a multidisciplinary approach with induction chemotherapy, followed by surgical resection, radiation therapy, and consolidation chemotherapy for unresectable malignant thymomas: final report. Lung Cncer 44:369-379,2004. 4. Venuta F, et al. Multimodality Treatment of Thymoma: A Prospective Study. Ann Thorac Surg 1997;64:1585-1591. 5. Fornastero A, et al. Chemotherapy for invasive thymoma. Cancer 1991;68:30-33.
148
Melanoma Maligno
Alfainterferon 2b em altas doses Induo: 20 MUI/m/dia IV durante 20 min, 5 vezes por semana, durante 4 semanas Consolidao/Manuteno: 10 MUI/m/dia SC, 3 vezes por semana durante 48 semanas. Ref. (1) Dacarbazina (DTIC)* Dacarbazina: 250 mg/m/dia IV durante 30-60 minutos D1 ao D5 a cada 21 ou 28 dias OU Dacarbazina: 1000 mg/m/dia IV durante 30 minutos D1 a cada 21 dias Ref. (2) Alfainterferon 2b Alfainterferon 2b: 20 MUI/m/dia IM, 3 vezes por semana durante 12 semanas. Ref. (3) Interleucina-2 (IL-2) em altas doses Interleucina-2: 720.000 UI/kg IV durante 15 minutos a cada 8h mximo 12 a 15 doses por ciclo (do D1 ao D4 ou do D1 ao D5). A primeira dose do segundo curso de IL-2 deve ser administrada 14 dias aps a primeira dose do primeiro curso. a cada 6 a 12 semanas Ref. (4)
149
Temozolomida Temozolomida: 200 mg/m/dia VO D1-5. a cada 28 dias
Ref. (5)
Fotemustina Induo: 100mg/m2 IV durante 60 min D1, D8 e D15, com intervalo de 05 semanas. Manuteno: 100mg/m2 IV durante 60 min D1 a cada 03 semanas. Ref. (6) Dacarbazina (DTIC) + Carmustina (BCNU) + Cisplatina Dacarbazina: 220 mg/m/dia IV em 30-60 min D1 ao D3 a cada 21 dias Cisplatina: 25 mg/m/dia IV em 30-45 min D1 ao D3 a cada 21 dias Carmustina: 150 mg/m IV durante 2 a 3 horas D1 a cada 42 dias. Ref. (7) Paclitaxel + Carboplatina Paclitaxel: 100 mg/m2 IV durante 1 hora Carboplatina: AUC 2 IV em 30 min D1, D8 e D15 a cada 28 dias. OU Paclitaxel: 175-200 mg/m2 IV durante 3 horas Carboplatina: AUC 5 IV em 60min D1 a cada 21 dias. Ref. (8)
Bioquimioterapia
Cisplatina + Vinblastina + Dacarbazina + IL-2 + IFN 2b Cisplatina: 20mg/m2/dia IV em 30 min D1 ao D4 Vinblastina: 1,2mg/m2/dia IV pulso D1 ao D4 Dacarbazina: 800 mg/m2/dia IV em 1 hora D1 (administrar 1 hora aps Vinblastina)
150
IL-2: 9 MUI/m2 IV em 24h infuso contnua D1-4 (total de 96h) Alfainterferon 2b: 5 MUI/m2 SC D1 ao D5, D8, D10 e D12 Filgrastima: 5mcg/Kg/d SC D7 ao D16 a cada 21 dias, com o mximo de 4 ciclos. Ref. (9) Paclitaxel Paclitaxel: 90 mg/m2 IV(80min) D1, D5 e D9 Ref. (10) CVD Cisplatina: 20mg/m2/dia IV Vinblastina: 1,6mg/m2/dia IV Dacarbazina: 800 mg/m2 IV Ref. (11)
a cada 21 dias
D2 a D5 D1 a D5 D1 a cada 21 dias
Regime Dartmouth* Carmustina: 150 mg/m2 IV D1 Cisplatina: 25 mg/m2 IV D1 a D3 2 Dacarbazina: 220 mg/m IV D1 a D3 a cada 21 dias *Alm dos quimioterpicos, o regime inclui tambm tamoxifeno, 10 mg, 2 vezes ao dia, com incio 1 semana antes da quimioterapia e tomado de forma contnua. Ref. (12) 1. Kirkwood JM, et al. Interferon alfa-2b adjuvant therapy of high risk resected cutaneous melanoma: the Eastern Cooperative Oncology Trial EST 1684. J Clin Oncol 1996;14:7-17. Kirkwood JM, et al. High-dose Interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of Intergroup Trial E1694/S9512/ C509801. J Clin Oncol 2001;19:2370-80. Kirkwood JM, et al. A pooled Analysis of Eastern Cooperative Oncology Group and Intergroup Trials of Adjuvant High Dose Interferon for Melanoma. Clin Cancer Res 2004; 10:1670-1677.
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2. Middleton MR, et al. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol 2000; 18: 15866. Avril, MF et al. Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study. J Clin Oncol 2004; 22:1118-25. Chapman PB, et al. Phase III multicentric randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma. J Clin Oncol 1999; 17:2745-51. Eigentler, TK et al. Palliative therapy of disseminated malignant melanoma: a systematic review of 41 randomised clinical trials. Lancet Oncol 2003;4:748-59. 3. Kirkwood JM, et al. Advances in the diagnosis and treatment of malignant melanoma. Semin Oncol 1997;24 (suppl 4): 1-48. 4. Smith, FO et al. Treatment of metastatic melanoma using Interleukin-2 alone or in conjunction with vaccines. Clin Cancer Res 2008;14:5610-18. Atkins, MB et al. High-Dose recombinant Interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 1999; 17: 2105-16. Schwartzentruber, DJ. Guidelines for the safe administration of high-dose interleukin-2. J Immunother 2001; 24:287-93. 5. Middleton MR, et al. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol 2000;18:158-166. 6. Avril, MF et al. Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study. J Clin Oncol 2004; 22:1118-1125. 7. Chapman PB, et al. Phase III multicentric randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma. J Clin Oncol 1999; 17:2745-51. Creagen ET, et al. Phase III clinical trial of the combination of
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cisplatin, dacarbazine, and carmustine with or without tamoxifen in patients with advanced malignant melanoma. J Clin Oncol 1999;17:1884-1890. 8. Rao, RD et al. Combination of paclitaxel and carboplatin as second-Line therapy for patients with metastatic melanoma. Cancer 2006;106:375-82. 9. Atkins,MB et al. Phase III trial comparing concurrent biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin-2, and interferon alfa-2b with cisplatin, vinblastine, and dacarbazine alone in patients with metastatic malignant melanoma (E3695): a trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol 2008; 26:5748-5754. 10. Bedikian AY, et al. Phase II evaluation of paclitaxel by short intravenous infusion in metastatic melanoma Melanoma Res 2004;14:63-6. 11. Legha SS, et al. A prospective evaluation of a triple-drug regimen containing cisplatin, vinblastine, and dacarbazine (CVD) for metastatic melanomaCancer 1989;64:2024-9. 12. Chapman PS, et al. Phase III Multicenter Randomized Trial of the Dartmouth Regimen Versus Dacarbazine in Patients With Metastatic Melanoma. J Clin Oncol 1999; 17:2745-51.
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Linfoma de Hodgkin
BEACOPP escalonado Bleomicina: 10 mg/m IV D8 Etoposide: 200 mg/m IV D1 ao D3 Doxorrubicina: 35 mg/m IV D1 Ciclofosfamida: 1250 mg/m IV D1 Vincristina: 1,4 mg/m IV D8 (dose mxima 2 mg) Procarbazina: 100 mg/m VO D1 ao D7 Prednisona: 40 mg/m VO D1 ao D14 Filgrastima: 5 g/kg/dia SC, iniciando no D8 at a recuperao dos neutrfilos. a cada 21 dias Ref. (01) DHAP Dexametasona: 40mg VO D1 ao D4 Cisplatina: 100mg/m IV em infuso contnua por 24h D1 Citarabina: 2000 mg/m IV em 2 horas 12/12h D2 Filgrastima: 300mcg SC D4 ao D13 Devem ser realizados 2-4 ciclos e no caso de resposta, coleta de clulas progenitoras e posterior TMO Profilaxia de conjuntivite por citarabina com colrio de dexametasona. Ref. (02) ICE Ifosfamida: 5mg/m IV D2 Etoposide: 100mg/m IV D1 ao D3 Carboplatina: AUC 5 IV D2 A Ifosfamida deve ser associada a Mesna na dose de 5000 mg/m. a cada 14 dias Filgrastima: 5 g/kg D5 ao D12. Ref. (03)
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Gencitabina Gencitabina: 1250 mg/m IV D1, D8 e D15 a cada 28 dias Ref. (04) Gencitabina + Vinorelbina + Doxorrubicina Lipossomal Peguilada Vinorelbina: 20mg/m IV D1 e D8 em 10 min, sendo a 1 droga Gencitabina: 1000 mg/m IV D1 e D8 em 30 min, sendo a 2 droga Doxorrubicina Lipossomal Peguilada: 15mg/m IV D1 e D8 em 30-60 min a cada 21 dias Ref. (05) ABVD Doxorrubicina: 25mg/m Bleomicina: 10UI/m Vinblastina: 6mg/m Dacarzabina: 375mg/m a cada 28 dias Ref. (06)
IV IV IV IV
D1 e 15 D1 e 15 D1 e 15 D1 e 15
MOPP Mustarda Nitrogenada: 6mg/m Vincristina: 1,4mg/m Procarbazina: 100mg/m Prednisona: 40mg/m a cada 28 dias Ref. (07)
IV IV VO VO
D1 e 8 D1 e 8 D1 a 14 D1 a 14
MOPP/ABVD HBRIDO Mustarda Nitrogenada: 6mg/m IV D1 e 8 Vincristina: 1,4mg/m IV D1 ( Dose mxima de 2mg) Procarbazina: 100mg/m VO D1 a 14 Prednisona: 40mg/m IV D1 a 14
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Doxorrubicina: 35mg/m Bleomicina: 10UI/m Hidrocortisona: 100mg Vinblastina: 6mg/m a cada 28 dias Ref. (08)
IV D8 IV D8 IV dada antes da Bleomicina IV D8
EVA Etoposide: 200 mg/m2 IV D1-5 Vincristina: 2mg/m2 IV D1 Doxorrubicina: 50 mg/m2 IV D2 a cada 28 dias Ref. (09) EVAP Etoposide: 120 mg/m2 IV D1, 8 e 15 Vinblastina: 4 mg/m2 IV D1, 8 e 15 Citarabina: 30 mg/m2 IV D1, 8 e 15 Cisplatina: 40 mg/m2 IV D1, 8 e 15 a cada 28 dias Ref. (10) Mini- BEAM BCNU: 60 mg/m2 IV D1 Etoposide: 75 mg/m2 IV D2-5 Ara-C: 100 mg/m2 IV a cada 12 horas D2-5 Melfalano: 30 mg/m2 IV D6 a cada 4 a 6 semanas Ref. (11) BEACOPP Bleomicina: 10 mg/m2 IV D 8 Etoposide: 100 mg/m2 IV D1-3 Doxorrubicina: 25 mg/m2 IV D1 Ciclofosfamida: 650 mg/m2 IV D1
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Vincristina: 1.4 mg/m2 IV D (mximo 2 mg) Procarbazina: 100 mg/m2 VO D1-7 Prednisona: 40 mg/m2 VO D1-14 a cada 21 dias Ref. (12) Stanford V Doxorrubicina: 25 mg/m2 IV semanas 1, 3, 5, 7, 9 e 11 Vinblastina: 6 mg/m2 IV semanas 1, 3, 5, 7, 9 e 11 (dose reduzida para 4 mg/m2 nas semanas 9 e 11 em paciente 50 anos). Mustarda Nitrogenada: 6 mg/m2 IV nas semanas 1, 5 e 9. Etoposide: 60mg/m2 IV por 2 dias nas semanas 3, 7 e 11. Vincristina: 1,4 mg/m2 IV nas semanas 2, 4, 6, 8,10 e 12. (A dose reduzida para 1 mg/m2 nas semanas 10 e 12 em paciente 50 anos). Bleomicina: 5 UI/m2 IV nas semanas 2,4,6,8,10 e 12. Prednisona: 40 mg/ m2 VO em dias alternados por 10 semanas com desmame a cada 2 dias da semana 10 a 12. Ref .(13)
1. Diehl V; Franklin J; Pfreundschuh M; Lathan B; Paulus U; Hasenclever D; Tesch H; Herrmann R; Dorken B; MullerHermelink HK; Duhmke E; Loeffler M. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease.N Engl J Med 2003 Jun 12;348(24):2386-95. 2. Josting A. et al. Time-intensified dexamethasone/cisplatin/ cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkins disease. Ann Oncol 13:1628, 2002.
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3. Abali H. et al. Comparison of ICE (Ifosfamide-CarboplatinEtoposide) Versus DHAP (Cytosine Arabinoside-CisplatinDexamethasone) as Salvage Chemotherapy in Patients with Relapsed or Refractory Lymphoma.Cancer investigation 2008, Vol. 26, No. 4, Pages 401-406. 4. Santoro A, et al. Gemcitabine in the treatment of refractory Hodgkins disease: results of a multicenter phase II study. J Clin Oncol 2000;18;2645-2619. 5. Barlet N. L. et al. Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkins lymphoma: CALGB 59804. Annals of Oncology 18: 10711079, 2007. 6. Bonadonna G. et al. Combination Chemotherapy of Hodgkins disease With Adriamycin, bleomycin, Vinblastine, and Imidazole Carboxamide Versus Mopp. Cancer 1975; 36: 252259. 7. De Vita VT, Jr et al. Combination Chemotherapy in Tratamento of Advanced Hodgkins desease. Ann Intern Med 1970; 73; 881-895. 8. Klimo P. et al. Mopp/ABV hybrid program: Combination Chemotherapy baseol on Early introduction of seven effective drogs for advanced hodgkins disease. J Clin Oncol 1985; 3: 1174-1182. 9. Radford J, et al. Results of a randomized trial comparing MVPP chemotherapy with a hybrid regimen, CHLVPP/EVA, in the initiai treatment of Hodginkin's disease J. Clin Oncol 1995;13:2379-2385. 10. Longo Dl, The use of chemotherapy in the treatment of Hodgkin's disease. Semin Oncol 1990;17:716-735. 11. Colwill R, et al. Mini-Beam as salvage therapy for relapsed or refractory Hodgkin's disease before intensive therapy and autologous bon marrow transplantation. J Clin Oncol 1995;13:396-402. 12. Diehl V. et al. BEACOPP, a new dose-escalated and accelerated regimen is at least as effective as COPP/ABVD in
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patients with advanced-stage hodgkin's lymphoma. J Clin Oncol 1998:16:3810-3821. 13. Hoskin PJ, Lowry L, Horwich A, Jack A, et al. Randomized comparison of the Stanford V Regimen and ABVD in the treatment of advanced Hodgkin's Lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244. J Clin Oncol. 2009; 27:53905396.
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Linfoma No-Hodgkin
Rituximabe (LNH Folicular) Rituximabe: 375mg/m2 semanalmente por 4 semanas. Ref. (01) R CVP (linfomas CD20 positivo) Ciclofosfamida: 750 mg/m IV D1 Vincristina: 1,4 mg/m IV D1 (dose mxima 2 mg) Prednisona: 40 mg/m VO D1 ao D5 Rituximabe: 375mg/m IV D1 a cada 21 dias no total de 8 ciclos Ref. (02) R CHOP Rituximabe: 375mg/m2 D1 Ciclofosfamida: 750 mg/m IV D1 Doxorrubicina: 50 mg/m IV D1 Vincristina: 1,4 mg/m IV D1 (dose mxima 2 mg) Prednisona: 100 mg/m VO D1 ao D5 a cada 21 dias. Ref. (03) FND Fludarabina: 25 mg/m IV D1 ao D3 Mitoxantrona: 10 mg/m IV D1 Dexametasona: 20 mg VO D1 ao D5 a cada 21 dias Cuidados de Suporte Sulfametoxazol 800mg + Trimetoprima 160mg VO 1x/dia 3 dias por semana, at 3 meses aps trmino do tratamento Ref. (04)
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R-FND Rituximabe: 375mg/m IV D0 Fludarabina: 25 mg/m IV D1 ao D3 Mitoxantrona: 10 mg/m IV D1 Dexametasona: 20 mg VO D1 ao D5 a cada 21 dias Ref. (05) FC Fludarabina: 20 mg/m IV D1 ao D5 Ciclofosfamida: 1000 mg/m IV D1 a cada 21-28 dias Ref. (06) Fludarabina Fludarabina: 25 mg/m IV D1 ao D5 a cada 28 dias Ref. (07) CVP Ciclofosfamida: 400 mg/m2 VO D1 -5 (ou 800 mg/m2 IV D1) Vincristina: 1.4 mg/m2 IV D1 (mximo 2 mg) Prednisona: 100 mg/m2 VO D1-5 a cada 21 dias Ref. (08) CHOP Ciclofosfamida: 750 mg/m2 IV D1 Doxorrubicina: 50 mg/m2 IV D1 Vincristina: 1.4 mg/m2 IV D1 (mximo 2 mg) Prednisona: 100 mg/m2 VO D1-5 a cada 21 dias Ref. (09)
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CNOP Ciclofosfamida: 750 mg/m2 IV D1 Mitoxantrona: 10 mg/m2 IV D1 Vincristina: 1.4 mg/m2 IV D1 (mximo 2 mg) Prednisona: 50 mg/m2 VO D1-5 a cada 21 dias Ref. (10) CHOP + Rituximabe (Nebraska regimen) Ciclofosfamida: 750 mg/m2 IV D3 Doxorrubicina: 5O mg/m2 IV D3 Vincristina: 1.4 mg/m2 IV D3 (mximo de 2 mg) Prednisona: 100 mg VO D3-7 Rituximabe: 375 mg/m2 IV no D1 a cada 21 dias Ref. (11) CNOP Ciclofosfamida: 750 mg/m2 D1 Mitoxantrona: 10 mg/m2 IV D1 Vincristina: 1.4 mg/m2 IV D1 (mximo de 2 mg) Prednisona: 100 mg VO D1-5 a cada 21 dias Ref. (12) EPOCH Etoposide: 50 mg/m2/dia IV em infuso contnua D1-4 Prednisona: 60 mg/m2 VO D1-5 Vincristina: 0.4 mg/m2/dia IV em infuso contnua D1-4 Ciclofosfamida: 750 mg/m2 IV D5, iniciar aps infuso contnua Doxorrubicina: 10 mg/m2/dia IV em infuso contnua D1-4 a cada 21 dias Ref. (13)
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EPOCH + Rituximabe Etoposide: 50 mg/m2/dia IV em infuso contnua D1-4 Prednisona: 60 mg/m2 VO BID D1-5 Vincristina: 0.4 mg/m2/dia em infuso contnua D1-4 Ciclofosfamida: 750 mg/m2 IV D5, iniciar aps infuso contnua Doxorrubicina: 10 mg/m2/dia IV em infuso contnua D1-4 Rituximabe: 375 mg/m2 IV no dia 1 a cada 21 dias Ref. (14) MACOP-B Methotrexate: 400mg/m2 IV nas semanas 2,6 e 10 Leucovorin: 15mg/m2 VO a cada 6 horas por 6 doses, iniciando 24 horas aps o methotrexate Doxorrubicina: 50 mg/m2 IV nas semanas 1, 3, 5, 7, 9 e 11 Ciclofosfamida: 350 mg/m2 IV nas semanas 1, 3, 5, 7, 9 e 11 Vincristina: 1.4 mg/m2 IV nas semanas 2, 4, 6, 8, 10 e 12 Prednisona: 75mg/dia VO por 12 semanas com retirada nas 2 ltimas semanas Bleomicina: 10 U/m2 IV nas semanas 4, 8 e12 Bactrim F: 1 comp. VO BID Cetoconazol: 200 mg/dia VO Administrar um ciclo. Ref. (15) m-BACOD Methotrexate: 200 mg/m2 IV D8 e 15 Leucovorin: 10 mg/m2 VO a cada 6 horas por 8 doses, iniciando 24 aps o methotrexate Bleomicina: 4 U/m2 IV D1 Doxorubicina: 45 mg/m2 IV D1 Ciclofosfamida: 600 mg/m2 IV D1 Vincristina: 1 mg/m2 IV D1 (mximo de 2 mg) Dexametasona: 6 mg/m2 VO D1-5 a cada 21 dias Ref. (16)
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ProMACE/CytaBoM Prednisona: 60mg/m2 VO D1-14 Doxorrubicina: 25 mg/m2 IV D1 Ciclofosfamida: 650 mg/m2 IV D1 Etoposide: 120mg/m2 IV D1 Citarabina: 300mg/m2 IV D8 Bleomicina: 5 U/m2 IV D8 Vincristina: 1.4 mg/m2 IV D8 Methotrexate: 120 mg/m2 IV D8 Leucovorin resgate com: 25mg/m2 VO cada 6 horas por 6 doses, iniciando 24 horas aps o methotrexate Bactrim F: 1 comp. VO BID D1-21 a cada 21 dias Ref. (17) ESHAP (Regime de salvamento) Etoposide: 40 mg/m2 IV D1-4 Metilprednisolona: 500 mg IV D1-4 Cisplatina: 25 mg/m2/dia IV infuso contnua D1-4 Citarabina: 2,000 mg/m2 IV D5 depois de completar a cisplatina e etoposide a cada 21 dias Ref. (18) DHAP (Regime de salvamento) Cisplatina: 100 mg/m2 IV infuso contnua de 24 horas D1 Citarabina: 2,000 mg/m2 IV em infuso de 3 horas a cada 12 horas por 2 doses D2 aps trmino de infuso de cisplatina Dexametasona: 40 mg VO ou IV D1-4 a cada 3-4 semanas Ref. (19)
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ICE (Regime de salvamento) Ifosfamida: 5,000 mg/m2 IV infuso contnua de 24 horas D2 Etoposide: 100 mg/m2 IV D1-3 Carboplatina: AUC 5 IV D2 Mesna: 5,000 mg/m2 IV em combinao com a dose de Ifosfamida a cada 14 dias G-CSF administrado na dose de 5 g/kg D5-12. Ref. (20)
MINE (Regime de salvamento) Mesna: 1,330 mg/m2 IV administrar ao mesmo tempo de Ifosfamida D1 a 3, seguido por 500mg IV 4 horas depois da Ifosfamida D1 a 3 Ifosfamida: 1,330 mg/m2 IV D1-3 Mitoxantrona: 8 mg/m2 IV D1 Etoposide: 65 mg/m2 IV D1-3 a cada 21 dias Ref. (21)
Alto Grau
Protocolo de Magrath (Linfoma de Burkitt) Ciclofosfamida: 1,200 mg/m2 IV D1 Doxorrubicina: 40 mg/m2 IV D1 Vincristina: 1.4 mg/m2 IV D1 (mximo de 2 mg) Prednisona: 40 mg/m2 VO D1 -5 Methotrexate: 300 mg/m2 IV D10, em 1 hora, seguido por 60 mg/m2 IV D10 e 11, em 41 horas Resgate com Leucovorin: 15 mg/m2 IV cada 6 horas por 8 doses, iniciando 24 horas aps o methotrexate D12 Ara-C Intratecal: 30 mg/m2 IT D7, somente no ciclo 1 45 mg/m2 IT D7, em todos os ciclos subsequentes
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Methotrexate Intratecal em todos os ciclos: 12.5 mg IT D10 a cada 28 dias Ref. (22) OU Regime A (CODOX-M) Ciclofosfamida: 800 mg/m2 IV D1 e 200 mg/m2 IV D2-5 Doxorrubicina: 40 mg/m2 IV D1 Vincristina: 1.5 mg/m2 IV D1 e 8 no ciclo 1 e D1, 8 e 15 no ciclo 3 Methotrexate: 1,200 mg/m2 IV durante 1 hora, seguido por 240 mg/m2/hora nas 23 horas seguintes D10 Leucovorin: 192mg/m2 IV iniciando na hora 36 aps o incio da infuso e 12 mg/m2 IV a cada 6 horas at os nveis de Methotrexate reduzirem abaixo de < 50 nMol/L Profilaxia do SNC Citarabina: 70 mg IT D1 e 3 Methotrexate: 12 mg IT D15 Regime B (IVAC) Ifosfamida: 1,500 mg/m2 D1-5 (com Mesna) Etoposide: 60mg/m2 IV D1-5 Citarabina: 2 g/m2 IV a cada 12 horas D1 e 2 no total de 4 doses Methotrexate: 12 mg IT D5 Sequncia A/B/A/B - 4 ciclos Ref. (28) Regime de Stanford (Linfoma de Burkitt e pequenas clulas no-clivadas) Ciclofosfamida: 1,200 mg/m2 IV D1 Doxorrubicina: 40 mg/m2 IV D1 Vincristina: 1.4 mg/m2 IV D1 (mximo de 2 mg) Prednisona: 40 mg/m2 VO D1-5 Methotrexate: 3 g/m2 IV em infuso de 6 horas D10
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Resgate com Leucovorin: 25 mg/m2 IV ou VO a cada 6 horas por 12 doses, iniciando 24 horas aps o Methotrexate Methotrexate Intratecal: 12 mg D1 e 10 a cada 21 dias Ref. (23) Stanford V Mustarda Nitrogenada: 6mg/m Doxorrubicina: 25mg/m Vinblastina: 6mg/m Vincristina: 1,4mg/m Bleomicina: 5UI/m Etoposide: 60mg/m Prednisona: 40mg a cada 28 dias
IV D1 IV D1 e 15 IV D1 e 15 IV D8 e 22 IV D8 e 22 IV D15 e 16 VO por dia
Em pacientes acima de 50 anos, a dose da Vinblastina deve ser reduzida para 4mg/m e a dose da Vincristina para 1mg/m nas semanas 9 e 12. Iniciar reduo da dose da prednisona na semana 10. Usar Bactrin Profiltico VO BID e Aciclovir 200mg VO TID. Ref. (24)
Regime de Monoterapia
Rituximabe Rituximabe: 375 mg/m2 IV D1, 8, 15 e 22 Repetir um ciclo adicional. Ref. (25) Fludarabina Fludarabina: 25 mg/m2 IV D1-5 a cada 28 dias Ref. (26)
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Cladribina Cladribina: 0.5-0.7 mg/kg SC D1-5 or 0.1 mg/kg IV D1-7 a cada 28 dias Ref. (27) 1. Colombat P et al. Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation. Blood 2001 Jan 1;97(1):101-6. 2. Marcus R. et al. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. BLOOD 105: 1417, 2005. 3. Hiddemann W; et al. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German LowGrade Lymphoma Study Group.Blood. 2005 Dec 1;106(12): 3725-32. Epub 2005 Aug 25. 4. MacLaughlin P, et al. Fludarabine, mitoxantrone and dexamethasone: an effective new regimen for indolent lymphoma. J Clin Oncol 1996;14:1262-1268. 5. McLaughlin P; et al. Safety of fludarabine, mitoxantrone, and dexamethasone combined with rituximab in the treatment of stage IV indolent lymphoma.Semin Oncol. 2000 Dec;27(6 Suppl 12):37-41. 6. Hochster H, et al. Eficacy of cyclophosphamide (CYC) and fludarabine (FAMP) as first-line therapy of low-grade nonHodgkins lymphoma (NHL). Clood 1994;84(Suppl 1):383a. 7. Falkson CI. A phase II trial in patients with previously trated low-grade lymphoma. Am J Clin Oncol 1996;19:268-270. 8. Bagley CM. Jr et al. Advanced lymphosarcoma: intensive cyclical Combination chemotherapy with cyclophosphamide,
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vincristine, and prednisone. Ann Intern Med 1972:76:227-234. 9. McKelvey EM, et al. Hydroxydaunomycin (Adriamycin) Combination chemotherapy in malignant lymphoma. Cancer 1976;38:1484-1493. 10. Sonnevald P. et al. Companson of doxorubicin and mitoxantrone in the treatment of elderly patients with advanced diffuse non-Hodgkin's lymphoma using CHOP versus CNOP chemotherapy J Clin Oncol 1995;13;25302539. 11. Vose JM, et al. Phase II study of rituximab in combination with CHOP chemotherapy in patients with previously untreated, aggressive non- Hodgkin's lymphoma. J clin Oncol 2001;19:389-397. 12. Vose JM, et al. CNOP for diffuse aggressive non-Hodgkin's lymphoma: the Nebraska lymphoma study group experience. Leuk Lymphoma 2002;43:799-804. 13. Wilson WH, et al. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma. J clin Oncol 1993;11:1573-1582. 14. Wilson WH. Chemotherapy sensitization by rituximab: experimental and clinicai Evidence. Semin Oncol 2000;27 (Suppl 12):30-36. 15. 262. Klimo P, et al. MACOP-B Chemotherapy for the treatment of diffuse large-cell lymphoma. Ann Intern Med 1985;102:596-602. 16. Shipp MA, et al. Identification of major prognostic subgroups of patients with large-cell lymphoma treated with mBACOD or M- BACOD. Ann Intern Med 1986; 104:757-765. 17. Longo DL, et al. Superiority of proMACE- CytaBom over ProMACE-MOPP in the treatment of advanced diffuse aggressive lymphoma: results of a prospective randomized trial. J clin Oncol 1991;9:25-38. 18. Velasquez WS, et al. ESHAP-an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year tbllow-up study. J Clin Oncol 1994;12:1169-1176.
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19. Velasquez WS, et al. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose ara-C and dexamethasone. Blood 1988:71:117-122. 20. Moskowitz C, et al. Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and peripheral blood progenitor cell mobilization regimen for transplant-eligible patients with non-Hodgkin's lymphoma. J Clin Oncol 1999;17:3776-3785. 21. Rodriguez MA, et al. a phase II trial of mesna/ifosfamide, mitoxantrone, and etoposide for refractory lymphoma. Ann Oncol 1995;6:609-611. 22. Magrath I, et al. An effective therapy for both undifferentiated lymphomas and lyrnphohlastic lymphomas in children and young adults. Blood 1984; 63:1102-1111. 23. Berstein JT. et al. Combined modality therapy for adults with small non-cleaved cell lymphoma(Burkitt's and nonBurkitt's types). J Clin Oncol 1986:4:847-858. 24. Bartlett NL, et. al. Brief Chemotherapy, Stanford V And Adjuvant Radiotherapy for Bulky 02 Advanced - Stage Hodgkins disease: A Preliminary Report. J Clin Oncol 1995; 13:1080-1088. 25. McLaughlin P, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy br relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J clin Oncol 1998;16:2825-2833. 26. Falkson Cl. A phase U trial in patients with previously trated low-grade lymphoma. Am J Clin Oncol 1996;19:268-270. 27. Betticher DC, et al. Fewer infections but maintained antitumor activity with lower-dose versus standard-dose cladribine in pretreated low-grade non-Hodgkin's lymphoma. J Clin Oncol 1998:16:850-858. 28. Magrath I, Adde M, Shad A, et al. Adults and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen. J Clin Oncol. 1996; 14:925-34.
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Linfoma de Grandes Clulas B

CHOP + Rituximabe Ciclofosfamida: 750 mg/m IV D1 Doxorrubicina: 50 mg/m IV D1 Vincristina: 1,4 mg/m IV D1 (dose mxima 2 mg) Prednisona: 100 mg VO D1 ao D5 Rituximabe: 375 mg/m IV D1 a cada 21 dias Ref. (01) R-ICE (regime de resgate) Rituximabe: 375mg/m IV D1 Ifosfamida: 5000 mg/m IV contnua por 24 horas D4 Etoposide: 100 mg/m IV D3 ao D5 Carboplatina: AUC 5 IV D4 Mesna: 5000 mg/m IV na mesma bolsa de infuso de Ifosfamida. a cada 14 dias Filgrastima: 5 g/kg D7 ao D14. Ref. (02)
1. Coiffer B, et al. Rituximab plus CHOP in combination with CHOP chemotherapy in patients with diffuse large B-cell lymphoma; an update of the GELA study. N Engl J Med 2002; 346:235-242. 2. Kewalramani T et al.Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. BLOOD 2004; 103-10.
171
Linfoma de Clulas do Manto

Rituximabe + Hyper CVAD Ciclos 1, 3, 5 e 7 Rituximabe: 375mg/m IV D1 Ciclofosfaminda: 300mg/m IV por 3h D1 ao D4 de 12/12h ( total de 6 doses) Mesna: 600mg/m IV em infuso contnua. Iniciar 1h pr ciclofosfamida at 12h aps a ltima dose de ciclofosfamida. Doxorrubicina: 16,6mg/m/dia IV em 24h contnuo D5 ao D7 (iniciar 12h aps ltima dose de ciclofosfamida) Vincristina: 1,4mg/m (mximo de 2mg) IV D5 e D12 Dexametasona: 40mg IV ou VO D2 ao D5 e D12 ao D15 Filgrastima: 5 mcg/kg/dia SC iniciar 24hs aps trmino da quimioterapia Ciclos 2, 4, 6 e 8 Rituximabe: 375mg/m IV D1 Methotrexate: 200mg/m IV D2 por 2h, seguido por 800mg/m IV por 22h Citarabina: 3000 mg/m2 IV por 2h a cada 12h D3 e D4 (total 4 doses) Resgate do MTX com Leucovorin: Iniciar 12hs aps o trmino da infuso: Leucovorin 50mg, seguido de 15mg VO a cada 6h por 8 doses. Nvel srico de Methotrexate deve ser checado 24 e 48h aps o fim da infuso e doses de Leucovorin devem ser aumentadas para 100mg IV a cada 3h se o nvel srico do MTX superar o valor de 1mol/L ou 0,1mol/L em 24 e 48h respectivamente. Ref. (01)
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CHOP + Rituximabe Ciclofosfamida: 750 mg/m IV D1 Doxorrubicina: 50 mg/m IV D1 Vincristina: 1,4 mg/m IV D1 (dose mxima 2 mg) Prednisona: 100 mg VO D1 ao D15 Rituximabe: 375 mg/m IV D1 a cada 21 dias no total de 6 ciclos Ref. (02) FCM + Rituximabe Fludarabina: 25 mg/m IV por 30 min D2 ao D4 Ciclofosfamida: 200 mg/m IV por 4h D2 ao D4 Mitoxantrona: 8mg/m IV por 30 min D2 Rituximabe: 375mg/m IV D1 a cada 28 dias para um total de 4 ciclos Ref. (03) Rituximabe + Hyper CVAD Ciclos 1,3, 5 e 7 Rituximabe: 375mg/m IV D1 Ciclofosfamida: 300mg/m IV por 3h de 12/12h D2 ao D4 Doxorrubicina: 12,7mg/m IV em 24h contnuo D5 ao D7, iniciada 12h aps ltima dose de Ciclofosfamida Vincristina: 1,4mg/m (mximo de 2mg) IV 12h aps a ltima dose de Ciclofosfamida e repetida D12 do ciclo Dexametasona: 40mg IV ou VO D2 ao D5 e D12 ao D15 Observao: 1h antes da admnistrao de Ciclofosfamida deve ser iniciado mesna 600mg/m IV por 24h D2 ao D4 e completada 12h aps a ltima dose de Ciclofosfamida. Ciclos 2, 4, 6 e 8 Rituximabe: 375mg/m IV D1 Methotrexate: 200mg/m IV D2 por 2h, seguido por 800mg/m IV por 22h
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Citarabina: 3000 mg/m2 IV por 2h a cada 12h D3 e D4 Terapia de Resgate: Leucovorin 50mg VO administrado como resgate do Methotrexate 12h aps a infuso deste, seguido de 15mg VO a cada 6h por 8 doses. Ref. (04) Bortezomibe Bortezomibe: 1.3 mg/m2 IV D1, 4, 8 e 11 a cada 21 dias Ref. (5)
1. Romaguera J E et al. High Rate of Durable Remissions After Treatment of Newly Diagnosed Aggressive Mantle-Cell Lymphoma With Rituximab Plus Hyper-CVAD Alternating With Rituximab Plus High-Dose Methotrexate and Cytarabine. J Clin Oncol 23:7013, 2005. 2. Lenz G. et al. Immunochemotherapy With Rituximab and Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Significantly Improves Response and Time to Treatment Failure, But Not Long-Term Outcome in Patients With Previously Untreated Mantle CellLymphoma: Results of a Prospective Randomized Trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol 23:1984, 2005. 3. Forstpointner R et al.The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German LowGrade Lymphoma Study Group. Blood 2004 ; 104 : 3064 71. 4. Romaguera J E et al. Update of the M. D. Anderson Cancer Center experience with hyper-CVAD and rituximab for the treatment of mantle cell and Burkitt-type lymphomas. Clin Lymphoma Myeloma 8:S57, 2007.
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5. Goy AH, et al. Report of a phase II study of proteosome inhibitor bortezomib in patients with relapsed or refractory indolent and aggressive B-cell lytnphomas. Proc Am Soc Clin Oncol 2003;22:570 (abstract 2291).
175
Linfoma Primrio do Sistema Nervoso Central

Protocolo de quimioterapia isolada para linfoma primrio de SNC Methotrexate: 1000 mg/m2 IV D1, D10 e D20 Lomustina: 40 mg/m2 VO D1 Procarbazina: 60 mg/m2 VO D1 ao D7 Metilprednisolona: VO ou IV, 120 mg/m2 em dias alternados D1 ao D20 e 60 mg/m2 D21 ao D45 Methotrexate 15 mg e Citarabina 40 mg IT D1, D5, D10 e D15 Observao: Iniciar Methotrexate aps alcalinizao de urina e pH urinria >7,5. Resgate com leucovorin 25 mg iniciar 24 hs aps o trmino da administrao do Methotrexate IV a cada 6 horas por 3 dias e 10 mg a cada 6 horas por 2 dias aps o Methotrexate IT ou conforme nvel srico de Methotrexate. Dia 45 reavaliao Se doena estvel ou progressiva, suspender protocolo Se resposta parcial ou completa, realizar mais 5 ciclos a cada 6 semanas Methotrexate: 1000 mg/m2 IV D1 Lomustina: 40 mg/m2 VO D1 Procarbazina 60mg/m2 VO D1 ao D7 Methotrexate IT 15 mg e citarabina 40 mg D1 Resgate com Leucovorin: iniciar 24 horas aps o trmino da infuso do Methotrexate IV, Leucovorin 25 mg VO a cada 6 horas por 3 dias. Aps o Methotrexate IT iniciar Leucovorin 10 mg a cada 6 horas por 2 dias. Ref. (01)
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Linfoma Primrio do SNC Methotrexate: 3.5 gm/m2 IV durante 2 horas semanalmente por 5 doses Methotrexate Intratecal: 12 mg IT semanalmente depois do Methotrexate IV Leucovorin: 10 mg IV a cada 6 horas por 12 doses, iniciando 24 horas depois do MTX IV e 10mg IV a cada 12 horas por 8 doses, iniciando 24 horas depois do MTX IT Vincristina: 1.4 mg/m2 IV semanalmente durante o Methotrexate IV Procarbazina: 100 mg/m2/dia VO por 7 dias ciclos 1, 3 e 5 do Methotrexate IV Quando a quimioterapia completada, a radioterapia holocraniana realizada com dose total de 45 cGy. Ref. (02)
Tratamento de pacientes imunocompetentes

Semanas 1, 5 e 9: Procarbazina: 100 mg/m2/dia VO, por 7 dias Vincristina: 1,4 mg/m2/dia IV (no exceder 2,8 mg) Methotrexate: 2,5 g/m2 IV, durante 2 h Leucovorin: 10 mg VO, de 6/6 h, por 12 doses; iniciar 24 h aps o incio do Methotrexate. Semanas 2, 4, 6, 8 e 10: Methotrexate intra-Ommaya: 12 mg/dose Leucovorin: 5 mg VO, de 12/12 h, por 8 doses; iniciar 24 horas aps o Methotrexate. Semanas 3 e 7: Vincristina: 1,4 mg/m2 IV (no exceder 2,8 mg) Methotrexate: 2,5 g/m2 IV, durante 2 h Leucovorin: 10 mg VO, de 6/6 h, por 12 doses;
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iniciar 24 h aps o incio do Methotrexate. Semana 11: - realizar RNM de crebro. Se < 50 anos, prosseguir com RT: RT de crebro total (45 Gy em 25 fraes de 180 cGy/dia); 30 a 40 Gy em globo ocular acometido pelo linfoma. Para pacientes com RC, a RT de crebro total constituda de 36 Gy divididos em 2 fraes dirias de 1,2 Gy (total de 15 dias). Se > 60 anos, administrar doses de Ara-C com as doses descritas para as semanas 16 e 19. Semana 16: realizar RNM de crebro e administrar Ara-C: 2g/m2/dia IV, durante 3 horas, por 2 dias. Semana 19: Ara-C: 3 g/m2/dia IV, em 3 horas, por 2 dias. Ref. (03)
1. Hoang-Xuan et al. Chemotherapy alone as inicial treatment for primary CNS lymphoma in patients older than 60 years: a multicenter phase II study of the european organization for research and treatmnet of cncer brain tumor group. JCO, 2003;21:2726-2731. 2. Abrey L, et al. Treatment for primary CNS lymphoma; the next step. J Clin Oncol 2002;18:3144-3150. 3. De Angelis LM, Tong WP, Lin S, Fleisher M, et al. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol 2002; 20: 4643-8.
178
Mieloma Mltiplo
Bortezomibe + Dexametasona (Vel/Dex) Bortezomibe: 1,3 mg/m2 IV pulso D1, D4, D8 e D11 Dexametasona: 40 mg/dia VO D1 ao D4 nos ciclos 1,2,3 e 4 Dexametasona 40 mg/dia VO D1-4 e D9-12 nos ciclos 1 e 2 a cada 21 dias no total de 4 ciclos Ref. (01) Bortezomibe + Doxorrubicina + Dexametasona (PAD) Bortezomibe: 1,3 mg/m IV pulso D1, D4, D8 e D11 Doxorrubicina: 9 mg/m IV em 1h D1 ao D4 Dexametasona: 40 mg VO D1 ao D4 para todos os ciclos; D8 ao D11 e D15 ao D18 somente para o ciclo 1. a cada 21 dias no total de 4 ciclos Ref. (02) VMP Bortezomibe: 1,3 mg/m2 IV D1, D4, D8, D11, D22, D25, D29 e D32 (ciclos 1-4) e D1, D8, D22 e D29 (ciclos 5-9) Melfalano: 9 mg/m2 e prednisona 60 mg/m2 VO D1 ao D4 a cada 6 semanas no total de 9 ciclos Total : 9 x ciclos de 6 semanas (54 sem) Ref. (03) CVD Bortezomibe: 1,3 mg/m2 IV em pulso D1, D4, D8 e D11 Dexametasona: 40mg/dia VO D1 e D2, D4 e D5, D8 e D9, D11 e D12 Ciclofosfamida: 500mg/dia VO D1, D8 e D15 a cada 21 dias no total mximo de 9 ciclos Ref. (04)
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Cybord 1 cohort Bortezomibe: 1,3 mg/m2 IV em pulso D1, D4, D8 e D11 Dexametasona: 40mg VO D1 ao D4, do D9 ao D12 e D17 ao D20 Ciclofosfamida: 300mg/m2/dia VO D1, D8, D15 e D22 a cada 28 dias 2 cohort Bortezomibe: 1,5 mg/m2 IV em pulso D1, D8, D15 e D22 Dexametasona: 40mg/dia VO D1 ao D4, D9 ao D12 e D17 ao D20 para os ciclos 1 e 2 e semanalmente nos ciclos 3 e 4. Ciclofosfamida: 300mg/m2/dia VO D1, D8, D15 e D22 a cada 28 dias Ref. (05)
Regimes Combinados
MP Melfalano: 8-10 mg/m2 VO D1-4 Prednisona: 60 mg/m2 D1-4 a cada 42 dias Ref. (06) MPR Melfalano: 0.18 mg/kg por 4 dias Prednisona: 2 mg/kg/dia por 4 dias Revlimide: 10 mg/dia por 21 dias a cada 4-6 semanas Ref. (07) MPT Melfalano: 0.25 mg/kg D1 a 4 Prednisona: 1.5 mg/kg D1 a 4 a cada 4 a 6 semanas Talidomida: 50-100 mg/dia continuamente. Ref. (08)
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VAD Vincristina: 0.4 mg/dia IV em infuso contnua D1-4 Doxorrubicina: 9 mg/m2/dia IV em infuso contnua D1-4 Dexametasona: 40 mg VO D1-4, 9-12 e 17-20 a cada 28 dias Ref. (09) Talidomida + Dexametasona Talidomida: 200 mg/dia VO Dexametasona: 40 mg/dia VO D1-4, 9-12 e 17-20 a cada 28 dias (Celgene Talidomida PI.) Ref. (10) Bortezomibe + Doxorrubicina Lipossonal Peguilada Bortezomibe: 1.3 mg/m2 IV pulso D1, 4, 8 e 11 Doxorrubicina: 30 mg/m2 IV D4, depois do Bortezomibe a cada 21 dias Ref. (11) Lenalidomida + Dexametasona Lenalidomida: 25 mg/dia VO D1-21 Dexametasona: 40 mg/dia VO D1-4, 9-12 e 17-20 (nos primeiros 4 ciclos) seguido por 40 mg/dia VO D1-4 ou 40 mg/dia VO D1, 8, 15 e 22. a cada 28 dias (Celgene Revlimid PI) Ref. (12)
Regimes de Monoterapia
Dexametasona Dexametasona: 40 mg IV ou VO D1-4, 9-12 e 17-20 a cada 21 dias Ref. (13)
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Lenalidomida Lenalidomida: 30 mg VO D1 a 21 a cada 28 dias Ref. (14) Melfalano Melfalano: 90-140 mg/m2 IV D1 a cada 28-42 dias Ref. (15) Talidomida Talidomida: 200-800 mg VO dia Continuar tratamento at progresso da doena ou toxicidade proibitiva. Ref. (16) Bortezomibe Bortezomibe: 1.3 mg/m2 IV D1, 4, 8 e 11 a cada 21 dias
Ref. (17)
Se ocorrer doena progressiva aps 2 ciclos ou doena estvel aps 4 ciclos pode se acrescentar Dexametasona 20mg VO diariamente nos dias de descanso aps o Bortezomibe. Interferon -2b Interferon -2b: 2 milhes IU SC ou IM. 3 vezes semanalmente Usar como terapia de manuteno em pacientes com resposta significativa com a quimioterapia de induo. Ref. (18) 1. Jean-Luc Harousseau et al. Bortezomib Plus Dexamethasone Is Superior to Vincristine Plus Doxorubicin Plus Dexamethasone As Induction Treatment Prior to Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: Results of the IFM 2005-01 Phase III Trial. JCO 2010. JCO October 20, 2010 vol. (28) : 4621-4629 2. Oakervee HR et al. BR J Haematol.2005;129:755-62 3. San Miguel, JF et al. Bortezomib plus Melphalan and
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Prednisone for Initial Treatment of Multiple Myeloma. N Engl J Med 2008; 359:906-917. 4. Davies, FE et al. The combination of cyclophosphamide, velcade and dexamethasone (CVD) induces high response rates with comparable toxicity to velcade alone (V) and velcade plus dexamethasone (VD). Haematologica 2007;92:1149-1150. 5. Reeder et al. Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia (2009) 23, 13371341. Craig B. Reeder, et al. Once- versus twice-weekly bortezomib induction therapy with CyBorD in newly diagnosed multiple myeloma. Blood, Apr 2010; 115: 3416 3417. 6. Southwest Oncology Group study. Remission maintenance therapy for multiple myeloma. Arch Intern Med 1975:135:147-152. 7. Palumbo A, Falco P, Falcone A, Corradini P, Di Raimondo F, Giuliani N, Rossi G, Morabito F, Canepa L, Gozzetti A, Ambrosini MT, Zeldis J, Knight R, Foa R, Boccadoro M, Petrucci MT. Oral Revlimid plus melphalan and prednisone (R-MP) for newly diagnosed multiple myeloma: Results of a multicenter phase I/II study(asbstract). Blood: ASH Annual Meeting Proceedings 2006: 108(11 Part l of2): 240a, abstract #0800. 8. Palumbo A. Bringhen S, Caravita T. Merla E, Capparella V, Callea V, Cangialosi C Grasso M, Rossini F, Galli M, Catalno L, Zamagni E, Petrucci MT, De Stefano V, Ceccarelli M, Ambrosini MT, Avonto I, Falco P, Ciccone G, Liberati AM, Musto P, Boccadoro M, Italian Multiple Myeloma Network GIMEMA. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: Randomised controlled trial. Lancet 2006: 367(9513):825-31. 9. Barlogie B, et al. Effective treatment of advanced multiple mueloma refractory to alkylating agents. N Engl J Med 1984;310:1353-1356. 10. Rajkumar SV, et al. Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. J Clin Oncol 2002;20:4319-4323.
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11. Orlowaki RX Peterson BI, Caligiuri MA, et al. Bortezomib and pegylated liposomal doxorubicin as initial therapy for adult patients with symptomatic multiple myeloma: CALGB study 10301 Pster presented at the 10th intemational myeloma Workshop, 2005, april 10-14, Sydney, Austrlia. 12. Rajkumar SV, Jacobus S, Callander N, Fonseca R, Vesole D, Williams M. Abonour R, siegel D, Greipp P. Phase III trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma (E4A03): A trial coordinated by the Eastern Cooperative Oncology Group (Abstract). Proceedings of the 43rd Annual Meeting of the American Society of clinicai oncology 2007b: june 1-5: Chicago. IL: Abstract #LBA8025. 13. Alexanian R, et al. High-dose glucocorticoid treatment of resistant myeloma. Ann Intern Med 1986:105:8-11. 14. Richardson PG, blood E, MTsiades CS, Jagannath S, Zeldenrust S, Alsina M. Schlossman RL, Rajkumar SV, Desikan KR, Hideshima T Munshi N, Kelly colson k, doss D, McKenney M, Gorelik S, Warren D, Freeman A, Rich R, Wu A Olesnyckj M, Wride K, Dalton W, Zeldis J, Knight R, Weller E. Anderson KC. A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood :006;108(10):3458-64. 15. Cunningham D. et al. High-dose melphalan for multiple myeloma: long-tenn follow-up data. J Clin Oncol 1994;12:7&l-768. 16. Singhal S, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999;34P1565-1571. 17. Richardson P. et al. A phase II study of botezomib in relapsed. refractory myeloma. N Engl J Med 2003;348:2609-2617. 18. Browman GP. et al. Randomized trial of interferon maintenance in multiple myeloma: a study of the National Cancer Institute of Canada Clinicai Trials Group. J Clin Oncol 1995;13:2354-2360. 312.
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Sndrome Mielodisplsica
Azacitidina Azacitidina: 75 mg/m2 SC diariamente por 7 dias a cada 6 semanas. Pacientes devem ser tratados por pelo menos 4 ciclos. Ref. (1) Decitabina Decitabina: 15 mg/m2 IV infuso contnua de 3 horas a cada 8 horas por 3 dias a cada 4 semanas. Pacientes devem ser tratados por pelo menos 4 ciclos. Ref. (2) Decitabina: 20 mg/m2 IV infuso contnua por 1h por 5 dias a cada 4 a 6 semanas. Pacientes devem ser tratados por pelo menos 4 ciclos. Ref. (3) Lenalidomida Lenalidomida: 10 mg VO dia A dose continuada ou modificada baseada em achados clnicos e laboratoriais. Ref. (4)
1. Silverman LR, et al. Further analysis of trials with azacitidine in patients with myelodysplastic syndrome. studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol 2006:324: 3895-3903. 2. Kantarjian H, et al. Decitabine improves patient outcomes in myelodysplastic syndromes. Cancer 2006; 106:1794-1780.
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3. Kantarjian H, et al. Decitabine dosng schedules. sem in Hematolqly 2005;32 (suppl):sl7-522. 4. Galili N., et al. Immunomodulatory drugs in myelodysplastic syndromes Expert Opin Investig Drugs 2006;15:805-813.
186
Macroglobulinemia de Waldestrn
Bortezomibe e Rituximabe Bortezomibe: 1,6 mg/m2 IV semanalmente D1, D8, D15. Rituximabe: 375 mg/m2 IV semanalmente no ciclo 1 e 4. a cada 28 dias no total de 6 ciclos Ref. (01) Bendamustina e Rituximabe Rituximabe: 375 mg/m2/dia IV D1 Bendamustina: 90 mg/m2/dia IV durante 30 minutos D1 e D2 a cada 28 dias no total de 4 ciclos Ref. (02)
1. Irene M. Ghobrial et al. Phase II trial of weekly bortezomib in combination with rituximab in untreated patients with Waldenstrm Macroglobulinemia. American Journal of Hematology. 2010, 85: 670674. 2. Mathias J. Rummel, Salah E. Al-Batran, Soo-Z. Kim, et al. Bendamustine Plus Rituximab Is Effective and Has a Favorable Toxicity Profile in the Treatment of Mantle Cell and Low-Grade Non-Hodgkin's Lymphoma Journal of Clinical Oncology, Vol 23, No 15, 2005: pp. 3383-3389.
187
Leucemia de Clulas Cabeludas (Tricoleucemia)

Tratamento padro: Cladribina: 0,1 mg/kg/dia IV infuso contnua por 7 dias (ciclo nico). Opes do uso de cladribina: a. 0,14 mg/Kg/dia IV, infundir durante 2h por 5 dias b. 0,14 mg/Kg IV, infundir durante 2h uma vez por semana c. 0,14 mg/Kg SC, uma vez por semana Avaliar associao de rituximabe 375 mg/m2, IV na HCL variante Ref. (01)
1. Saven A, et al. Blood 1998;92:1918-26. Lauria F, Bocchia M, Marotta G, Raspadori D, Zinzani PL, Rondelli D. Weekly administration of 2-chlorodeoxyadenosine in patients with hairy-cell leukemia is effective and reduces infectious complications. Haematologica. 1999;84(1):2225. Golomb HM. Hairy cell leukemia: treatment successes in the past 25 years. J Clin Oncol. 2008;26(16):26072609. Robak T, Jamroziak K, Gora-Tybor J, et al. Cladribine in a weekly versus daily schedule for untreated active hairy cell leukemia: final report from the Polish Adult Leukemia Group (PALG) of a prospective, randomized, multicenter trial. Blood. 2007;109(9):36723675. Juliusson G, Liliemark J. Purine analogues: rationale for development, mechanisms of action, and pharmacokinetics in hairy cell leukemia. Hematol Oncol Clin North Am. 2006;20(5):10871097. Zinzani PL, Tani M, Marchi E, et al. Long-term follow-up of frontline treatment of hairy cell leukemia with 2chlorodeoxyadenosine. Haematologica. 2004;89(3):309313.
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Zenhausern R, Schmitz SF, Solenthaler M, et al. Randomized trial of daily versus weekly administration of 2-chlorodeoxyadenosine in patients with hairy cell leukemia: a multicenter phase III trial (SAKK 32/98). Leuk Lymphoma. 2009:111.
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Leucemias Agudas
Quimioterapia de Induo
Regime de Linker Daunorrubicina: 50 mg/m2 IV a cada 24 horas D1-3 Vincristina: 2 mg IV D1,8, 15 e 22 Prednisona: 60 mg/m2 VO dividido em 3 doses D1-28 L-Asparaginase: 6,000 U/m2 IM D17-28 Se a medula ssea foi positiva para leucemia residual, Daunorrubicina: 50 mg/m2 IV D15 Se a medula ssea no dia 28 for positiva para leucemia residual, Daunorrubicina: 50 mg/m2 IV D29 e 30 Vincristina: 2 mg IV D29 e 36 Prednisona: 60 mg/m2 VO D29-42 L-Asparaginase: 6,000 U/m2 IM D29-35 Ref. (1,2)
Terapia de Consolidao
Regime de Linker Tratamento A (ciclo 1, 3, 5 e 7) Daunorubicina: 50 mg/m2 IV D1 e 2 Vincristina: 2mg IV D1 e 8 Prednisona: 60 mg/m2 VO D1-14 L-Asparaginase:12,000 U/m2 D2, 4, 7, 9, 11 e 14 Tratamento B (ciclo 2, 4, 6 e 8) Teniposide: 165 mg/m2 IV D1,4, 8 e 11 Citarrabina: 300 mg/m2 IV D1, 4, 8 e 11 Tratamento C (ciclo 9) Methotrexate: 690 mg/m2 IV durante 42 horas Leucovorin: 15 mg/m2 IV a cada 6 horas 12 doses iniciando na hora 42 Ref. (1,2)
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Terapia de Manuteno
Regime de Linker Methotrexate: 20 mg/m2 VO semanalmente 6-Mercaptopurina: 75 mg/m2 VO contnuo por um total de 30 meses aps a resposta completa. Profilaxia SNC Radioterapia craniana: 1,800 cGy em 10 redues durante 12 a 14 dias Methotrexate: 12 mg IT semanalmente por 6 semanas Iniciar dentro de uma semana aps resposta completa Em pacientes com envolvimento do SNC no diagnstico a quimioterapia intratecal deve ser iniciada durante a quimioterapia de induo Methotrexate: 12 mg IT semanalmente por 10 doses Radioterapia craniana: 2,800 cGy Ref. (1,2)
Terapia de Induo
Regime de Larson Induo (semana 1-4) Ciclofosfamida: 1,200 mg/m2 IV D1 Daunorrubicina: 45 mg/m2 IV D1-3 Vincristina: 2 mg IV D1, 8, 15 e 22 Prednisona: 60 mg/m2/dia VO D1-21 L-Asparaginase: 6,000 IU/m2 SC D5, 8, 11, 15, 18, 22 Intensificao precoce (semana 5-12) Methotrexate: 15 mg IT D1 Ciclofosfamida: 1,000 mg/m2 IV D1 6-Mercaptopurina: 60 mg/m2/dia VO D1-14 Citarabina: 75 mg/m2 IV D1-4 e D8-11 Vincristina: 2 mg IV D15 e 22 L-Asparaginase: 6,000 IU/m2 SC D15, 18, 22 e 25
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Profilaxia do SNC e manuteno interina (semana 13-25) Radioterapia craniana: 2,400 cGy D1-12 Methotrexate: 15 mg IT D1, 8, 15, 22 e29 6-Mercaptopurina: 60 mg/m2/dia VO D1-70 Methotrexate: 20 mg/m2 VO D36, 43, 50, 57 e 64 Intensificao Tardia (semana 26-33) Doxorrubicina: 30 mg/m2 IV D1, 8 e 15 Vincristina: 2 mg IV D1, 8 e15 Dexametasona: 10 mg/m2/dia VO D1-14 Ciclofosfamida: 1 ,000 mg/m2 IV D29 6-Tioguanina: 60 mg/m2/dia VO D29 - 42 Citarrabina: 75 mg/m2 D29, 32, 36-39 Manuteno Prolongada (continuar at 24 meses aps o diagnstico) Vincristina: 2mg IV D1 Prednisona: 60 mg/m2/dia VO D1-5 Methotrexate: 20 mg/m2 VO D1, 8, 15 e 22 6-Mercaptopurina: 80 mg/m2/dia VO D1-28 Repetir ciclo de manuteno a cada 28 dias. Ref. (3) Regime Hyper-CVAD Ciclofosfamida: 300 mg/m2 IV durante 3 horas a cada 12 horas por 6 doses D1-3 Mesna: 600 mg/m2 IV durante 24 horas D1-3, terminando 6 horas apos a ltima dose de Ciclofosfamida Vincristina: 2 mg IV D4 e 11 Doxorrubicina: 50 mg/m2 IV D4 Dexametasona: 40 mg VO ou IV D1-4 e 11-14 Alternando ciclos a cada 21 dias com: Methotrexate: 200 mg/m2 IV durante 2 horas, seguido por 800 mg/m2 IV durante 24 horas no D1 Leucovorin: 15 mg IV a cada 6 horas por 8 doses, iniciando 24
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horas aps o trmino de infuso do Methotrexate Citarabina: 3,000 mg/m2 IV durante 2 horas a cada 12 horas por 4 doses D2-3 Metilprednisolona: 50 mg IV BID D1-3 Alternar 4 ciclos de hiper-CVAD com 4 ciclos de Methotrexate em dose alta Ref. (4). Profilaxia SNC Methotrexate: 12mg IT D2 Citarabina: 100 mg IT D8 Repetir a cada ciclo de quimioterapia, dependendo do risco de doena no SNC.
1. Linker CA, et al. Improved results of treatment of adult acute lymphoblastic leukemia. Blood 1987:69:1242-1248. 2. Linker CA, et al. treatmentof adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report. Blood 1991;75:2814-2822. 3. Larson R, et al. A five-drug regimen remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: Cancer an Leukemia Group B study 8811, Blood 1995;85:2025-2037. 4. Kantarjian H, et al. Results of treatment with hyper- CVAD, a dose-intensive regimen in adult acute lymphoblastic leukemia. J Clin Oncol 2000;18:547-561.
193
Leucemia Mielide Crnica

Imatinibe Imatinibe: 400 mg/dia VO Ref. (1) Dasatinibe Dasatinibe: 70mg VO BID Dasatinibe: 100mg VO MID Ref. (2) Nilotinibe Nilotinibe: 400mg VO BID Ref. (3) Hidroxiuria Hidroxiuria: 40 mg/kg/dia VO Ref. (4) 1. Kantarjian H, et al. Hematologic and Cytogenetic Responses to Imatinib Mesylate in Chronic Myelogenous Leukemia. NEJM.2002;346:645-52. 2. Shah NP; Kantarjian HM; Kim DW; et al. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and intolerant chronic-phase chronic myeloid leukemia.J Clin Oncol. 2008 Jul 1;26(19):3204-12. 3. Av a i l a b l e f r o m t h e U S F D A w e b s i t e a t : <www.fda.gov/cder/foi/label/2007/022068lbl.pdf 4. Hehlmann R, et al. Randomized comparison of interferonalpha with busulfan and hydroxyurea in chronic myelogenous leukemia. The German CML Study Group. Blood 1994;84:4064-4077.
194
Leucemia Linftica Crnica

CVP Ciclofosfamida: 400 mg/m VO D1 ao D5 (ou 800 mg/m IV D1) Vincristina: 1,4 mg/m IV D1 (dose mxima 2 mg) Prednisona: 100 mg/m VO D1 ao D5 a cada 21 dias Ref. (1) FC Ciclofosfamida: 1000 mg/m IV D1 Fludarabina: 20 mg/m IV D1 ao D5 a cada 21 ou 28 dias Ref. (2) Clorambucil Clorambucil: 6 a 14 mg/dia VO como terapia de induo e ento 0,7 mg/kg VO por 2 a 4 dias a cada 21 dias Ref. (3) Fludarabina Fludarabina: 20 a 30 mg/m IV D1 ao D5 a cada 28 dias FP Fludarabina: 30 mg/m IV D1 ao D5 Prednisona: 30 mg/m IV D1 ao D5 a cada 28 dias CP Clorambucil: 30 mg/m VO D1 Prednisona: 80 mg VO D1 ao D5 a cada 28 dias
Ref. (4)
Ref. (5)
Ref. (6)
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FR Fludarabina: 30 mg/m IV D1 ao D5 Rituximabe: 375 mg/m IV D1, D3 e D5 a cada 28 dias FCR Ciclo 1: Fludarabina: 25 mg/m IV D2-D4 Ciclofosfamida: 250 mg/m IV D2-D4 Rituximabe: 375 mg/m2 D1 Ciclo 2-6: Fludarabina: 25 mg/m IV D1-D3 Ciclofosfamida: 250 mg/m IV D1-D3 Rituximabe: 500 mg/m2 D1 a cada 28 dias FCR-Lite Ciclo 1: Rituximabe: 375 mg/m2 IV D1 Rituximabe: 500 mg/m2 IV D14 Fludarabina: 20 mg/m2 IV D2 ao D4 Ciclofosfamida: 150 mg/m2 IV D2 ao D4 Ciclos 2-6: Rituximabe: 500 mg/m2 IV D1 e no D14 Fludarabina: 20 mg/m2 IV em 30 minutos D1 ao D3 Ciclofosfamida: 150 mg/m2 IV em 60 minutos D1 ao D3 Manuteno: Rituximabe 500 mg/m2 IV a cada 3 meses at recidiva Ref. (9)
Ref. (7)
Ref. (8)
Alentuzumabe Alentuzumabe: 3,10 e 30 mg IV em 2 horas D1, D2 e D3 respectivamente.
196
Alentuzumabe: 30 mg IV trs vezes por semana at o total de 12 semanas (incluindo a semana com escalonamento) Ref. (10) Rituximabe e Alentuzumabe Ciclo 1: Rituximabe: 375 mg/m2 IV no D1 e 500 mg/m2 IV D8, D15 e D22 Alentuzumabe: 30 mg/dia IV em infuso contnua D2 ao D7 Alentuzumabe: 30 mg/dia SC D10, D12, D17, D19, D24 e D26 Ciclo 2-3 (opcional): Rituximabe: 500 mg/m2 IV D1, D8, D15 e D22 Alentuzumabe: 30 mg/dia SC D3, D5, D10, D12, D17, D19, D24 e D26 Ref. (11) Bendamustina e Rituximabe Ciclo 1: Bendamustina: 70 mg/m2 IV D1 e D2 Rituximabe: 375 mg/m2 IV D1 Ciclos2-6: Bendamustina: 70 mg/m2 IV D1 e D2 Rituximabe: 500 mg/m2 IV D1
Ref. (12)
Rituximabe e Corticide em Dose Alta Ciclos 1-3: Solumedrol: 1000 mg/m2 IV em 90 minutos uma vez ao dia D1 ao D5 Rituximabe: 375 mg/m2 IV semanalmente por 4 semanas Ref. (13) OFAR Ciclos 1-6: Oxaliplatina: 25 mg/m2 IV D1 ao D4 Fludarabina: 30 mg/m2 IV D2 e D3 Citarabina: 1000 mg/m2 IV D2 e D3
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Rituximabe: 375 mg/m2 IV D3 (Ciclo 1) e D1 (Ciclos 2-6) Ref. (14) CFAR Ciclo 1: Ciclofosfamida: 250 mg/m2 IV D3 ao D5 Fludarabina: 25 mg/m2 IV D3 ao D5 Alentuzumabe: 30 mg IV D1, D3 e D5 Rituximabe: 375 mg/m2 IV D2 (ciclo 1) e 500mg/m2 IV D2 (ciclo 2-6) Ref. (15) 1. Raphael B, et al. Comparison of chlorambucil and prednisone versus cyclophosphamide, vincristine, and prednisone as initial treatment for chronic lymphocytic leukemia: longterm follow-up of an Eastern Cooperative Oncology Group randomized clinical trial. J clin Oncol 1991:9:770-776. 2. Keating MJ, et al. Long-term follow-up of patients with chronic lymphocytic leukemia (CLL) receiving fludarabine regimens as initial therapy. Blood 1998;92:1165-1171. 3. Dighiero G, et al. Chlorambucil in indolent chronic lymphocytic leukemia French cooperative Group on chronic Lymphocytic leukemia. N Engl J Med 1998;338:1506-1514. 4. Keating MJ, et al. Long-term follow-up of patients with chronic lymphocytic leukemia (CLL) receiving fludarabine regimend as initial therapy. Blood 1988;92:1165-1171. 5. OBrien S, et al. Results of fludarabine and prednisone therapy in 264 patients with chronic lymphocytic leukemia with multivariate analysisderived prognostic model for response to treatment. Blood 1993;82:1695-1700. 6. Raphael B, et al. Comparison of chlorambucil and prednisone versus cyclophosphamide, vincristine, and prednisone as initial treatment for chronic lymphocytic leukemia: longterm follow- up of an Eastern Cooperative Oncology Group randomized clinical trial. J clin Oncol 1991:9:770-776. 7. Byrd JC, et al. Randomized phase 2 study of fludarabine with
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concurrent versus sequential treatment with rituximab in symptomatic untreated patients with B-cell chronic lymphocytic leukemia: results from Cancer and Leukemia Group B9712. Blood 2003;101:6-14. 8. Keating M, et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for CLL. J Clin Oncol 2005;22:4079-4088. 9. Fonn KA, et al. Chemoimmunotherapy with low dose fludarabine and cyclophosphamide and high dose rituximab in previously untreated patients with chronic lymphocytic leukemia. J Clin Oncol 2009; 27:498-503. 10. Hillmen P, et al. Alemtuzumab compared with chlorambucil as first line therapy for chronic lymphocytic leukemia. J Clin Oncol 2007;25:5616-5623. 11. Faderl S, et al. Alemtuzumab by continuous intravenous infusion followed by subcutaneous injection plus rituximab in the treatment of patients with chronic lymphocytic leukemia recurrence. Cancer 2010; 116:2360-2365. 12. Firsten K, et al . Bendamustine in combination with rituximab for patients with relapsed chronic lynphocytic leukemia: a multicenter phase II Trial of the German CLL Study Group. Blood 2008; 112:Abstract 330. 13. Castro JE, et al. Rituximab in combination with high-dose methylprednisolone for the treatment of fludarabine refractory high-risk chronic lymphocytic leukemia. Leukemia 2008; 22:2048-53. 14. Tsimberidou AM, et al. Phase I-II study of oxaliplatin, fludarabine, cytarabine, and rituximab combination therapy in patients with Richter's syndrome or fludarabinerefractory chronic lymphocytic leukemia. J Clin Oncol 2008; 26:196-203. 15. Badoux XC, et al. Chemoimmunotherapy with Cyclophosphomide, Fludarabine, Alemtuzumab and Rituximab (CFAR) Is Effective in Relapsed Patients with Chronic Lymphocytic Leukemia (CLL). Blood 2009; 114:Abstract 3431.
199
Sarcomas de Partes Moles

AIM- Doxorrubicina, Ifosfamida e Mesna Doxorrubicina: 75 mg/m2/ciclo IV em pulso divididos entre D1 a D3 Ifosfamida: IV 69g/m2/ciclo, divididos entre D1 a D3 Mesna a cada 28 dias para um total de 4 ciclos Ref. (1) AIM- Doxorrubicina, Ifosfamida e Mesna Doxorrubicina: 30 mg/m2/dia IV pulso D1 e D2 Ifosfamida: 3,75g/m2/dia IV D1 e D2 Mesna: 750 mg/m2 IV imediatamente antes, 4 horas e 8 horas aps administrao da Ifosfamida a cada 21 dias para um total de 3 ciclos Ref. (2) MAID- Mesna, Doxorrubicina, Ifosfamida e Dacarbazina Doxorrubicina: 60 mg/m2 IV contnua D1 ao D4 Dacarbazina: 1g/m2 IV contnua D1 ao D4 Ifosfamida: 6 g/m2 IV D1 ao D3 associada a Mesna Mesna: 10.000 mg/m2 D1 ao D4 a cada 21 dias por um total de 4 ciclos Ref. (3) Gencitabina e Docetaxel Gencitabina: 900 mg/m2 IV D1 e D8 Docetaxel: 100 mg/m2 IV D8 a cada 21 dias por um total de 6 ciclos Ref. (4)
200
Ifosfamida e Epirrubicina Ifosfamida: 1,8g/m2/dia IV D1 ao D5 (dose total por ciclo de 9g/m2) Mesna: IV pulso na dose equivalente a 20% da dose de Ifosfamida, a ser administrada antes, 4 horas e 8 horas aps infuso de Ifosfamida Epirrubicina: 60mg/m2/dia IV pulso D1 e D2 (dose mxima por ciclo de 120 mg/m2) a cada 21 dias para um total de 5 ciclos Ref. (5) AD- Doxorrubicina e Dacarbazina Doxorrubicina: 60 mg/m2 IV contnua D1 ao D4 Dacarbazina: 1g/m2 IV contnua D1 ao D4 a cada 21 dias para um total de 4 ciclos Ref. (6) CYVADIC- Ciclofosfamida, Vincristina, Doxorrubicina e Dacarbazina Doxorrubicina: IV 120 mg/m2 D1 Dacarbazina: 250 mg/m2/dia D1 ao D5 Ciclofosfamida: 500 mg/m2 IV D1 Vincristina: 5mg/m2 IV D1 a cada 28 dias para um total de 4 ciclos Ref. (7) VAC/IE Vincristina, Doxorrubicina e Ciclofosfamida alternados com Ifosfamida e Etoposide Ciclo A: Vincristina: 2 mg/m2 IV D1 (dose mxima de 2mg) Doxorrubicina: IV 75 mg/m2 em infuso rpida D1 Ciclofosfamida: 1200 mg/m2 D1, seguida de Mesna (dose no especificada). A dose cumulativa mxima de doxorrubicina de 375 mg/m2. Uma vez atingida, deve-se substituir a Doxorrubicina por Dactinomicina 1,25 mg/m2 IV D1 iniciada no ciclo 11.
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Ciclo B: Ifosfamida: 1,8 g/m2/dia IV D1 ao D5 (concomitante mesna) Etoposide: 100 mg/m2/dia IV D1 ao D5. Alternar os ciclos A e B a cada 3 semanas, por um total de 17 ciclos. Durao estimada da QT: 49 semanas Ref. (8) IE- Ifosfamida e Etoposide Etoposide: 100mg/m2/dia IV D1 ao D5 durante 2 horas, seguido imediatamente pela Ifosfamida Ifosfamida: 1,8g/m2/dia IV D1 ao D5 durante 2 horas (administrada concomitante Mesna) Mesna: 60% da dose da Ifosfamida. a cada 21 dias por um total de 5 ciclos Ref. (9) VAC- Vincristina, Dactinomicina e Ciclofosfamida Regime de Induo (semanas 1 a 17): Vincristina: 1,5 mg/m2 (mximo de 2 mg) IV pulso D1 das semanas 1 a 13 e, posteriormente, uma dose na semana 17 Dactinomicina: 0,015 mg/Kg/dia (mximo de 0,5mg) IV pulso D1 ao D5 das semanas 1, 4, 7 e 17 Ciclofosfamida: 2,2 g/m2 IV D1 das semanas 1, 4, 7, 10, 13 e 17 Regime de manuteno (semanas 21 a 44): Vincristina: 1,5 mg/m2 (mximo de 2 mg) IV pulso D1 das semanas 21 a 26, 30 a 35 e 39 a 44 Dactinomicina: 0,015 mg/Kg/dia (mximo de 0,5mg) IV pulso D1 ao D5 das semanas 21, 24, 30, 33, 39 e 42 Ciclofosfamida: 2,2 g/m2 IV D1 das semanas 21, 24, 30, 33, 39 e 42 Ref. (10)
202
Doxorrubicina Lipossomal Doxorrubicina lipossomal: 50 mg/m2 IV em 1 hora a cada 4 semanas Ref. (11) Imatinibe Imatinibe: 400mg VO 1 vez ao dia, podendo-se aumentar a dose para 2 x ao dia, contnuo Ref. (12) Sunitinibe Sunitinibe: 50 mg por dia VO durante 4 semanas a cada 6 semanas Ref. (13) Temozolomida Temozolomida: 200 mg/m2 (1a dose) VO D1 28 dias Temozolomida: 90 mg/m2 (2a dose em diante) VO 12/1 2 horas D1 a D5 28 dias Ref. (14) Gencitabina Gencitabina: 1000 mg/m2 IV D1 semanal* * No perodo de induo, a quimioterapia aplicada por 7 semanas, seguidas por uma de descanso. Na fase seguinte, de manuteno, a quimioterapia aplicada por 3 semanas, seguidas por uma de descanso. Ref. (15) Paclitaxel Paclitaxel: 175 mg/m2 Ref. (16)
IV
D1
21 dias
203
1. S. R. Grobmyer, R. G. Maki, G. D. Demetri, M. Mazumdar4, E. Riedel, M. F. Brennan1 & S. SingerDepartments of Surgery, Medicine and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY; 4Department of Medicine, Dana Farber Cancer Institute, Boston, MA, USA. Annals of Oncology 15: 16671672, 2004. 2. Karen Antman, John Crowley, Stanley P. Balcerzak, et al. An Intergroup Phase III Randomized Study of Doxorubicin and Dacarbazine With or Without Ifosfamide and Mesnain Advanced Soft Tissue and Bone Sarcomas Journal of Clinical Oncology, Vol 11, No 7 (July), 1993: pp 1276-1285. 3. Karen Antman, John Crowley, Stanley P. Balcerzak, et al. An Intergroup Phase III Randomized Study of Doxorubicin and Dacarbazine With or Without Ifosfamide and Mesnain Advanced Soft Tissue and Bone Sarcomas Journal of Clinical Oncology, Vol 11, No 7 (July), 1993: pp 1276-1285. 4. Robert G. Maki, J. Kyle Wathen, Shreyaskumar R. Patel, et al. Phase II Study of Gemcitabine and Docetaxel Compared With Gemcitabine Alone in Patients With Metastatic Soft Tissue Sarcomas: Results of Sarcoma Alliance for Research Through Collaboration Study 002 Journal of Clinical Oncology, Vol 25, No 19 (July 1), 2007: pp. 2755-2763. 5. Sergio Frustaci, Franco Gherlinzoni, Antonino De Paoli, et al. Adjuvant Chemotherapy for Adult Soft Tissue Sarcomas of the Extremities and Girdles: Results of the Italian Randomized Cooperative Trial. Journal of Clinical Oncology, Vol 19, No 5 (March 1), 2001: pp 1238-1247. 6. Karen Antman, John Crowley, Stanley P. Balcerzak, et al. An Intergroup Phase III Randomized Study of Doxorubicin and Dacarbazine With or Without Ifosfamide and Mesnain Advanced Soft Tissue and Bone Sarcomas Journal of Clinical Oncology, Vol 11, No 7 (July), 1993: pp 1276-1285. 7. H. M. Pinedo,; V. H. C. BramvvelL, H. T. Mouridsen, et al. Cyvadic in Advanced Soft Tissue Sarcoma: A Randomized Study Comparing Two Schedules A Study of the EORTC Soft
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Tissue and Bone Sarcoma Group. Cancer 53:1825-1832, 1984. 8. Holcombe E. Grier, Mark D. Krailo, Nancy J. Tarbell et al. Addition of Ifosfamide and Etoposide to Standard Chemotherapy for Ewings Sarcoma and Primitive Neuroectodermal Tumor of Bone. N Engl J Med 348;694, 2003. 9. A. Kawai, H. Chuman, A. Makimoto, Y. Ito, et al. Ifosfamide etoposide chemotherapy in patients with advanced adult soft tissue sarcomas. Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 22, No 14S (July 15 Supplement), 2004: 9062 10. K. Scott Baker, James R. Anderson, Michael P. Link, Holcombe E. Grier, Stephen J. Qualman, Harold M. Maurer, John C. Breneman, Eugene S. Wiener, and William M. Crist. Benefit of Intensified Therapy for Patients With Local or Regional Embryonal Rhabdomyosarcoma: Results From the Intergroup Rhabdomyosarcoma Study IV. J Clin Oncol 18:2427-2434,2000. 11. I.Judson et al. Randomised Phase II Trial of pegylated liposomal doxorubicin versus doxorubicin in the treatment of advanced or metastatic soft tissuea sarcoma. European Journal of Cancer 2001; 37:870-877. 12. Jaap Verweij, Paolo G Casali, John Zalcberg et al. Progressionfree survival in gastrointestinal stromal tumours with highdose imatinib: randomised trial. Lancet 2004; 364: 1127134. 13. George D Demetri, Allan T van Oosterom, Christopher R Garrett, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 2006; 368: 1329-38. 14. Talbot SM, et al. A phase II trial of temozolomide in patients with unresectable or metastatic soft tissue sarcoma. Cancer 2003;98:1942-6. 15. Merimsky O, et al. Gemcitabine in soft tissue or bone sarcoma resistant to standard chemotherapy: a phase II study Cancer Chemother Pharmacol 2000;45:177-81 16. Fata F, et al. Paclitaxel in the treatment of patients with angiosarcoma of the scalp or face. Cancer 1999;86:2034-7.
205
Sarcoma de Kaposi
Daunorrubicina lipossomal Daunorrubicina lipossomal: 40 mg/m IV D1 a cada 14 dias Ref. (1) Doxorrubicina lipossomal peguilada Doxorrubicina lipossomal peguilada: 20 mg/m IV D1 a cada 21 dias Ref. (2) Paclitaxel Paclitaxel: 135 mg/m IV durante 3 horas D1 a cada 21 dias Ref. (3) OU Paclitaxel: 100 mg/m IV durante 3 horas D1 a cada 14 dias ABV Doxorrubicina: 20 mg/m IV Bleomicina: 10 mg/m IV Vincristina: 1 mg IV Ref. (4)
D1 D1 D1
a cada 14 dias
1. Gill PS, et al. Randomizes phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS- related Kaposis sarcoma. J Clin Oncol 1996;14:2353-2364.
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2. Northfelt DW, et al. Efficacy of pegylated-liposomal doxorubicin in the treatment of AIDS relates Kaposis sarcoma after failure of standard chemotherapy. J Clin Oncol 1997;15:653-659. 3. Gill PS, et al. Paclitaxel is safe and effective in the treatment of advanced AIDS-related Kaposis sarcoma. J Clin Oncol 1999;17:1876-1880. Gill PS, et al. Multicenter trial of low-dose paclitaxel in patients with advanced AIDS-related Kaposis sarcoma. Cancer 2002;95:147-154. 4. Northfelt DW, et al. J Clin Oncol 1998;16:2445-51.
207
Sarcomas sseos
Tratamento Neo-adjuvante
Doxorrubicina, Cisplatina e Methotrexate em altas doses (Pacientes com at 30 anos de idade) Fase pr-operatria Cisplatina: 60 mg/m2 IV D1 e D2 Semanas 0 e 5 2 Doxorrubicina: 25 mg/m IV contnuo D1 a D3 Semanas 0 e 5 Methotrexate*: 12 g/m2 (mximo 20 g) IV D1 Semanas 3, 4, 8 e 9 Leucovorin**: 10 mg (24 horas aps o Methotrexate) IV 6/6 horas D2 Semanas 3, 4,8 e 9 * Requer hidratao do paciente e alcalinizao da urina com infuso de bicarbonato de sdio; ** O cido foinico mantido at o nvel srico de Methotrexate atingir concentrao menor que 100 nmol/L. Fase ps-operatria Cisplatina: 60 mg/m2 IV D1 e D2 Semanas 12 e 17 Doxorrubicina: 25 mg/m2 IV contnuo D1 a 03 Semanas 12,17, 22 e 27 Methotrexate*:12 g/m2 (mximo 20 g) IV D1 Semanas 15, 16, 20, 21, 25, 26, 30 e 31 Leucovorin: 10 mg (24 horas aps o Methotrexate) IV 6/6 horas D2 Semanas 15, 16, 20, 21, 25, 26, 30 e 31 * Se o paciente necessitar de um perodo de recuperao maior que 1 semana entre as doses das semanas 20 e 21 e das semanas 25 e 26, a segunda dose de Methotrexate poder ser suprimida, para no prejudicar a intensidade de dose da Doxorrubicina. Ref. (1)
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Doxorrubicina e Cisplatina Cisplatina: 100 mg/m2 IV 24 horas D1 2 Doxorrubicina: 25 mg/m IV D1 a D3 a cada 21 dias Ref. (2) Etoposide e Ifosfamida de induo, com regime complementar ps-operatrio Fase pr-operatria* Etoposide: 100 mg/m2 IV D1 a D5 2 Ifosfamida: 3500 mg/m IV 4 horas D1a D5 Mesna: 700 mg/m2 IV 4 horas D1 a D5 (combinada com a ifosfamida) Mesna: 700 mg/m2 IV 3 horas (aps a ifosfamida) D1 a D5 2 Mesna: 700 mg/m IV pulso Nas horas 3, 6 e 9 aps a Ifosfamida D1a D5 a cada 21 dias por 2 ciclos *A quimioterapia acima aplicada por dois ciclos (durao de 6 semanas), antes da cirurgia. Fase ps-operatria* Methotrexate*: 12 g/m2 (mximo 20 g) IV D1 Semanas 1, 2, 6, 7,11, 12, 16, 17, 30 e 31 Acido Folnico: 15 mg (24 horas aps o metotrexato) IV 6/6 horas (total 10 doses) D2 Semanas 1, 2, 6, 7,11,12,16, 17, 30 e 31 Cisplatina: 60 mg/m2 IV D1 e D2 Semanas 12 e17 2 Doxorrubicina: 37,5 mg/m IV D1e D2 Semanas 3, 13, 21, 27e32 Etoposide: 100 mg/m2 IV D1 a D5 Semanas 8, 18 e 24 Ifosfamida: 2400 mg/m2 IV 4 horas D1 a D5 Semanas 8, 18 e 24 Mesna: 480 mg/m2 IV 4 horas D1 a D5 (combinada com a ifosfamida) Semanas 8, 18 e 24 Mesna: 480 mg/m2 IV 3 horas (aps a ifosfamida) D1 a D5 Semanas 8, 18 e 24
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Mesna 480 mg/m2 IV pulso Nas horas 3, 6 e 9 aps a ifosfamida D1 a D5 Semanas 8, 18 e 24 *A quimioterapia de manuteno tem incio 1 ou 2 semanas aps a cirurgia. Ref. (3)
Sarcoma de Ewing
ICE Carboplatina: 400 mg/m2 IV D1 a D2 2 Etoposide: 100 mg/m IV D1 a D5 2 Ifosfamida*: 1800 mg/m IV D1 a D5 a cada 21 dias *Acompanhada de mesna para uroproteo. Ref. (4) Protocolo INT-0091 do Instituto Nacional de Cncer (NCI) Ciclo 1 Vincristina: 2 mg/m2 (mximo 2 mg)IV D1 2 Doxorrubicina: 75 mg/m IV D1 Ciclofosfamida**: 1200 mg/m2 IV D1 2 Dactinomicina***: 1,25 mg/m IV D1 a cada 42 dias Ciclo 2 Etoposide: 100 mg/m2 EV D1 a D5 2 Ifosfamida**: 1800 mg/m EV D1 a D5 a cada 42 dias *A quimioterapia aplicada a cada 21 dias, alternando o ciclo 1 com o ciclo 2, num total de 17 ciclos, equivalentes a 49 semanas; ** Acompanhada de mesna para uroproteo; ***A dactinomicina substitui a doxorrubicina quando a dose acumulada dessa droga atinge 375 mg/m2. Ref. (5)
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1. Meyers PA, et al. Osteosarcoma: A Randomized, Prospective Trial of the Addition of Ifosfamide and/or Muramyl Tripeptide to Cisplatin, Doxorubicin, and High-Dose Methotrexate. J Clin Oncol 2005;23:2004-11. 2. Bramwell VH, et al. A comparison of two short intensive adjuvant chemotherapy regimens in operable osteosarcoma of limbs in children and young adults: the first study of the European Osteosarcoma Intergroup. J Clin Oncol 1992;10:1579-91. 3. Goorin Am, et al. Phase II/III Trial of Etoposide and High-Dose Ifosfamide in Newly Diagnosed Metastatic Osteosarcoma: A Pediatric Oncology Group Trial. J Clin Oncol 2002;20:426-33. 4. Van Winkle P, et al. Ifosfamide, carboplatin, and etoposide (ICE) reinduction chemotherapy in a large cohort of children and adolescents with recurrent/refractory sarcoma: The Children's Cancer Group (CCG) experience. Pediatr Blood Cancer 2005;44:338-47. 5. Grier HE, et al. Addition of Ifosfamide and Etoposide to Standard Chemotherapy for Ewing's Sarcoma and Primitive Neuroectodermal Tumor of Bone. N Engl J Med 2003;348:694-701.
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Feocromocitoma
CVD Ciclofosfamida: 75 mg/m2 IV Vincristina: 1,4 mg/m2 IV Dacarbazina: 600 mg/m2 IV Ref. (1) D1 D1 D1-D2 a cada 21 dias
1. Huang Hui, Abraham Jame, Hung Elizabeth. Treatment of malignant pheochromocytoma/paraganglioma with cyclophosphamide, vincristine, and dacarbazine. Cancer. 2008; 113: 2020-2028.
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Classificao Internacional de Doenas CID Oncologia
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228
C00 C01 C02 C03 C04 C05 C06 C07 C08 C09 C10 C11 C12 C13 C14 C15 C16 C17 C18 C19 C20 C21 C22 C23 C24 C25 C26 C30 C31 C32 C33 C34 C37 C38 C39
Neopl. malig. do lbio Neopl. malig. da base da lngua Neopl. malig. outr partes e NE da lngua Neopl. malig. da gengiva Neopl. malig. do assoalho da boca Neopl. malig. do palato Neopl. malig. outr. partes e partes NE da boca Neopl. malig. da gland. partida Neopl. malig. outr. gland. saliv. maiores e NE Neopl. malig. da amgdala Neopl. malig. da orofaringe Neopl. malig. da nasofaringe Neopl. malig. do seio piriforme Neopl. malig. da hipofaringe Neopl. malig. out. loc. mal def. labio cav. oral far. Neopl. malig. do esfago Neopl. malig. do estmago Neopl. malig. do intestino delgado Neopl. malig. do clon Neopl. malig. da juno retossigmide Neopl. malig. do reto Neopl. malig. do nus e do canal anal Neopl. malig. fgado vias biliares intra-hepat Neopl. malig. da vescula biliar Neopl. malig. outras partes e NE vias biliares Neopl malig do pncreas Neopl. malig .outr. mal def. aparelho digestivo Neopl. malig. cavidade nasal e do ouvido mdio Neopl. malig. dos seios da face Neopl. malig. da laringe Neopl. malig. da traquia Neopl. malig. dos bronquos e dos pulmes Neopl. malig. do timo Neopl .malig. do corao mediastino e pleura Neop. malig. out. loc. mal def. ap. resp. org. intrat.
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C40 C41 C43 C44 C45 C46 C47 C48 C49 C50 C51 C52 C53 C54 C55 C56 C57 C58 C60 C61 C62 C63 C64 C65 C66 C67 C68 C69 C70 C71 C72 C73 C74 C75 C76
Neopl. malig. ossos/cartilag. artic. membros Neopl. malig. ossos/cartil. artic. outr. loc. e NE Melanoma malig. da pele Outr. neopl. malig. da pele Mesotelioma Sarcoma de Kaposi Neopl. malig. nervos perif. e sist. nerv. autnom. Neopl. malig. tec. moles retro- e peritonio Neopl. malig. tec. conjuntivo e outr. tec. moles Neopl. malig. da mama Neopl. malig. da vulva Neopl. malig. da vagina Neopl. malig. do colo do tero Neopl. malig. do corpo do tero Neopl. malig. do tero poro NE Neopl. malig. do ovrio Neopl. malig. outr. org. genitais femin. e NE Neopl. malig. da placenta Neopl. malig. do pnis Neopl. malig. da prstata Neopl. malig. dos testculos Neopl. malig. outr. org. genit. masc. e NE Neopl. malig. do rim exceto pelve renal Neopl. malig. da pelve renal Neopl. malig. dos ureteres Neopl. malig. da bexiga Neopl. malig. de outr. orgos urinrios e NE Neopl. malig. do olho e anexos Neopl. malig. das meninges Neopl. malig. do encfalo Neopl. mal. med. esp. nerv. cran. out. sist. nerv. cen. Neopl. malig. da gland. tireide Neopl. malig. da gland. supra-renal Neopl. malig. outr. gland. endcrinas estr. relac. Neopl. malig. outr. localiz. e mal definidas
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C77 C78 C79 C80 C81 C82 C83 C84 C85 C88 C90 C91 C92 C93 C94 C95 C96 C97
Neopl. malig. secund. e NE gangl. linfticos Neopl. malig. secund. org. respirat. e digestivos Neopl. malig. secund. de outr. localiz. Neopl. malig. s/especificao de localiz. Doenc. de Hodgkin Linfoma no-Hodgkin folicular Linfoma no-Hodgkin difuso Linfomas de clulas T cutneas e perifricas Linfoma no-Hodgkin de outr. tipos e tipo NE Doenc. imunoproliferativas malignas Mieloma mlt. e neopl. malig. de plasmcitos Leucemia linfide Leucemia mielide Leucemia monoctica Outr. leucemias de clulas de tipo espec. Leucemia de tipo celular NE Outr. neopl. mal. e NE tec. linf. hematop. e corr. Neopl. malig. de localiz. mult. independentes
231
Notas
232
Correo de Dose para Pacientes em (1) Hemodilise
221
222
DROGA
NECESSIDADE DE AJUSTE EM HEMODILISE No Sem informao Sim Sim Sim Sem informao No No Sim No Sem informao Sem informao Sem informao No Sim
Adaptado de Janus N. et al (1)
5-Fluorouracil Capecitabina Carboplatina Cisplatina Ciclofosfamida Docetaxel Doxorrubicina Epirrubicina Etoposide Gencitabina Irinotecano Methotrexate Oxaliplatina Paclitaxel Vinorelbina
223
DROGA
VIA ELIMINAO
ADMINISTRAR
5FU Capecitabina Carboplatina Cisplatina Ciclofosfamida Docetaxel Doxorrubicina Epirrubicina Etoposide Gencitabina Irinotecano Methotrexate Oxaliplatina Paclitaxel Vinorelbina
Respiratria Aps HD Urinria Aps HD Urinria Urinria Urinria Fezes Fezes Fezes Fezes Urinria Fezes Urinria Urinria Fezes Fezes Aps HD Aps HD Aps HD Antes ou Aps HD Aps HD Aps HD Antes ou Aps HD 6 a 12h antes da HD Aps HD Aps HD Aps HD Antes ou Aps HD Aps HD
DOSE GRAU RECOMEN- DE DADA RECOMENDAO Usual C Sem informao Dose=AUC B x (25+0) Reduo de B 50 a 75% Reduo B de 25% 65mg/m2 C Usual Usual Reduo de 50% Usual Sem informao Reduo de 75% Reduo de 30% Usual Reduo de 20 a 30% C C B B C C B C
HD: hemodilise. Adaptado de Janus N. et al (1)
224
PROTOCOLO
DROGAS AJUSTE DE DOSE Irinotecano, Leucovorin, 5FU Sim
DOSES RECOMENDADAS Irinotecano 50mg/m2 semanal, Leucovorin 10mg/m2,semanal,5FU 400mg/m2 semanal Oxaliplatina 32mg/m2,5FU 240mg/m2 pulso e 400mg/m2 infusional Irinotecano 120mg/m2 Ciclofosfamida 375mg/m2, Epirrubicina 100mg/m2,5FU 500mg/m2 Carboplatina AUC x(25+0), Docetaxel 65mg/m2 Cisplatina 25mg/m2, Gencitabina 1000mg/m2 Cisplatina 25mg/m2, Docetaxel 65mg/m2 Cisplatina 25mg/m2, Paclitaxel 135mg/m2 em 24 horas ou 175mg/m2 em 3 horas
IFL (Saltz)
FOLFOX4
Oxaliplatina, 5FU
Sim
FOLFIRI
Irinotecano, 5FU Ciclofosfamida, FEC100 Epirrubicina, 5FU Carboplatina+ Carboplatina, Docetaxel Docetaxel Cisplatina+ Gencitabina Cisplatina+ Docetaxel Cisplatina+ Gencitabina Cisplatina, Gencitabina Cisplatina, Docetaxel Cisplatina, Gencitabina
Sim
Sim
Sim
Sim Sim
Sim
Adaptado de Janus Net al (1) 1. Janus N, Thariat J et al. Proposal for dosage adjustment and timing of chemotherapy in hemodialyzed patients. Ann Oncol. 2010, 21, 1395-1403.
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Sociedade Brasileira de Cancerologia
2011
Organizao Dra. Aline Lauda Freitas Chaves Dra. Letcia Carvalho Neuenschwander Reviso Dr. Amndio Soares Fernandes Jnior Dr. Enaldo Melo de Lima Dr. Jos Luiz Miranda Guimares Srta. Paula Palmeira - Bibliotecria da SBOC
Editorial
Caros Oncologistas Clnicos Associados da SBOC e da SBC; A SBOC, em conjunto com a SBC, elaborou esse compndio com os principais protocolos de tumores onco-hematolgicos, para facilitar a consulta no dia a dia dos esquemas de dose e frequncia de tratamento. A confeco e compilao dos dados da literatura mdica coube s Dras. Aline Lauda Freitas Chaves e Letcia Carvalho Neuenschwander e, aps a elaborao do guia, foram realizadas diversas correes no contedo e diagramao, a fim de evitar informaes incorretas, que pudessem gerar erros de prescrio e danos aos pacientes. Um esforo considervel foi dispendido para evitar erros e garantir a acurcia dos regimes apresentados. Esse guia prtico incorpora os esquemas mais amplamente utilizados, tanto de monoterapia, como poliquimioterapia, alm de hormonioterapia, bioterapia, anticorpos monoclonais e pequenas molculas, que so utilizados na prtica oncolgica do dia a dia para tratamento de tumores slidos e das neoplasias hematolgicas. Ambas as entidades pretendem atualizar, anualmente esse trabalho, tendo em vista a rpida evoluo da nossa especialidade e entendem esse trabalho como uma continuidade da prestao de servio aos associados, com a incorporao de novos esquemas e programas de tratamento. Cordialmente,
Dr. Enaldo Melo de Lima

Presidente da SBOC
Dr. Roberto Porto Fonseca

Presidente da SBC
Apresentao
Dentro da proposta das atuais diretorias da SBOC e SBC, temos uma maior aproximao entre essas entidades e seus associados, principalmente no que tange a facilitar a vida do Oncologista Clnico no Brasil. Foi dentro desta linha que surgiu este guia rpido de protocolos, com informaes teis para o dia a dia da prtica do oncologista. Para mont-lo fizemos inicialmente a pergunta: O que o oncologista tem que ter em mos no momento de sua prtica clnica junto ao paciente? Seu intuito, portanto, ser um guia de consulta prtico, rpido e acessvel. importante ressaltar que no substitui o raciocnio clnico e nem pode ser considerado um manual de condutas de tratamento. Justamente por isso no foram separados subcaptulos de tratamento adjuvante, neoadjuvante, paliativo. Todos os dados aqui apresentados foram compilados na literatura mdica disponvel, com referncias citadas no final de cada captulo. Esperamos que seja til a todos.
Dra. Aline Lauda Freitas Chaves Dra. Letcia Carvalho Neuenschwander

Belo Horizonte - MG Agosto/2011
Escala de Performance
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214
ECOG 0 a 4
GRAU 0 NVEL DE ATIVIDADE Completamente ativo, capaz de realizar todas as atividades tal como antes da doena, sem restries (Karnofsky 90-100%). Restrio de atividades fisicamente estenuantes, mas deambulando e capaz de resolver tarefas leves ou sedentrias, por exemplo, trabalhos domsticos leves, servios de escritrio (Karnofsky 70-80%). Deambulando e capaz de cuidar de si prprio mas incapaz de realizar qualquer trabalho; de p e ativo mais de 50% das horas em que passa acordado (Karnofsky 50-60%). Limitao da capacidade de se autocuidar, confinado ao leito ou a uma poltrona durante mais de 50% do perodo em que permanece acordado (Karnofsky 30-40%). Completamente incapacitado; no consegue executar qualquer autocuidado; totalmente confinado ao leito ou poltrona (Karnofsky 1020%).
Oken, MM, Creech, RH, Tormey, DC, Horton, J. Davis, TE, McFadden, ET, Carbone, PP: Am J Clin Oncol 5:649-655, 1982.
215
Notas
216
Frmulas teis em Oncologia
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218
Determinao do Clearance de Creatinina

Frmula de Cockcroft-Gault (Cockcroft, DW, Gault, MH. Nephron 1976; 16: 3134): Clearance de creatinina (ml/min) = Peso (Kg) x (140 idade) 72 x creatinina srica (mg/dl) Para mulheres multiplicar o resultado por 0,85.
Determinao da rea sobre a curva (AUC)

Calvert, H, et al. J Clin Oncol 1989;7:17481756 Dose de Carboplatina (mg) = (25 + Clearance ml/min) x AUC AUC mais usadas: 5 a 7
219
Sites teis em Oncologia
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234
www.sboc.org.br www.sbcancer.org.br www.inca.gov.br www.asco.org www.nccn.org www.cancer.gov www.esmo.org www.pubmed.com www.bvs.org.br
235
Notas
236
Notas
237
Notas
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Notas
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Notas
Projeto Grfico e Diagramao Communicatio Design www.communicatio.com.br
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Sumrio
Protocolos de Tratamento
Tumor de Stio Primrio Desconhecido Tumores do Sistema Nervoso Central Tumores Neuroendcrinos Cncer Anal Cncer Colo-retal Cncer de Intestino Delgado Cncer de Esfago Cncer Gstrico e Juno Gastroesofgica Tumor do Estroma Gastrointestinal (GIST) Hepatocarcinoma Cncer de Vias Biliares Cncer de Pncreas Cncer de Cabea e Pescoo Linfoepitelioma Nasofaringe Cncer de Tireide Cncer de Glndula Salivar Cncer de Bexiga Cncer Renal Cncer de Prstata Cncer de Testculo Cncer de Pnis Cncer de Endomtrio Cncer de Colo Uterino Cncer de Mama Metstases sseas e/ou Hipercalcemia Maligna Cncer de Ovrio (Epitelial) Doena Trofoblstica Gestacional Cncer de Vulva Cncer de Pulmo No Pequenas Clulas Cncer de Pulmo de Pequenas Clulas
.07
.09 .15 .20 .24 .26 .39 .41 .44 .50 .51 .53 .56 .61 .65 .72 .73 .75 .80 .83 .88 .92 .93 .98 .101 .121 .122 .128 .130 .131 .140
Mesotelioma Timoma Melanoma Maligno Linfoma de Hodgkin Linfoma No-Hodgkin Linfoma de Grandes Clulas B Linfoma de Clulas do Manto Linfoma Primrio do Sistema Nervoso Central Mieloma Mltiplo Sndrome Mielodisplsica Macroglobulinemia de Waldestrn Leucemia de Clulas Cabeludas (Tricoleucemia) Leucemias Agudas Leucemia Mielide Crnica Leucemia Linftica Crnica Sarcomas de Partes Moles Sarcoma de Kaposi Sarcomas sseos Feocromocitoma
.144 .147 .149 .154 .160 .171 .172 .176 .179 .185 .187 .188 .190 .194 .195 .200 .206 .208 .212
Escala de Performance Frmulas teis em Oncologia

Determinao do Clearance de Creatinina Determinao da rea sobre a curva (AUC) Clculo da Superfcie Corporal
.213 .217
.219 .219 .220
Correo de Dose para Pacientes em Hemodilise Classificao Internacional de Doenas CID Oncologia Sites teis em Oncologia
.221 .227 .233

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Guia miolo correo_Manual Conflito.

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Tumor de Stio Primrio Desconhecido

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Guia Prtico para o Oncologista Clnico

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GCV Cisplatina: 35mg/m2 IV D1 e D8 Gencitabina: 1000mg/m2 IV D1 e D8 Vinorelbina: 25mg/m2 IV D1 e D8 a cada 21 dias

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Tumores do Sistema Nervoso Central

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Irinotecano Irinotecano: 350 mg/m2 IV em 90 min D1 a cada 3 semanas

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Guia Prtico para o Oncologista Clnico

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Guia Prtico para o Oncologista Clnico

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Guia Prtico para o Oncologista Clnico

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Guia Prtico para o Oncologista Clnico

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Guia Prtico para o Oncologista Clnico

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Guia Prtico para o Oncologista Clnico

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Guia Prtico para o Oncologista Clnico

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Guia Prtico para o Oncologista Clnico

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Guia Prtico para o Oncologista Clnico

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Guia Prtico para o Oncologista Clnico

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Guia Prtico para o Oncologista Clnico

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Capecitabina Capecitabina: 1.250 mg/m2 VO BID D114 a cada 21 dias

Ref. (36, 37)

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Cncer de Intestino Delgado

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