DASAR – DASAR KEMOTERAPI

PADA PENDERITA KANKER

PELATIHAN SINGKAT TATALAKSANA KEMOTERAPI

PADA PENDERITA KANKER
BAGI TENAGA PARAMEDIS / PERAWAT RUMAH SAKIT
SANGLAH DENPASAR, 15 APRIL 2006
 PENDAHULUAN
 MODALITAS TERAPI KANKER:

BEDAH
RADIAOTERAPI
KEMOTERAPI
TERAPI HORMONAL

TERAPI GEN
TERAPI IMUNOLOGI
 Pedahuluan
KEMOTERAPI

BAGIAN INTEGRAL PENANGANAN KANKER.

BAHAN KIMIA YG DAPAT MENGHAMBAT PERTUMBUHAN SEL
KANKER.
OBAT KERAS
TATALAKSANA KHUSUS

PERLU PENGETAHUAN, KETERAMPILAN YANG MEMADAI

 TUJUAN PEMBERIAN KEMOTERAPI
Mencapai kesembuhan (kuratif)
Mempepanjang masa bebas penyakit
(DFS).
Memperpanjang lama hidup (Survival)
Memperbaiki kualitas hidup (QoL)

SEBAGAI: Adjuvant
Neoadjuvant
Terapi utama
Radiosensitizer
 PRINSIP DASAR

 ASPEK ONKOLOGI
 ASPEK PENDERITA DAN KELUARGA
 HASIL PENGOBATAN DAN EFEK SAMPING
 ASPEK ONKOLOGI
 Diagnosis kanker:
Klinis, Imaging, Patologi. Marker
Biologi.
 Stadium kanker
 Performance status (Karnofski,
ECOG,WHO). faktor risiko
 Aspek penderita dan keluaga
 INFORMASI MENGENAI:
Indikasi
Jenis, cara, siklus, lama pemberian obat
Efek samping
Informed consent
 Hasil terapi dan efek samping
 Hasil terapi sesuai dengan tujuan
pengobatan
 Efek samping:
diagnosis
penanganan
KEMOTERAPI YANG BAIK
 EFEKTIF
 AMAN
 SPESIFIK
 SELEKTIF
 CARA KERJA KEMOTERAPI
 BEKERJA PADA SEL YANG SANGAT AKTIF
 DOSIS MAKSIMUM YANG DITOLERANSI
 Tingkat seluler:
Sel proliferasi
Siklus sel
Apoptosis

 Fase spesifik atau non spesifik

 Cara pemberian :IV, Oral, instilasi, perfusi
 Terapi tunggal atau kombinasi
 DNA replication
P33 cdc2Cyclin A

S
Start/Restriction point
G1 Control
P33 cdc7, p34 cdc4, p33cdc6
MAP kinase
Cyclin E & D
P53
Synthesis enzyme for DNA
G1 G2

MAP kinase G2 control

P34cdc2 cyclin A& B
M

Mitosis/Miosis
P34 cdc2 Cyclin B

Taxan : microtubulin, m’blok mitosis dg m’aktivasi p34 cdc2

Doxo : merangsang p53
 Vinblastine
Vincristine
5 FU Colchicine
Phleomycin
Griseofulvin
Bleomycin
Cyclophosphamide
0,5-1h
Actinomycin 0.5-1h Differentiation

G2 M Hydrocortisone
2-10h Chalones
Purin antagonis
Hydroxy urea
Actinomycin D
S G1
Cyclophosphamide Mytomycin
6-20h 18-30h
6-Marcaptopurine
Doxorubicin
6-Thioguanine

5 Fudr .5FU, Ara C. 5 Fudr

Mitomycin,Doxorubicin ara C
Thioguanine 6-Hydroxyurea
5 FU
METHOTREXATE
Alkylating agent, Antimetabolit,Mitotic inhibitor,
Antibiotic
 Number of No response Early recurrence Late recurrence
Tumor cell 1012
(1kg)

109 Tumor detectable

(1 g) (clinically)

106 Long-term Remission

(1 mg) Not palpable

Tumor invisible
Immune resistance
(Remission) 103 of host
(1 úg)
(humoral&cellular)

Induction Consolidation Maintenance Cure

CANCER TREATMENT OUTCOME

1.Objective Response Evaluation

2.Subjective Response Evaluation
(3). Survival
 OBJECTIVE RESPONSE EVALUATIONS

1. TUMOR SIZE :
- Complete remission (CR)
- Partial remission (PR)
- No Changes (Stable Disease = St D)
- Progressive Disease (PD)
2. Marker Tumour :
- CEA, CA15-3, MCA  Breast Ca
- CEA, CA19-9  Pancreas Ca, Colorectal Ca
- HCG  Chorio Ca
- PSA  Prostat Ca

3. Objective-Qualitative :
- Change of Clinical sign : Brain Ca-neurology sign
SUBJECTIVE RESPONSE EVALUATION

Performance status : Karnofsky / ECOG

Palliative

CURATIVE : caution of safety and side effects

 SIDE EFFECT MONITORING

DIAGNOSE of Side Effect

PHARMACOLOGY
When Side effect become: NADIR point (degree of SE)
Onset of SE, Specificity of organ target

MANAGEMENT of Side Effect

Anticipation & Prevention
Dose related side effect monitoring
Early treatment of side effect
1. Onset of SE :
- Immediately ( < 1 Hour post Chemotx)  Anaphylaxsis
- early (1- 48 hours )  Nausea-Vomiting profuse
- delayed (2 days -2 months )  leucopenia
- Late (after 2 months )  myopathy, neuropathy

2.Organ Target : Haematologic, Skin, Cardiovascular,

Respiratory, Gastrointestinal, CNS.

3.Level/degree of SE (IUCC,WHO, ECOG) :

- grade 0-2 : tolerable ( safety enough )
- grade 3 (severe) : must be alert (Yellow light), need treatment ±
- grade 4 (life threatening) : Hazard, early and adequate treatment
PROFILE EPISODE of FEBRIL NEUTROPENI

1 6 11 16 21 26
nadir Chemotherapy day

Chemotherapy day
 FEBRILE NEUTROPENIA
CRITERIA :
• NEUTROPENIA :
absolute count of neutrophill in circulating blood < 2000 cells/mm3
• FEVER :
body temperature > 38.50C in 3 x measurement per 24 hours

DEGREE OF NEUTROPENIA

• Mild : 2000 – 1000 cells/mm3

• Moderate : 1000 – 500 cells/mm3
• Severe : < 500 cells/mm3
TREATMENT of FEBRIL NEUTROPENI

Empiric antibacterial

nadir Chemotherapy day

Empiric antibacterial
G-CSF
Sterile room

Chemotherapy day
Hiperpigmentation (Fluorouracil )
 Management Side Effect
1. ANTIDOTUM to specific agent :
- Antidotum of MTX : Calcium leucovorin, Ca Lefofolinat
- Cardiomyopathy prophylaxis – Doxorubicin > 450 mg/m2
* Dexrazosane 10 mg – Doxorubicin 1 mg

2. Dose modification :
- Toxicity grade 3 and 4 : decrease dose 25% - 50%

3. Supportive Drugs :
- Haemopoetic GF : G-CSF, GM-SF, IL-3, Epo
- Component Blood transfuse
- Selective antibiotic

4. Sterile Room technology

Three types of CINV:
 Acute nausea vomiting (12-24h)
 Delayed nausea vomiting (up to 5 days)
 Anticipatory nausea vomiting (result from
patient’s expectation (anticipation) of NV.
Risk factors for CINV:
 Patients risk factors:
Age
Gender
History of NV
History of alcohol use.
 Drug risk factors (see table)
 Procedural risk factors (RINV).
Emetogenic potential of antineoplastic agents
High risk Moderate risk Low risk
Altretamine Docetaxel Bleomycin
Carboplatin Etoposide Busulfan
Carmustine Fluorouracil Chlorambucil
Cisplatin Gemcitabine Fludarabine
Cyclophosphamide Mitomycin Hydroxyurea
(high-dose) Paclitaxel Melphalan
Cytarabine Vinblastine
Dacarbazine Vincristine
Doxorubicin Vinorelbine
Epirubicin
Ifosfamide
Mitoxantrone
Streptozocin

Markman M. CCJM 2002;69(8):609-617.

Emetogenic Potential of Single Chemotherapy Agents
Level Frequency of Chemotherapeutic
Emesis (%) Agents
5 > 90 Carmustine > 250 mg/m2
Cisplatin >=50 mg/m2
Cyclophosphamide >1,500 mg/m2
Dacarbazine
Mechlorethamine
Streptozocin

4 60 – 90 Carboplatin
Carmustine <=250 mg/m2
Cisplatin <50 mg/m2
Cyclophosphamide >750 mg/m2 <=1,500 mg/m2
Cytarabine >1 g/m2
Doxorubicin >60 mg/m2
Methotrexate >1,000 mg/m2
Procarbazine (oral)

3 30 – 60 Cyclophosphamide >=750 mg/m2

Cyclophosphamide (oral)
Doxorubicin 20-60 mg/m2
Epirubicin <=90 mg/m2
Hexamethylmelamine (Oral)
Idarubicin
Ifosfamide
Methotrexate 250-1,000 mg/m2
Mitoxantrone <15 mg/m2

2 10 – 30 Docetaxel
Etoposide
5-Fluorouracil >1,000 mg/m2
Gemcitabine
Methotrexate >50 mg/m2 to <250 mg/m2
Mitomycin
Paclitaxel

1 < 10 Bleomycin
Busulfan
Chlorambucil (oral)
2-Chlorodexyadenosine
Fludarabine
Hydroxyurea
Methotrexate <=50 mg/m2
L-phenylalanine mustard (oral)
Thioguanine (oral)
Vinblastine
Vincristine
Vinorelbine
Hesketh PJ, Kris MG, Grunberg SM, et al. J Clin Oncol. 1997;15:103-109
 The neuronal pathway of CINV
 Vomiting center in the medulla (lateral
reticular formation)
 Chemoreceptor Trigger Zone (CTZ) area
prostrema 4th ventricle.
 Neurotransmitters: dopamin, serotonin,
neurokinin and their receptors.
 Nuroreceptors in Enterochromaffin cell GI
tract.
Emetic mechanism due to chemotherapy and radiotherapy

Chemotherapy
/Radiotherapy
Opiat /stimulus

Enterochromaffin sel
Emetic Center
r.5-HT3B

(seretonin)
r.5-HT3A
CTZ r. 3A

Vagal afferent
nerve terminal
Gut-wall
Emetogenic
stimulus
 Complication of CINV
 Dehydration
 Electrolyte imbalance
 Aspiration pneumonia
 Very distressing for patients  choosing
discontinue potentially curative therapy.
 Economic burden
 Treatment of CINV
 Preventing CINV is more effective than
treating it
 Anti emetic drugs:
Serotonin-receptor antagonist (5-HT3
receptor antagonist).
Corticosteroid
Others
corticosteroids potentiate seretonin-
receptor antagonist.
Serotonin-receptor antagonists
DRUG DOSAGE

Dolasetron 100 mg IV (single dose)

100 mg orally (single dose)
Granisetron 1-2 mg IV (single dose)
1 or 2 mg orally (single dose)
Ondansetron 8 mg IV (single dose)
16-24 mg orally (single dose)
or 8 mg orally twice daily
Others (Tropisetron, Itasetron)
Other agents used to prevent and treat
Chemotherapy-induced emesis

DRUG DOSAGE

Dexamethasone 20 mg IV over 5 minutes (single dose)

20 mg orally (single dose)
Lorazepam 0.5-2 mg IV every 4-6 hours as needed
0.5-2 mg orally every 6 hours as needed
Metoclopramide 2-3 mg/kg IV every 2 hours
2-3 mg/kg orally every 2-3 hours
Haloperidol 1-2 mg IV every 4-6 hours
1-2 mg orally every 4-6 hours
Dronabinol 5 mg/m2 orally every 4 hours
Prochlorperazine 10-20 mg IV every 3-4 hours
5-10 mg orally every 4-6 hours
25 mg suppository every 6 hours
Regimens to prevent delayed
chemotherapy-induced emesis
DRUG DOSAGE

Metoclopramide 30-40 mg orally twice a day

plus dexamethasone 8 mg orally twice a day
(both for 3 days)
Ondansetron 8 mg orally twice a day
plus dexamethasone 8 mg orally twice a day
(both for 3 days)
Tepat indikasi : kemoterapi tepat dipilih berdasar titik
tangkap kerjanya berdasar patogenesis kanker  sehingga
dapat tercapai tujuan :
1.kuratif
2.mencapai bebas penyakit (DFS) yang lebih lama
3.neoadjuvant (Mikrometastasis,mengecilkan volume tumor
preoperasi-down staging)
4.mempertahankan atau meningkatkan quality of life
(terapi paliatif)
Tepat jenis obat : sebaiknya lebih spesifik, selektif, mem-
punyai Response rate tinggi, established,
dan dapat dijangkau oleh penderita

Tepat dosis obat : sesuai Maximum Tolerated Dose

( Risk group )
Tepat cara pemberian obat : oral, IV, bolus, infusion dsb
yang penting : penderita nyaman , tidak takut dan
dengan kesadaran sendiri ingin melanjutkan kemoterapi

Tepat monitoring efek obat :

- penilaian hasil / respons terapi
- kemampuan hidup (quality of life) dan
- efek samping obat
 TERIMAKASIH
SEMOGA BERMANFAAT