KEMOTERAPI PADA PASIEN

KANKER
APA ITU KEMOTERAPI
SEL KANKER VS SEL NORMAL
Modalitas Pengobatan Kanker
Operasi
Lokal
Radiasi

Terapi Kanker
Kemoterapi

Sistemik Hormon Terapi

Immunoterapi
Tujuan Pemberian Kemoterapi

Ajuvan

Kuratif

Tujuan Neo Ajuvan

Pemberian
Kemoterapi

Paliatif Prolong Life

Tujuan Pemberian Kemoterapi
 Kemoterapi Adjuvant :
 Diberikan bersama terapi yang lain ( bedah & radiasi )
 Untuk menghilangkan residu mikro metastasis yang menyebabkan sel kanker tumbuh
kembali

 Kemoterapi Neoadjuvant :
 Diberikan sebelum terapi lain (pembedahan), untuk mengurangi masa tumor → proses
pembedahan tdk berbahaya
 Dapat menghilangkan mikro metastasis

 Kemoterapi Paliatif
 Mengurangi ukuran masa tumor
 Mengatasi simptomatik : obstruksi, nyeri
Tujuan Pemberian Kemoterapi
• Induksi Kemoterapi : Terapi awal yang diberikan dengan tujuan
untuk mereduksi sel kanker semaksimal mungkin. Diharapkan
terjadi complete remission dari Induksi Kemoterapi ini.
• Konsolidasi / Intensifikasi : kemoterapi yang diberikan setelah
remisi, untuk memperpanjang disease free survival
• Konsolidasi terapi biasanya menggunakan obat yang sama dengan
induksi atau obat yang lain untuk intensifikasi terapi konsolidasi
tetapi tidak menimbulkan cross resistance dengan induksi
kemoterapi..
Tujuan Pemberian Kemoterapi
• Maintenance chemotherapy : Perpanjangan
terapi dengan dosis rendah untuk
memperpanjang durasi dari remisi dan mencapai
kesembuhan.
• Salvage Therapy : Terapi yang diberikan setelah
gagal terhadap regimen therapy yang lain.
Tujuan dari salvage therapy untuk palliative
Pemilihan Terapi
• Usia
Kondisi
• Comorbid
Pasien disease

Jenis • Jenis kanker

Penyakit • Lokasi organ

• Stadium
Stadium
• Derajat
Penyakit Keganasan
MEKANISME KERJA OBAT KANKER BERDASAR
SIKLUS SEL
MEKANISME KERJA OBAT KANKER PADA DNA
PENGGOLONGAN OBAT SITOSTATIKA
 Golongan Kemoterapi

Agen Pengalkil Anti-Metabolit

Vinca Alkaloid
Cyclophosphamide Methotrexate (MTX)
Vincristine
Ifosfamide 5-Fluorouracil (5-FU)
Vinorelbine
Chlorambucil Cytarabine
Vinblastine
Dacarbazine Gemcitabine

Antibiotik
Taxane Platinum
Bleomycin
Paclitaxel Cisplatin
Doxorubicin
Docetaxel Carboplatin
Epirubicin
Cabazitaxel Oxaliplatin
Mitomycin

Hormonal
Analog
Tamoxifen
Camptothecin
Letrozole
Topotecan
Anastrozole
Irinotecan
Exemestane
ALKYLATING AGENT
 ALKYLATING AGENT

KLASIFIKASI NAMA OBAT

• Mechlorethamine
• Cyclophosphamide
Nitrogen Mustards • Ifosfamide
• Melphalan
• Chlorambucil
• Altretamine
Ethylenamine and methylenamine derivatives
• thiotepa
Alkyl sulfonates Busulfan
• Carmustine
Nitrosoureas
• Lomustine
• Dacarbazine
Triazenes • Procarbazine
• Temozolomide
• Cisplatin
The platinum-containing antineoplastic
• Carboplatin
agents
• Oxaliplatin
ANTIMETABOLIT
 ANTIMETABOLIT
KLASIFIKASI NAMA OBAT
Methotrexate
Pemetrexed
Antifolates
Pralatrexate
Trimetrexate
Azathioprine
Cladribine
Purine Analogues Fludarabine
Mercaptopurine
Thioguanine
Azacitidine
Capecitabine
Cytarabine
Decitabine
Pyrimidine Analogues
Floxuridine
Fluorouracil
Gemcitabine
Trifluridine/Tipracil
ANTITUMOR ANTIBIOTIK
PLANTA ALKALOID
Golongan Obat Nama Obat
•Bleomycin, •Idarubicin,
•Dactinomycin, •Mitomycin,
Antitumour
•Daunorubicin, •Mitoxantrone,
Antibiotics
•Doxorubicin, •Plicamycin,
•Epirubicin, •Valrubicin
•Vinblastine,
•Vincristine,
Plant alkaloid •Vinorelbine
•Vindesin Sulfat
•Etoposide
•Mitotane, •Asparaginase
•Omacetaxine, (Pegaspargase),
•Pomalidomide, •Bexarotene,
Miscellaneous •Tagraxofusp, •Eribulin,
agent •Telotristat, •Everolimus,
•Temsirolimus, •Hydroxyurea,
•Thalidomide, •Ixabepilone,
•Venetoclax •Lenalidomide,
•Paclitaxel
Taxane
•Docetaxel
 Protein (tyrosine kinase)
inhibitors
No. Zat aktif Indikasi Efek Samping
1 Afatinib dimaleate Treatment of locally Diarrhea, stomatitis,
advanced or metastatic nausea, vomiting, rash,
non-squamous NSCLC paronychia,
2 Crizotinib Treatment of ALK Vision disorders, nausea,
positive advance NSCLC diarrhea, vomiting, edema,
constipation, elevated
transaminase, fatigue,
decreased appetite,
dizziness, neuropathy
 Protein (tyrosine kinase)
inhibitors
No. Zat aktif Indikasi Efek Samping
3 Axitinib Tratment of renal diarrhoea, hypertension,
cell carcinoma fatigue, decreased appetite,
nausea, weight decreased,
dysphonia, palmar-plantar
erythrodysaesthesia (hand-foot)
syndrome, haemorrhage,
hypothyroidism, vomiting,
proteinuria, cough, and
constipation.
 Protein (tyrosine kinase)
inhibitors
No. Zat aktif Indikasi Efek Samping
4 Erlotinib Treatmet of locally Rash, diarrhea, fatigue,
advance or metastatic keratitis, conjunctivitis,
NSCLC with EGFR epistaxis, gastrointestinal
activating mutations bleeding, aliopecia, dry
skin, paronychia,
Treatment of locally Folliculitis, Acne/
advance , unresectable Dermatitis acneiform, Skin
or metastatic fissures
pancreatic cancer
 Protein (tyrosine kinase)
inhibitors
No. Zat aktif Indikasi Efek Samping
5 Gefinib Treatmet of locally Anorexia, conjunctivitis,blepharitis,
advance or dry eye, haemorrhage, interstitial lung
metastatic NSCLC diseasae, diarrhea, vomiting, nausea,
who have activating dehydration, dry mouth, skin reaction,
mutations of the nail disorder, alopecia, asthenia,
EGFR TK pyrexia
 Protein (tyrosine kinase)
inhibitors
No. Zat aktif Indikasi Efek Samping
6 Imatinib Ph+ CML, GIST, Ph+ ALL, Neutropenia, thrombocytopenia,
mesilate myelodysplastic/myelopr anaemia, pancytopenia, febrile
oliferative disease neutropenia, anorexia, insomnia,
associated with PDGFR, dizziness, paraesthesia, taste
systemic mastocytosis, disturbance, hypoaesthesia,
hypereosinophilic Eyelid oedema, lacrimation
syndrome (HES) and/or increasedi conjunctival
chronic eosinophilic haemorrhage,
leukaemia (CEL), conjunctivitis, dry eye, blurred
unresectable recurrent vision, Flushing, haemorrhage
and/or metastatic DESP.
 Protein (tyrosine kinase)
inhibitors
No. Zat aktif Indikasi Efek Samping
8 Lenvatinib locally advanced or Hypertension, diarrhea, decreased
mesilate metastatic, appetite, weight decreased, fatigue,
differentiated nausea, proteinuria, stomatitis,
(papillary/follicular/H vomiting, dysphonia, headache,
rlrthle cell) thyroid palmar-plantar erythrodysaesthesia
carcinoma (DTC) syndrome (PPE).
9 Nilotinib HCl Treatment of Ph+ Comiting, myalgia, alopecia, muscle
CML spasms, decreased appetite, arthralgia,
bone pain, peripheral edema, asthenia
 Protein (tyrosine kinase)
inhibitors
No. Zat aktif Indikasi Efek Samping
10 Osimertinib locally advanced or diarrhoea , rash, Stomatitis,
mesilate metastatic epidermal keratitis, Interstitial lung
growth factor receptor disease, Platelet count
(EGFR) T790M mutation decreased, Leucocytes
positive non small cell decreased, Lymphocytes
lung cancer (NSCLC) who decreased, Neutrophils
have progressed on or decreased
after EGFR tyrosine kinase
inhibitor
 Protein (tyrosine kinase)
inhibitors
No. Zat aktif Indikasi Efek Samping
11 Ruxolitinib Myelofibrosis, including Anaemia,
Phosphate primary myelofibrosis, thrombocytopenia,
post-polycythemia vera neutropenia, bruising,
myelofibrosis or post- dizziness, headache, ALT
essential thrombocythemi increased, AST increased,
myelofibrosis hypercholesterolaemia
12 Sorafenib tosilate Advanced renal cell Diarrhoea, rash, alopecia
carcinoma, unresectable and hand-foot skin
hepatocellular carcinoma syndrome (palmar plantar
(HCC) erythrodyssaesthesia
syndrome)
 Protein (tyrosine kinase)
inhibitors
No. Zat aktif Indikasi Efek Samping
13 Sunitinib malate Gastrointestinal Diarrhea, hypertension,
stromal tumor (GIST) bleeding, mucositis, skin
and metastatic renal abnormalities.
cell carcinoma (MRCC)
14 Vemurafenib Unresectable or arthralgia, fatigue, rash,
metastatic melanoma photosensitivity reaction,
BRAF V600 mutation alopecia, nausea diarrhea,
positive headache, pruritus,
vomiting, skin papilloma
and hyperkeratosis
 ANTIBODI MONOKLONAL
No Zat aktif Indikasi Efek Samping
.
1 Bevacizumab Treatment of patients Gastrointestinal perforations,
(humanised anti- with metastatic haemorrhage, arterial
VEGF monoclonal carcinoma of the colon thromboembolism, leucopenia,
antibody) or rectum neutropenia, thrombocitopenia
2 Brentuximab Treatment of patients Infection : Upper respiratory tract
vedotin with relapsed or infection,
(antibody drug refractory : Hematologic : neutropenia,
conjugate (ADC) -CD30+ Hodgkin Nervous sytem disorder:
–anti CD30 lumphoma (HL), perripheral neurophaty,
-systemic anaplastic GI disorders: nausea, vomiting,
large cell lymphoma constipation
(sALCL).
 ANTIBODI MONOKLONAL
No. Zat aktif Indikasi Efek Samping
3 Nimotuzumab chemotherapy Chils, fatigue,
(Humanized anti-EGFR resistant high grade headache, nausea,
monoclonal antibody) gliomas in children/ increase SGPT,
adolescent vomiting
4 Pembrolizumab Treatment of GI : nausea,
(humanised monoclonal patients with: dhiarrhoea,
antibody which binds to the -unresectable or abdominal pain,
programmed cell death-1 (PD- metastastic vomiting
1) receptor) melanoma. Skin: rash, pruritus.
-advanced non Haematologic :
small cell lung anaemia
carcinoma (NSCLC)
 ANTIBODI MONOKLONAL

No. Zat aktif Indikasi Efek Samping

5 Pertuzumab Treatment of Infection: nasopharyngitis,
(humanised IgG1 patients with Haematologic: neutropenia,
monoclonal HER2-positive leucopenia, anaemia, febrile
antibody) metastatic or neutropenia
locally recurrent GI disorders: diarrhoea,
unresectable vomiting, stomatitis,
breast cancer in constipation, dyspepsia
combination with Nervous system disorder :
herceptin and neurophaty peripheral,
docetaxel. headache, dizziness
 ANTIBODI MONOKLONAL
No. Zat aktif Indikasi Efek Samping
6 Rituximab Treatment of patients Haematologic: neutropenia,
(human anti-CD20 with relapsed or leucopenia
monoclonal chemoresistant low- Immune sytem :
antibody) grade or folicular, CD angioedema
20-positive, B-cell non- GI disorders: nausea,
Hodgkin’s lymphomas Skin disorders : rash,
pruritis,
General : headache, fever,
chills, asthenia
 ANTIBODI MONOKLONAL
No. Zat aktif Indikasi Efek Samping
7 Trastuzumab Treatment of patients Infection : nasopharyngitis,
(humanised IgG1 with metastatic breast Haematologic disorders: febrile
anti-HER2 cancer whose tumours neutropenia, anaemia,
monoclonal overexpress HER2 neutropenia, leucopenia,
antibody) thrombocytopenia,
Nervous system disorder: tremor,
diziness, headache, paraesthesia,
Eye disorders : congjuctivitis,
lacrimation increased
8 Secukinumab the treatment of Infection : Upper respiratory tract
(Human IgG1/κ moderate to severe infection, oral herpes,
anti-IL-17A plaque psoriasis in GI disorders : diarrhoea
monoclonal adult patients
antibody)
 Other antineoplastic agents

No. Zat aktif Indikasi Efek Samping

Alkylating agents
1 Bendamustine HCl Leukemia limfositik hematological adverse
kronis, Non-Hodgkin reactions (leukopenia,
limfoma, Multiple thrombopenia),
myeloma dermatologic toxicities
(allergic reactions),
constitutional symptoms
(fever), gastrointestinal
symptoms (nausea,
vomiting)
 Other antineoplastic agents

No. Zat aktif Indikasi Efek Samping

Taxanes
1 Cabazitaxel Hormone refractory anaemia, leukopenia,
metastatic prostate neutropenia
cancer previously thrombocytopenia and
treated with diarrhoea
docetaxel-containing
regimen.
Immunomodulators
1 Fingolimod HCl Treatment of Headache, hepatic
(sphingosine 1- relapsing remitting enzyme increased,
phosphate multiple sclerosis diarrhoea, cough,
receptor influenza, sinusitis, back
modulator) pain
 Other antineoplastic agents
No. Zat aktif
2 Bortezomib
(reversible inhibitor of the
chymotrypsin-like activity of
the 26S proteasome)
Indikasi Efek Samping
Multiple nausea, diarrhoea,
myeloma; constipation, vomiting,
mantle cell fatigue, pyrexia,
lymphoma thrombocytopenia, anaemia,
neutropenia, peripheral
neuropathy (including
sensory), headache,
paraesthesia, decreased
appetite, dyspnoea, rash,
herpes zoster and myalgia
 EFEK SAMPING KEMOTERAPI

Alopecia
Mucositis

Pulmonary fibrosis

Nausea/vomiting Cardiotoxicity
Diarrhea
Local reaction
Cystitis
Renal failure
Sterility
Myalgia Myelosuppression
Neuropathy
Phlebitis
Efek samping kemoterapi.
1. Cepat (immediate)
2. Segera (early)
3. Lambat(delayed)
4. Sangat Lambat(late effect)
Onset Efek Samping Kemoterapi
Immediate : Efek samping yang terjadi dalam waktu
beberapa jam sampai beberapa hari setelah kemoterapi.
Contoh : Nausea/Vomiting, local tissue necrosis,
Phlebitis, Hyperuricemia, Skin rash, anaphylaxis,
demam&menggigil (bleomycin), hypotension (etoposide),
hypertension (Procarbazine).
Early : Efek samping yang terjadi dalam waktu beberapa
hari sampai beberapa minggu setelah kemoterapi.
Contoh : Leukopenia, Thrombocytopenia, Alopecia,
Stomatitis, Diarrhea, Hypercalcemia (esterogen),
Hypomagnesemia (cisplatin), DIC (asparaginase),
Hyperglycemia (corticosterid), ototoxicity (cisplatin),
Conjungtivitis (Methotrexate, Ara-C)
Delayed : Efek samping yang terjadi dalam waktu beberapa
minggu sampai beberapa bulan setelah kemoterapi.
Contoh :
Anemia, Aspermia, Hepatocellular damage,
Hyperpigmentation, pulmonary fibrosis.
Peripheral neuropathy (vincristine), Cardiac necrosis
(cyclophosphamide), Cholestatic jaundice (6-MP)
Late : Efek samping yang terjadi dalam waktu beberapa
bulan sampai beberapa tahun setelah kemoterapi.
Contoh :
Sterility, Premature menopause, Acute leukemia,
Lymphoma, solid tumor.
Hepatic cirrhosis (Mtx.), Osteoporosis (Corticosteroid),
Cataracts(busulfan)
 Emetogenic Potential Chemotherapy

High Emetogenic Moderate Emetogenic

• Cisplatin
• Mitomycin-C
• Dacarbazine
• Doxorubicin (low dose)
• Daunorubicin • Cyatarabine
• Methotrexate (high dose)
• Doxorubicin (moderate to high • Carboplatin
dose) • Mitoxantrone
• Ifosfamide
• Cyclophosphamide (high dose)
 Antiemetic for CINV
• Serotonin binds to 5HT3 receptors → efektif untuk akut
emesis. Dapat diberikan sebagai profilaksis
• 5HT3 inhibitor tidak efektif untuk delayed N/V
• Neuropeptide substance P → NK1-receptor antagonist :
aprepitant mempunyai efektifitas yang baik untuk delayed
N/V
• Kortikosteroid → dexametason sebagai kombinasi pada
5HT3 inhibitor.
 Mielosupresi
Hampir semua senyawa sitotoksik bersifat mielosupresif.
Titik nadir hari ke 8-16.
Leukopenia/Neutropenia : Risiko tinggi infeksi
Anemia : Fatique, lemas, oksigen 
Trombositopenia : Risiko tinggi perdarahan
Pemberian GC-SF untuk mencegah perburukan
mielosupresi pada pasien pasca kemoterapi.
Infeksi pada pasien kanker :
❖Aggressive chemotherapy terutama pada kasus – kasus
hematology cancer menyebabkan neutropenia.
❖Komponen sel darah putih (WBC) terutama Neutrophil
jumlahnya berkurang.
❖Pada Absolute Neutrophil Count (ANC ) < 0.5 x 109/L
pasien berresiko tinggi terkena infeksi.
❖Pada beberapa penelitian menunjukkan infeksi adalah
penyebab kematian pada sebagian besar kasus ALL dan
sebagian dari kasus Lymphoma.
❖Empirical therapy antibiotik dapat mengurangi resiko
tersebut.
Demam (Febrile)
Demam dapat disebabkan oleh obat chemotherapy,
blood transfusion, Infeksi, atau sel kanker (pada
leukemia).
Pada umumnya yang sering terjadi dan berbahaya
adalah Infeksi.

Senyawa chemotherapy yang menyebabkan demam :

Doxorubicin, L-Asparaginase, Azathioprine, Bleomycin,
Cyclophosphamide, Ara-C, Dacarbazine, Dactinomycin,
6-MP, Methotrexate, Vincristine, Vinblastine.
Jika suhu tubuh >38.5oC dan jumlah neutrophil
dibawah 1000, empirik AB harus dilakukan.
Infeksi dapat disebabkan oleh bakteri gram positif dan
gram negatif.
Pulmonary Toxicity :
Bleomycin
Fatal toxicity 1-2 %.
Risk Factor : Age > 70, concomitant radiotherapy, concurrent
cyclophosphamide, previous exposure to Bleomycin.
S/S : Dry cough, Dyspnea, tachypnea, fever, Cyanosis.
Outcome : with minimal changes, may recover if drug discontinue
Death occurs if hypoxemia present.
Mitomycin C
Incidence 2.8-12%
Risk Factor : Previously mitomycin therapy.
S/S : Progressive dyspnea, nonproductive cough, chest pain
Outcome : 40% die of progressive pulmonary insufficiency. 60%
recover after stopping mitomycin.
Nephro Toxicity :
Methotrexate : Monitor serum level untuk menentukan
leucovorin rescue.  Dosis jika Creatinine Clearance < 60
ml/min
Cyclophosphamide : Creatinine clearance < 25 ml/min →
dosis 50%
Cisplatin : Creatinine clearance < 50 ml/min → dosis 50%
Carboplatin : CrCl 41-49 ml/min : dosis 250 mg/m2
CrCl 16-40 ml/min : dosis 200 mg /m2
CrCl < 15 ml/min : sebaiknya tidak diberikan
Bleomycin : CrCl < 25 ml/min → dosis 50% - 75%
Etoposide : CrCl < 20 ml/min diberikan 75% dari dosis standar
Hepatotoxicity :
Manifestasi Hepatotoksik :
Me  enzym liver : asparaginase, carmustine, cytarabine,
dacarbazine, mercaptopurine, methotrexate, mitomycin.
Jaundice : Azathioprine, Busulfan, Mercaptopurine
Hepatic Fibrosis : Azathioprine, Cyclophosphamide
Necrosis Hepar : Asparaginase, azathioprine,
Cyclophosphamide, Methotrexate.
Bilirubin > 5 hentikan penggunaan : 5-Fu, Cyclophosphamide,
Methotrexate, daunorubicin, adriamycin, vinblastine,
vincristine.
SGOT >180 : Cyclophosphamide, Methotrexate 75% dosis,
Daunorubicin 50% dosis, Doxorubicin 25% dosis, Vincristine
dan vinblastine hentikan penggunaannya.
 dermatotoxicity
• Vesikan: vincristin, antracyclin
• Handfoot syndrome: 5 FU, Xelloda
• Rash :BCNU,Gemzar,procarbazine
• Photosensitive :DTIC,mitomycin
• Kuku berubah:cyclof, doxo,FU
• Hiperpigmentasi: doxo,5FU,
 Kardiotoksisitas.
• Pada antracyclin paling sering, obat
lain juga bisa al.cisplatin,
Cyclophosphamide,dll
• Akut : aritmia, perubahan EKG
• Kronik : kardiomiopati
• Late : CHF
Neurological Side-effect :
Vincristine : Peripheral neuropathy, seizure, nerve paresis
Vinblastine : Peripheral neuropathy, seizure, nerve
paresis
Cisplatin : Tinnitus, deafness, peripheral neuropathy
Asparaginase : Lethargy, confusion
Cyclophosphamide : drowsiness, lethargy
Methotrexate : Fits, encephalopathy
Taxan
Gastro Intestinal Toxicity

• Mucositis: doxorubicine,mtx,
bleomycin,5 FU

• Diare:5-fu, Cpt 11, mtx.,ara-c.

• Konstipasi: kadang kala bukan diare

tetapi konstipasi
Mucositis :
Senyawa chemotherapy yang sering menyebabkan
mucositis :
Methotrexate : efek  pada infus yang lama,
penurunan fungsi ginjal , dan radiasi.
5-Fu : efek  pada dosis tinggi, frekwensi, arterial
infusion.
Actinomycin-D : sangat sering menyebabkan
mucositis terutama jika bersamaan dengan radiasi.
Doxorubicin : efek  pada liver disease, dan radiasi
Bleomycin : mucositis hebat + ulcerative
Nyeri pada pasien kanker
Nyeri pada pasien kanker bisa disebabkan karena :
- Perkembangan sel kanker
- Terapi kanker ( chemotx. , radiasi, surgery )
- Penyakit yang timbul sebagai efek samping terapi.
- Sama sekali tidak berhubungan dengan kanker.
Nyeri sebagai efek samping dari kemoterapi sering terjadi
pada pemberian vinca alkaloid. Rasa nyeri dan panas (
burning ) terjadi pada kaki dan tangan.
Post steroid therapy pada hodgkin’s disease menimbulkan
nyeri pada sendi bahu dan lutut.
Mucositis sebagai efek samping chemotx. Menyebabkan
nyeri pada saat pasien makan, minum, dan berbicara.
 PENUTUP
• Pemberian kemoterapi pada pasien kanker harus
melibatkan multi disiplin
• Penetapan diagnosis yang pasti diperlukan untuk
menentukan modalitas terapi
• Monitoring pemberian kemoterapi diperlukan
untuk melihat potensial efek samping yang
terjadi dan efikasi pengobatan
TERIMA KASIH