KEMOTERAPI PADA PASIEN

KANKER
APA ITU KEMOTERAPI
SEL KANKER VS SEL NORMAL
Modalitas Pengobatan Kanker
Operas
i
Loka
l
Radiasi

Terapi Kanker
Kemoterapi

Sistemik Hormon
Terapi

Immunoterap
i
Tujuan Pemberian
Kemoterapi
Ajuva
n
Kurati
f
Tujuan Neo
Pemberian Ajuvan
Kemotera
pi
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 Kondis • Usia
• Comorbi
i d
Pasien disease
• Jenis kanker
Jenis • Lokasi
organ
Penyaki • Stadium
t • Derajat
Keganasa
Stadium n
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 • Carboplatin
antineoplastic 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,
Antitumou •Daunorubicin, •Mitoxantrone,
r •Doxorubicin, •Plicamycin,
Antibiotics •Epirubicin, •Valrubicin
•Vinblastine,
•Vincristine,
Plant alkaloid •Vinorelbine
•Vindesin Sulfat
•Etoposide
•Mitotane, • Asparaginase
•Omacetaxine, (Pegaspargas
•Pomalidomide, e),
Miscellaneou •Tagraxofusp, •Bexarotene,
s agent •Telotristat, •Eribulin,
•Temsirolimus, •Everolimus,
•Thalidomide, •Hydroxyurea,
•Venetoclax •Ixabepilone,
•Lenalidomide,
•Paclitaxel
Taxane •Docetaxel
 Protein (tyrosine kinase)
inhibitors
No. Zat aktif Indikasi Efek Samping
1 Afatinib dimaleate Treatment of locally Diarrhea, stomatitis,
advanced or nausea, vomiting,
metastatic non- rash, paronychia,
squamous NSCLC
2 Crizotinib Treatment of ALK Vision disorders, nausea,
positive advance diarrhea, vomiting,
NSCLC edema, constipation,
elevated transaminase,
fatigue, decreased
appetite, dizziness,
neuropathy
 Protein (tyrosine kinase)
inhibitors
No. Zat aktif Indikasi Efek Samping
3 Axitinib Tratment of diarrhoea, hypertension,
renal cell fatigue, decreased appetite,
carcinoma 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 keratitis, conjunctivitis,
metastatic NSCLC epistaxis, gastrointestinal
with EGFR activating bleeding, aliopecia, dry
mutations skin, paronychia,
Folliculitis, Acne/
Treatment of locally Dermatitis acneiform,
advance , Skin fissures
unresectable or
metastatic 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
metastatic NSCLC lung diseasae, diarrhea, vomiting,
who have nausea, dehydration, dry mouth, skin
activating reaction, nail disorder, alopecia,
mutations of the asthenia, pyrexia
EGFR TK
 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,
associated with PDGFR, insomnia, dizziness,
systemic mastocytosis, paraesthesia, taste disturbance,
hypereosinophilic hypoaesthesia, Eyelid oedema,
syndrome (HES) and/or lacrimation increasedi
chronic eosinophilic conjunctival haemorrhage,
leukaemia (CEL), conjunctivitis, dry eye, blurred
unresectable recurrent vision, Flushing, haemorrhage
and/or metastatic DESP.
 Protein (tyrosine kinase)
inhibitors
No. Zat aktif Indikasi
8 Lenvatini locally advanced or
b metastatic,
mesilate differentiated
(papillary/follicular/H
rlrthle cell) thyroid
carcinoma (DTC)
9 Nilotinib HCl Treatment of Ph+
CML
Efek Samping
Hypertension, diarrhea, decreased
appetite, weight decreased, fatigue,
nausea, proteinuria, stomatitis,
vomiting, dysphonia, headache,
palmar-plantar erythrodysaesthesia
syndrome (PPE).
Comiting, myalgia, alopecia, muscle
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,
mesilate metastatic epidermal Stomatitis, keratitis,
growth factor receptor Interstitial lung disease,
(EGFR) T790M mutation Platelet count decreased,
positive non small cell Leucocytes decreased,
lung cancer (NSCLC) who Lymphocytes decreased,
have progressed on or Neutrophils decreased
after EGFR tyrosine
kinase inhibitor
 Protein (tyrosine kinase)
inhibitors
No. Zat aktif Indikasi Efek Samping
11 Ruxolitini Myelofibrosis, including Anaemia,
b primary myelofibrosis, thrombocytopenia,
Phosphat post-polycythemia vera neutropenia, bruising,
e myelofibrosis or post- dizziness, headache, ALT
essential thrombocythemi increased, AST
myelofibrosis increased,
hypercholesterolaemia
12 Sorafenib tosilate Advanced renal cell Diarrhoea, rash, alopecia
carcinoma, unresectable and hand-foot skin
hepatocellular carcinoma syndrome (palmar
(HCC) plantar
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
positive diarrhea, 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 thromboembolism, leucopenia,
antibody) colon or rectum neutropenia,
thrombocitopenia
2 Brentuximab Treatment of patients Infection : Upper respiratory tract
vedotin with relapsed or infection,
(antibody drug refractory : Hematologic :
conjugate -CD30+ Hodgkin neutropenia, Nervous
(ADC) lumphoma (HL), sytem disorder:
–anti CD30 -systemic perripheral neurophaty,
anaplastic large GI disorders: nausea,
cell lymphoma vomiting,
(sALCL). constipation
 ANTIBODI MONOKLONAL
No. Zat aktif Indikasi Efek Samping
3 Nimotuzumab chemotherapy Chils, fatigue,
(Humanized anti- resistant high headache,
EGFR monoclonal grade gliomas in nausea, increase
antibody) children/ SGPT, vomiting
adolescent
4 Pembrolizumab Treatment of GI : nausea,
(humanised monoclonal patients with: dhiarrhoea,
antibody which binds to -unresectable abdominal
the or metastastic pain, vomiting
programmed cell death-1 melanoma. Skin: rash, pruritus.
(PD- -advanced non Haematologic :
1) receptor) small cell lung anaemia
carcinoma
(NSCLC)
 ANTIBODI MONOKLONAL

No. Zat aktif Indikasi Efek Samping

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

8 Secukinumab the treatment of Infection : Upper respiratory

(Human moderate to tract infection, oral herpes,
IgG1/κ anti-IL- severe plaque GI disorders : diarrhoea
17A psoriasis in adult
monoclonal 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 fatigue, pyrexia,
cell thrombocytopenia, anaemia,
lymphoma neutropenia, peripheral
neuropathy (including
sensory), headache,
paraesthesia, decreased
appetite, dyspnoea, rash,
herpes zoster and myalgia
 EFEK SAMPING
KEMOTERAPI

Alopecia
Mucositis

Pulmonary fibrosis

Nausea/vomitin Cardiotoxicity
g
Local reaction
Diarrhea
Cystitis Renal failure
Sterility Myelosuppression
Myalgia
Phlebitis
Neuropath
y
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
Hyperglycemia (corticosterid),
(asparaginase),
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
• Dacarbazine • Mitomycin-C
• 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.
 Mielosupres
i
Hampir semua senyawa sitotoksik bersifat mielosupresif.
Titik nadir hari ke 8-16.
Leukopenia/Neutropenia : Risiko tinggi infeksi
Anemia : Fatique, lemas, oksigen 
Trombositopeni : Risiko tinggi perdarahan
a
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.
 PENUTU
•
P
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