Handling Sitostatika

Alexander Rendi A., S.Farm, Apt.

November 2018
CT SCAN ABDOMEN
Maret 2019
CT SCAN ABDOMEN
Ca Pankreas
Guidelines
 Siklus Mitosis sel
• G0 phase: resting state
• G1 phase: cell prepares for DNA synthesis
• S phase: cell generates complete copy of genetic material
• G2 phase: cell prepares for mitosis
• M phase: replicated DNA is condensed and segregated into
chromosomes
Mekanisme Kerja Obat Kanker
 Hormonally Active Agents
• Antiandrogen • Adrenocorticosteroids
• Flutamide • Hydrocortisone
• Prednisone
• Antiestrogen
• Tamoxifen • Gonadotropin-releasing hormone agoinsts
• Goserelin acetate
• Progestins • Leuprolide
• Megestrol acetate
• Aromatase inhibitors
• Aminoglutethimide
• Anastrozole
• Exemestane
• Letrozole
GROWTH FACTOR RECEPTOR
INHIBITORS
• Cetuximab (erbitux)  menghambat The epidermal growth factor receptor (EGFR) ada
colo-rectal cancer (EGFR pertumbuhan, proliferasi, metastase, angiogenesis agent)
• Gefitinib (Iressa) and erlotinib (Tarceva) small molecule inhibitors of the tyrosine
kinase yg berhub dgn EGFR pada non-small cell lung cancer
• Bevacizumab (avastin) anti Vascular Endothelial Growth Factor (VEGF) is one of the
most critical angiogenic growth factors.  colorectal
 PEMBERIAN KEMOTERAPI
• STRATEGI RUTE
1. •Tunggal/•Kombinasi 1. Oral
2. Mekanisme kerja beda 2. Intravena
3. Efek toksik berbeda 3. Intramuskular (MTX)
4. Mekanisme resistensi berbeda 4. Intratekal (MTX, AraC)
5. Optimal : dosis, jadwal 5. Intraperitoneal (Zoladex)
6. Cegah timbul sel resisten 6. Intrapleura (Bleocyn)
7. Intraarterial
8. Intraperikardial
9. Intravesicalia (Mitomycin)
10. TACE (Trans Arterial Chemo Embolization) Doxo-
Mitomicyn
PRINCIPLES OF CHEMOTHERAPY DRUGS MECHANISM
Resti Mulya Sari-Divisi Hematologi Onkologi Medik-Rumah Sakit Kanker Dharmais
 Alkylating Agent
• (Cyclophosphamide, Ifosfamide)
• Alkylating agents work by reacting with the proteins that bond together to form the very delicate
double helix structure of a DNA molecule, adding an alkyl group to some or all of them. This prevents
the proteins from linking up as they should, causing breakage of the DNA strands and, eventually, the
death of the cancer cell. This phenomenon is essentially a mutation that takes away the cancer cell’s
ability to multiply.
• Alkylating chemotherapy drugs have this effect on a cancer cell during every phase of its life cycle,
making them desirable for use on a wide range of cancers.
 Hemorrhagic cystitis acrolein metabolit dari siklofosfamid dan ifosfamid  mengiritasi saluran
kemihpendarahan.
 Pencegahan : hidrasi, pemberian MESNA (berikatan dg acrolein metabolit 80-120% dari dosis sediaan)
 Platinum Base Chemotherapy
• (Cisplatin, Carboplatin, Oxaliplatin)
• Platinum compounds cause apoptosis of cancer cells through changes in DNA
structure, which inhibits DNA replication, transcription and cell division (the cell
cycle).
 Nephrotoxicity hidrasi 24 jam, nerve damage (neurotoxicity).
 High emetogenic
 Dose limiting toxicity (acute dan delayed N/V) Toxicity cisplatin > carboplatin >
oxaliplatin,
 sebisa mungkin gunakan D5.
 Koreksi K, Mg.
 Antimetabolite
• Antimetabolites induce cell death during the S phase of cell growth when
incorporated into RNA and DNA or inhibit enzymes needed for nucleic acid
production.
• Myelosupressive
 Folic acid antagonis : methotrexate, pemetrexate (Antidote dengan Leucovorin)
 Pyrimidine analog : 5 Fu, cytarabine, gemcitabine
 Purine analog : Fludarabine
 Pemetrexate : skin rash, stomatitis, N/V Pencegahan : premedikasi dg. Vit B12 1
minggu sblm pemberian sampai pada hari pemberian.
 Hand Foot Syndrome – 5 Fluorouracil-Xeloda  salep urea
Hand Foot Syndrome
 Anthracycline
• Doxorubicin (“red devil chemo”) , Daunorubicin, Idarubicin, Epirubicin
• These drugs are non-cell-cycle specific.
• Intercalation anthracyclines into DNA leading to inhibition of macromolecular synthesis.
• Binding of anthracyclines to proteasomes also inhibits the protease activity leading to inhibition of degradation of proteins
involved in cell growth and metabolism and thus inducing apoptosis of neoplastic cells.
• Doxorubicin has been demonstrated to induce the binding of p53 to DNA. As p53 is a major player in some forms of
apoptosis, it has been proposed that anthracyclines may exert their cytotoxic effect via p53 mediated apoptosis.
 Cardiotoxicity acumulative dose 450 –550 mg. Dosis Kumulatif  seumur hidup Anthracycline Doxorubicin < 550 mg/m2,
Daunorubicin 550mg/m2 Epirubicin 900 mg/m2  echo jantung
 Highly Vessicant
 Discoloration pada urine dan body fluid lain
 Dose reduction pada hepatic dysfunction
 Vinca Alkaloid
• Vincristine, Vinblastine, Vinorelbine
• Vinca Alkaloids halt the division of cells and cause cell death.
• During cell division, vinca alkaloid molecules bind to the building blocks of a protein called tubulin,
inhibiting its formation. The drugs work during the M-phase of cell reproduction. Tubulin protein
normally works in cells to create “spindle fibers” (also called microtubules). These microtubules
provide cells with both the structure and flexibility they need to divide and replicate. Without
microtubules, cells cannot divide. The vinca alkaloid’s mechanism in a nutshell: by occupying
tubulin’s building block structure, vinca alkaloids prevent cancer cells from successfully dividing.
 Tidak boleh diberikan intra thekal !!!  FATAL
 Bone Marrow Depression, Neurotoxic, Ototoxic (saraf pendengaran-keseimbangan di Intracranial)
 Potensial vescicant pemberian bolus 6-10 menit.
 Taxanes
• Paclitaxel, Docetaxel
• The taxanes are mitotic inhibitors, meaning that they inhibit tumors primarily by preventing cells from
entering mitosis, a process of cell division. The taxanes accomplish this by inhibiting microtubule polymerization.
In addition, taxanes appear to stimulate apoptosis, or programmed cell death, which is often inhibited in cancer
cells.
• Antiangiogenesis (cocok untuk tumor solid)
 Irritant : pelarut (PEG) – wajib antihistamin-steroid
 Hematology disorder
 Docetaxel : peripheral edema premedikasi dg dexamethasone (D-1, D, D+1)
 Non PVC Infus set
 Monoclonal Antibody
• Monoclonal Antibody Immunoterapi-Terapi Target Trastuzumab, Rituximab,
Nimotuzumab, Infliximab, Cetuximab, Bevacizumab
 Menginduksi sistem imun, waspada alergi wajib antihistamin-Steroid +
antipiretik bila perlu (paracetamol)
 Sediaan mudah berbuih, jangan terkocok.
Monoclonal
Antibody
 Contoh Kemoterapi Tumor
Diagnosis Current Treatment of Choice Other Valuable Agents
(1) Adjuvant chemotherapy or tamoxifen after Cyclophosphamide, doxorubicin, vincristine,
primary breast surgery methotrexate, fluorouracil, paclitaxel,
Carcinoma of breast
(2) Combination chemotherapy or hormonal mitoxantrone, prednisone,1 megestrol,
manipulation for late recurrence androgens,1 aminoglutethimide, trastuzumab
Lomustine, cyclophosphamide, doxorubicin,
Radiation plus cisplatin (localized), cisplatin,
Carcinoma of cervix methotrexate, mitomycin, bleomycin,
carboplatin (metastatic)
vincristine, interferon, 13-cis-retinoic acid
Carcinoma of colon Fluorouracil plus leucovorin plus oxaliplatin Irinotecan
Carcinoma of
Progestins or tamoxifen Doxorubicin, cisplatin, carboplatin
endometrium
Methotrexate, vincristine, vinblastine,
Carcinoma of lung Cisplatin plus taxane
doxorubicin, mitomycin C
Cyclophosphamide, doxorubicin, melphalan,
Carcinoma of ovary Cisplatin or carboplatin plus paclitaxel
fluorouracil, vincristine, altretamine, bleomycin

Doxorubicin, or methotrexate with leucovorin Cyclophosphamide, dacarbazine, interferon,

Osteogenic sarcoma
rescue initiated after surgery ifosfamide plus mesna1

1Supportiveagent, not oncolytic.

2Investigational agent.
Treatment available through qualified investigators and centers authorized by National Cancer Institute and
Cooperative Oncology Groups.
 Contoh Kemoterapi Kanker Darah
Diagnosis Current Treatment of Choice Other Valuable Agents

Induction: vincristine plus prednisone.

Asparaginase, daunorubicin, carmustine,
Remission maintenance: mercaptopurine,
Acute lymphocytic leukemia doxorubicin, cytarabine, allopurinol,1
methotrexate, and cyclophosphamide in various
craniospinal radiotherapy
combinations

Methotrexate, thioguanine, mercaptopurine,

Acute myelocytic and Combination chemotherapy: cytarabine and
allopurinol,1 mitoxantrone,
myelomonocytic leukemia mitoxantrone or daunorubicin or idarubicin
azacitidine,2 amsacrine,2 etoposide

Chlorambucil and prednisone (if indicated),

Chronic lymphocytic leukemia Allopurinol,1 doxorubicin, cladribine
fludarabine

Chronic myelogenous Imatinib, busulfan, or interferon, bone marrow Vincristine, mercaptopurine, hydroxyurea,
leukemia transplantation (selected patients) melphalan, interferon, allopurinol1

1Supportiveagent, not oncolytic.

2Investigational agent.
Treatment available through qualified investigators and centers authorized by National Cancer Institute and
Cooperative Oncology Groups.
 Contoh regimen kemoterapi
• TPF (docetaxel, cisplatin, 5-FU) – ca kepala & leher
• CHOP (cyclo, doxorubicin, vincristine, prednisone) : NHL (Non-Hodgkin Limphoma)
• TAC (docetaxel, doxorubicin, cyclophosphamide) : ca payudara
• 6 FEC 100 (fluorouracil, epirubicin, cyclophosphamide) : ca payudara
• Gemcitabine/paclitaxel : ca payudara
• Paclitaxel/carboplatin : NSCLC (Non Small Cell Lung Cancer)
• FOLFOX4 (fluorouracil, leucovorin, oxaliplatin) : ca kolorektal
• Paclitaxel (dose-dense)/carboplatin : ca ovarium
• Gold standar : regimen 3 – 7 Kombinasi : Antrasiklin 3 hari + Sitarabin 7 hari : Acute Myeloid Leukimia
• Sitarabin dosis tinggi + rituximab, Metotreksat dosis tinggi + rituximab, termasuk metroteksat intratekal :
Lymphoblastic Limphoma , Myeloblastic Leukemia Relapse
 Penunjang kemoterapi
1. Ranitidin – Gastridin, Zantac
2. Dexamethasone (mual muntah-kombinasi pada 5HT3 Inhibitor + ↑ kinerja obat
3. Antimual (Ondansentron, Granisetron, Tropisetron, Ramonosetron, Palonosetron)
4. Difenhidramin HCl  antihistamin (Taxanes, Monoclonal Antibody)
5. Leucovorin (bone marrow rescue) 5-fluorouracil, metothrexate)
6. Mesna – uromitexan  Hemorrhagic cystitis (Cyclophosphamide, Ifosfamid)
7. Allopurinol – Tumor Lysis Syndrome (leukimia)
8. Filgrastim – Leucogen, Leucokine, Neupogen, (Neutropenia) (kerja pendek)
9. Lenograstim – Granocyte (Neutropenia) (kerja pendek)
10. Pegfilgrastim – Neulastim (Neutropenia) (kerja panjang)
11. Epoetin Alfa – Epprecx, Recormon, Hemapo (Eritropenia-Anemia)
12. Peginterferon alfa 2a – Pegasys (Immunomodulator) ↑ fagosit makrofag & increasing p53 activity, which kills virus-infected
cells & Cancer cells by promoting apoptosis.
 Pemantauan Kemoterapi
PRE KEMOTERAPI + PERSIAPAN - Pantau saat pemberian kemoterapi (kemungkinan reaksi
• - Identitas pasien dan status (PPTM, Lab, Biaya) alergi dan efek samping
• - Peresepan, pengantar, protokol
• - Perlengkapan obat kemoterapi (set khusus, IV chat, PASCA PEMBERIAN KEMOTERAPI
port) •- Pembuangan sisa obat / peralatan kemoterapi
• - Penyimpanan, Dosis, ED, Pelarut, Volume, Stabilitas •- Evaluasi pasien (laboratorium)
Obat (Kemasan + label) •- Pencatatan (intake + output) ginjal
• - Premedikasi •- Terapi suportif (optional)

“Manipulating and reconstituting cytotoxics poses the

greatest risk”

PEMBERIAN KEMOTERAPI
- Evaluasi akses iv
- Flush antar pemberian obat kemoterapi
- Perhatikan urutan pemberian obat kemoterapi
(Vesiccant, irritant, Non Vesiccant Irritant)
Penanganan Ekstravasasi obat vesikan
Antiemesis, NCCN guidelines 2015
Contoh Staging Lymphoma
Contoh Protokol