Download - Cancer Chemotherapy and Its Complication
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CANCER CHEMOTHERAPY
Kartika Widayati Taroeno-Hariadi Division Of Hematology and Medical Oncology
Department of Internal Medicine Faculty of Medicine Universitas Gadjah MadaDR SARDJITO HOSPITAL
YOGYAKARTA
Lecture for PSIK
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Definition of chemotherapy
• The use of synthetic chemical to destroy infective agents also applied to inhibit growth of malignant or cancerous cells within the body
• Route: oral, intravena, intraarterial, subcutan intraperitoneal, intravesical (Intracavity), intrathecal, topical
• New route of delivery: isolated infusion, targeted delivery, nanoparticle, minicell
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Mode of delivery
• Central line• Peripherally inserted central catheter• Implantable port• Infusion pump
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Intravenous chemotherapy Intrathecal chemotherapy via ommaya reservoir
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Drug Delivery
Intracavity (intraperitoneal chemotherapy)
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Chemotherapy delivery via PORT-A-CATH
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IsoFlow drug delivery
Nanoparticle
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HISTORY
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Key advances in the history of cancer chemotherapy.
DeVita V T , Chu E Cancer Res 2008;68:8643-8653
©2008 by American Association for Cancer Research
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Key advances in the history of cancer chemotherapy.
DeVita V T , Chu E Cancer Res 2008;68:8643-8653
©2008 by American Association for Cancer Research
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PRINCIPLES OF CHEMOTHERAPY
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CARCINOGENESIS
initiation
Promotion
Transformation and Proliferation
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CELL CYCLE
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Jillian H.Davis Department of Pharmacology Howard University
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Cell cycle specific agents1.Anti metabolits2.Bleomycin3.Podophylin alkaloids4.Plan alkaloids
Cell cycle non specific agents1.Alkylating agents2.antibiotic3.Cisplatin4.Nitrosurea
Cell cycle and drug activity
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Population kinetics
• Tumor growth depends on the size of the proliferating pool of cells and the number of cells dying spontaneously
• The larger the tumor mass, the greater the percentage of non dividing and dying cells, and the longer it takes for the average cell to devide.
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Drugs Used in Cancer Chemotherapy
• Cytotoxic Agents– Alkylating Agents– Antimetabolites– Cytotoxic antibiotics– Plant derivatives
• Hormones– Suppress nat’l hormone secr’n or antagonize
hormone action
• Misc (mostly target oncogene products)
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Indication of cancer chemotherapy
• To cure certain malignancies• To palliate symptoms• To treat asymptomatics patients: when the
cancer is aggressive and treatable, when treatment has been proved to decrease the rate of relapse and increase the disease free survival and overall survival
• To allow less mutilating surgery
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CONTRAINDICATION OF CHEMOTHERAPY
• When facilitaties are inadequate to evaluate the patients’ response to therapy and to monitor and manage toxic reactions
• When the patient is not likely to survive longer even if tumor shrinkage could be accomplished
• When the patients is not likely to survive long enough to obtain benefits from the drugs
• When the patients is asymptomatic with slow growing, incurable tumors, in which case chemotherapy should be postponed untill symptoms require palliation
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Responsiveness of tumors to chemotherapy
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TERAPI TARGET
Molecular Targeted Therapy merupakan pendekatan terbaru terapi kanker
Karakter : Terapi ditujukan pada molekul targetMolekul target harus secara unik terekspresi pada sel-sel kankerMolekul target penting untuk mempertahankan fenotipik malignansi
1. cell-signaling targeted therapy2. Angiogenesis targeted therapy3. Protein degradation targeted therapy4. Immune modulation5. Phenotype-directed targeted therapy
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OVER EKSPRESI HER-2/neu PADA KANKER
Proliferasi tidak terkontrolPotensi metastasis meningkatResisten apoptosis
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TRASTUZUMAB: menghambat dimerisasi HER-2
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LAPATINIB menghambat tyrosine kinase intraseluler
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TERAPI TARGET CML Abnormal BCR-ABL turn on cell growth & proliferation survival invasion metastasis angiogenesis
Imatinib mesylate
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TERAPI HORMON PADA KANKER
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TERAPI ANTIANGIOGENESIS
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Resistance to Cytotoxic Drugs
increase expression of MDR-1 gene for a cell surface glycoprotein P glycoprotein MDR-1 gen is involved in drug eflux Drug that reverse multidrug resistance include verapamil, quinidine, cyclosporin MDR increases resistance to natural products such as anthracyclins, vinca alkaloid, epipodophylotoxins
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SCHEMATIC GLYCOPROTEIN
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CHEMOTHERAPY SIDE EFFECTS
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Anemia in cancer patients
Chemotherapy induced myelosuppression
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PATHOGENESIS OF CINV
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CLASSIFICATION OF CINV
Acute Occurs and resolves within 24 hours of chemotherapy
Generally peaks with 5-6 hours
Delayed Occurs 1-6 days after chemotherapy
Common with administration of cisplatin, carboplatin, cyclophosphamide, doxorubicine
Anticipatory Conditioned response after prior, inadequately controlled CINV, nausea more common than vomiting
Tavorath and Hesketh.Drug 1996;52:639
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RISK FACTOR FOR CINV
TREATMENT RELATED PATIENT RELATED
Emetogenecity of single agent
Emetogenecity of regiment
High drug dose
Female
Younger age
Low / no alcohol use
Previous CINV
History of motion sickness
Hyperemesis of pregnancy
Hesketh. NEngl J Med 2008; 358:23
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EMETOGENICITY
Minimal <10% Low 10-30 % Moderate 30 -90% High >90%
Alemtuzumab
Asparaginase
Bevacizumab
Cetuximab
Rituximab
Vinblastin
Vincristin
Vinorelbin
Capecitabine
5-FU
Etoposide
Fludarabine
Etoposide
Gemcitabine
Paclitaxel
Pemetrexed
Topotecan
Arsenic trioxide
Carboplatin
Cyclophos -
phamide < 1500 mg/m2
Cytarabine
Doxorubicine
Epirubicine
Ifosfamide, Oxaliplatin
Irinotecan
temozolamide
AC
Carmustine
Cisplatin
Dacarbazine
Mechloretamine
Streptozocine
Cyclophosphamide > 1500 mg/m2
Hesketh. NEngl J Med 2008; 358:23
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CHEMOTHERAPY TOXICITIES based on COMMON TERMINOLOGY CRITERIA of ADVERSE EVENTS
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Extravasation of anthracyclin
Day-1 Day-4 Day -8
Day-10 Day-14 Day-16
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FINISH
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