Cancer Chemotherapy and Its Complication
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Transcript of Cancer Chemotherapy and Its Complication
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
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
Mode of delivery
• Central line• Peripherally inserted central catheter• Implantable port• Infusion pump
Intravenous chemotherapy Intrathecal chemotherapy via ommaya reservoir
Drug Delivery
Intracavity (intraperitoneal chemotherapy)
Chemotherapy delivery via PORT-A-CATH
IsoFlow drug delivery
Nanoparticle
HISTORY
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
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
PRINCIPLES OF CHEMOTHERAPY
CARCINOGENESIS
initiation
Promotion
Transformation and Proliferation
CELL CYCLE
Jillian H.Davis Department of Pharmacology Howard University
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
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.
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)
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
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
Responsiveness of tumors to chemotherapy
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
OVER EKSPRESI HER-2/neu PADA KANKER
Proliferasi tidak terkontrolPotensi metastasis meningkatResisten apoptosis
TRASTUZUMAB: menghambat dimerisasi HER-2
LAPATINIB menghambat tyrosine kinase intraseluler
TERAPI TARGET CML Abnormal BCR-ABL turn on cell growth & proliferation survival invasion metastasis angiogenesis
Imatinib mesylate
TERAPI HORMON PADA KANKER
TERAPI ANTIANGIOGENESIS
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
SCHEMATIC GLYCOPROTEIN
CHEMOTHERAPY SIDE EFFECTS
Anemia in cancer patients
Chemotherapy induced myelosuppression
PATHOGENESIS OF CINV
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
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
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
CHEMOTHERAPY TOXICITIES based on COMMON TERMINOLOGY CRITERIA of ADVERSE EVENTS
Extravasation of anthracyclin
Day-1 Day-4 Day -8
Day-10 Day-14 Day-16
FINISH