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Dr.Sherif Shaltout 20/5/2014 Cancer chemotherapy The available lines for treatment of cancer are Radiation Therapy: Surgery Chemotherapy Hormone Therapy Immunotherapy Indications of anticancer drugs: 1-Neoadjuvant chemotherapy (preoperative treatment): initial chemotherapy is designed to shrink the primary tumor 2-Adjuvant chemotherapy (postoperative treatment): when there is risk of recurrence. 3- Curable in diffuse non resectable neoplasms: in certain types of cancer as Hodgkin's and non-Hodgkin's lymphoma Mode of action of anticancer drugs: They act by inhibition of cell multiplications through interruption of cell cycle which consists of: 1- Go phase: resting state: cell is not dividing 2-G1 phase: synthesis of enzymes needed for DNA synthesis. 3-G2 phase: synthesis of cellular components required for mitosis. 4-S phase: DNA is replicated 5-M phase : Protein synthesis and mitosis The rapidly dividing cells are more sensitive to anticancer drugs while nonproliferating cells usually survive toxic effects of chemotherapy. Cytotoxic drugs l)-Antimetabolites -They interfere with the availability of normal purine or pyrimidine nucleotide precursors …..> inhibit DNA or RNA synthesis. -cytotoxic effects are S- phase cell cycle specific. Folic acid antagonists: Methotrexate Purine analogues : 6-Mercaptopurin (6MP)- Fludarabine Pyramidine analogues: 5-flurouracil 2)-Alkylating agents -They act by alkylation of DNA which is lethal effect to the tumor cell - Cyclophosphamide- Cisplatin 3)- Natural products 1- Antibiotics - produce Oxygen free radicals which bind to DNA causing DNA breaks. - Doxorubicin- Bleomycin 2- Plant alkaloids A-Mitotic spindle inhibitors 1-Vinca alkaloid Vincristine -Vinblastin. 2-Taxol: Paclitaxel, Docetaxel. B-Topomerase-II inhibitors: Etoposide 1 Dr.Sherif Shaltout 20/5/2014 4- Miscellaneous: 1-Tyrosine kinase inhibitors Imatinib. 2- Hydroxyurea Cytotoxic drugs: subdivided into Cell- cycle specificity of drugs: Antimetabolites- Bleomycin- vinca alkaloids. Cell- cycle non- specific drugs: other anticancer drugs. Hormonal therapy Estrogen antagonists e.g. tamoxifen , raloxifiene or androgen are used in cancer breast . Androgen antagonists e.g. flutamide or estrogen used in cancer prostate. Somatostatin analogues e.g. octreotide used in Zollinger-Ellison syndrome. Corticosteroids are used in leukemia Immunotherapy: Rituximab – Cetuximab - interferon alpha1, 2 *Adverse effects of cytotoxic drugs: 1)- Common: vomiting- stomatitis- alopecia- bone marrow depression 2)- Specific: 1- Methotrexate: immunosuppression 2- Doxorubicin: cardiotoxicity 3- Cyclophosphamide: cystitis, immunosuppression 4- Bleomycin: pulmonary fibrosis 2