Download Cancer chemotherapy

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
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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
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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
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