Chemotherapy 7 anticancer agents

CHEMOTHERAPYHIGHLIGHTS

MOHAMED BAHR; MD, PHD

Anticancer Drugs

Mohamed Bahr; MD, PhD

CANCER CHEMOTHERAPY






I. ALKYLATING AGENTS (CCNS)Cyclophosphamide, Busulphan – Nitrosoureas – Cisplatin.

They are chemical substances containing highly reactive

groups (alkyl). They transfer these active groups to various

cellular constituents, mainly DNA, proteins and enzymes

decreasing their synthesis and/ or function.



II. ANTIMETABOLITES (S PHASE)They are structural analogs of naturally occurring metabolites

competing with them for enzyme systems → ↓ DNA and RNA

synthesis.

A. 6- Mercaptopurine (purine antagonist)

Decreases purine synthesis → ↓ DNA and RNA synthesis.

B. Methotrexate (folic acid antagonist)

Inhibits DHFR → ↓ H4F synthesis → ↓ DNA and RNA synthesis.




III. NATURAL PRODUCTSA. Plant alkaloids: (Vinblastine, Vincristine) (M phase)

They are mitotic spindle poisons → mitotic arrest.




B. Antibiotics

Bind to DNA → fragmentation of its strands → ↓ DNA

synthesis.

Bleomycin (G2 - M)

Dactinomycin - Adriamycin - Mitomycin - Doxorubicin (CCNS)





C. Camptothecins (topoisomerase I inhibitors) (CCNS)

Irinotecan - Topotecan




D. Epipodophyllotoxin (topoisomerase II inhibitor) (G1–S

phase)

Etoposide




E. Taxanes (M phase)

Paclitaxel




F. Enzymes (L- asparaginase)

↓ Blood asparagine → deprives tumor cells of this amino acid

which is essential for protein synthesis.




G. Interferons

See Before


IV. HORMONES AND ANTAGONISTSCorticosteroids in leukemia and lymphomas.

Testosterone in cancer breast.

Estrogen in cancer prostate.

Hormone receptors agonists and antagonists:

(estrogen/tamoxifen), (testosterone/cyproterone, flutamide).

GnRH agonists (leuprolide and goserelin) for prostate and

breast tumors.





V. MISCProtein tyrosine kinase inhibitors: Imatinib

Immunomodulators: Thalidomide


ADVERSE EFFECTSA. GENERALBone marrow depression: leucopenia, thrombocytopenia or pancytopenia.

Hair loss.

GIT disturbances: vomiting, diarrhea and GIT ulcers.

Hyperuricemia (due to destruction of ↑number of tumor cells).

Immunosuppression: liability to infections and delayed healing of wounds.

Gonadal damage: sterility, amenorrhea and azospermia.

Teratogenicity and mutagenicity.

Secondary malignancy.



B. SPECIFICCyclophosphamide: hemorrhagic cystitis.

Busulphan: interstitial pneumonitis and pulmonary fibrosis.

Methotrexate: hepatotoxic, nephrotoxic, neurotoxic & folate

deficiency

Vinca alkaloids: peripheral and autonomic neuropathy.

Bleomycin: pulmonary fibrosis – skin pigmentation.


REFERENCESLippincott’s Illustrated Reviews, 5th ed.

Color Atlas of Pharmacology, 2nd ed.

Goodman and Gilman's The Pharmacological Basis of

Therapeutics, 12th ed.

Health & Medicine

Chemotherapy 7 anticancer agents