• Vinblastine -- (Velban)

  • Mechanism of action: microtubule depolymerization

    • Mitotic arrest at metaphase; interferes with chromosome segregation

  • Clinical Use::

    • Systemic treatment of Hodgkin's disease

    • Lymphomas

  •  Adverse Effects:

    • Nausea

    • Vomiting

    • Alopecia

    • Bone marrow suppression

• Vincristine -- (Oncovin)

  • Mechanism of action: microtubule depolymerization

    • Mitotic arrest at metaphase; interferes with chromosome segregation

  • Clinical Use::

    • In combination with prednisone: induction of remission in children with acute leukemia

    • Useful in treating some other rapidly proliferating neoplasms

  •  Adverse Effects:

    • Significant frequency of neurotoxic reactions

    • Occasional: bone marrow depression

• Podophyllotoxins (etoposide {VP- 16}and teniposide {VM-26})

  • Etoposide and teniposide: structurally similar

  • Mechanism of action: Block cell cycle: in late S-G2 phase

    • Inhibition of topoisomerase II -- DNA damage

  • IV administration

  • Urinary excretion; some in bile

  • Clinical Use:

    •  Etoposide  (VP-16,VePe-sid):

      • Monocytic leukemia

      • Testicular cancer

      • Small cell lung carcinoma

    •  Teniposide (Vumon): lymphomas

  •  Adverse Effects:

    • Nausea

    • Vomiting

    • Alopecia

    • Significant hematopoietic toxicity and lymphoid toxicity

•  Camptothecins (topotecan and irinotecan )

  • Mechanism of action: interfere with activity of topoisomerase I (cuts and religates single stranded DNA. DNA is damaged

  • Clinical Uses:

    • Topotecan: metastatic ovarian cancer -- including cisplatin-resistant forms (as effective as paclitaxel)

    •  Adverse Effects: Topotecan --

      • Primary

        • Neutropenia

        • Thrombocytopenia

        • Anemia

      • Other

        • Nausea

        • Alopecia

    • Irinotecan:  prodrug-metabolized active topoisomerase I inhibitor

      • Used in management of colon and rectal cancer, including tumors not responding to 5-FU

      • Adverse Effects: Irinotecan --

        • Most common: diarrhea

        • Also common: nausea, vomiting

        • Dose limiting adverse effect: myelosuppression

• Taxanes (Paclitaxel (Taxol) and Docetaxel (Taxotere))

  • Paclitaxel (Taxol): derivative of the Western Yew

  • Mitotic spindle inhibitor: enhances tubulin polymerization

  • Clinical Uses:

    • Ovarian

    • Advanced breast cancer

  •  Dose-limiting Adverse Effects:

    • Neutropenia

    • Thrombocytopenia

    • Peripheral neuropathy

  • Docetaxel (Taxotere):Used in advanced breast cancer

    • Adverse Effects:bone marrow suppression

Salmon, S. E. and Sartorelli, A. C. Cancer Chemotherapy, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, p. 881-911.