Vincristine (Oncovin) and vinblastine (Velban) are both produced by the leaves of the periwinkle plant. Despite their structural similarity, there are significant differences between them in regard to clinical usefulness and toxicity.
The vinca alkaloids bind avidly to tubulin, a class of proteins that form the mitotic spindle during cell division. The drugs cause cellular arrest in metaphase during mitosis, and cell division cannot be completed. Although the vinca alkaloids usually have been regarded as phase specific in the cell cycle, some mammalian cells are most vulnerable in the late S-phase.
Resistance to vinca alkaloids has been correlated with a decreased rate of drug uptake or an increased drug efflux from these tumor cells. Cross-resistance usually occurs with anthracyclines, dactinomycin, and podophyllotoxins.
Both vincristine and vinblastine are extensively bound to tissues, and only small amounts of the drug are distributed to the brain or CSF. The plasma disappearance of vinblastine and vinorelbine is triphasic. Similar clinical pharmacokinetics have been noted with vin-cristine and vinorelbine. Biliary excretion is the major route of drug excretion.
Vincristine is an important component of the curative combination chemotherapy for acute lymphoblas-tic leukemia, Hodgkin's disease (the MOPP regimen), and non-Hodgkin's lymphomas. It is also used in several regimens for pediatric solid tumors, including Wilms' tumor, Ewing's sarcoma, rhabdomyosarcoma, and neu-roblastoma; in adult tumors of the breast, lung, and cervix; and in sarcomas. Its relative lack of myelosup-pression makes it more attractive than vinblastine for use in combination with myelotoxic drugs. Vinblastine is especially useful in testicular carcinomas and is also active in Hodgkin's disease, other types of lymphomas, breast cancer, and renal cell carcinoma.
Vinorelbine is particularly useful in the treatment of advanced non-small cell lung cancer and can be administered alone or in combination with cisplatin. It is thought to interfere with mitosis in dividing cells through a relatively specific action on mitotic microtubules.
Neurological toxicity is the major dose-limiting tox-icity of vincristine, whereas bone marrow toxicity is limiting for vinblastine. Severe neutropenia occurs in approximately half of the patients receiving vinorelbine. Severe leukopenia is the major side effect of vinblas-tine. These drugs are potent local blistering agents and will produce tissue necrosis if extravasated.
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