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Mitotic Inhibitors


The vinca alkaloids are large, complex molecules derived from the periwinkle plant. Binding to tubulin, the major component of cellular microtubules, accounts for the antineoplastic effects of these drugs. Vinca alkaloids inhibit microtubule polymerization and increase microtubule disassembly. The mitotic spindle apparatus is disrupted, and segregation of chromosomes in metaphase is arrested. These effects account for the primary M-phase action of vinca alkaloids, although other antitubulin effects related to cytoskeletal maintenance and protein trafficking may be seen. The 2 drugs of importance in this class are vincristine and vinblastine. Both are given IV, and both cause severe local vesication if injected perivascularly. Drug extravasation may cause severe tissue reactions and lead to self-trauma. The vinca alkaloids are metabolized primarily in the liver but may be partially excreted in an unchanged form in the urine. Although vinca alkaloids are related structurally, resistance to one does not imply resistance to all drugs in this category. Vincristine use is limited by neurologic toxicity that may include a slowly reversible sensorimotor peripheral neuropathy and muscle weakness. In comparison, the dose-limiting toxicity associated with vinblastine is related to myelosuppression and leukopenia; neurologic toxicity develops only at high doses.

Vinorelbine is a second generation semisynthetic vinca alkaloid that is derived from vinblastine but with broader anti-tumor efficacy. According to recent studies in the veterinary literature, this drug may have efficacy in canine primary lung and cutaneous mast cell tumors.

Paclitaxel and docetaxel are antimicrotubule agents extracted from the Pacific and European yew trees, respectively. Taxanes bind to tubulin subunits, enhance microtubule polymerization, and inhibit microtubule depolymerization. Formation of stable microtubule bundles disrupts tubulin equilibrium and blocks normal progression through the cell cycle. These agents are actively used in human medicine and may be useful in treating metastatic osteosarcoma and mammary carcinoma in veterinary medicine. Myelosuppression, anaphylactoid reactions (probably related to the drug vehicle, Cremophor EL), and GI effects (diarrhea, mucosal ulceration, and emesis) have been reported in dogs treated with paclitaxel.

Last full review/revision March 2012 by Deborah T. Kochevar, DVM, PhD, DACVCP; Lisa G. Barber, DVM, DACVIM (Oncology); Kristine E. Burgess, DVM, DACVIM (Oncology)

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