Vincristine

Vincristine (Oncovin®) is an alkaloid from the Madagascar periwinkle (Catharanthus roseus, formerly Vinca rosea and hence its name). It is used in chemotherapy.

Mode of action

Tubulin is a structural protein which polymerises to form microtubules. The cell cytoskeleton and mitotic spindle, amongst other things, are made of microtubules. Vincristine binds to tubulin dimers causing disassembly of microtubule structures. Disruption of the microtubules arrests mitosis in metaphase. The vinca alkaloids therefore affect all rapidly dividing cell types, including cancer cells but also as intestinal epithelium and bone marrow.

Side effects

The main side-effects of vincristine are peripheral neuropathy and constipation. The latter may require laxatives, while the former can be a reason to reduce the dose of vincristine.

Accidental injection of vinca alkaloids into the spinal canal (intrathecal administration) is highly dangerous, with a mortality rate approaching 100%. The medical literature documents cases of ascending paralysis due to massive encephalopathy and spinal nerve demyelination, accompanied by intractable pain, almost uniformly leading to death; a handful of survivors were left with devastating neurological damage with no hope of recovery.

Uses

Vincristine, injected intravenously only, is used in various types of chemotherapy regimens. Its main uses are in non Hodgkin's lymphoma as part of the chemotherapy regimen CHOP, Hodgkin's lymphoma as part of the Stanford V chemotherapy regimen, and in acute lymphoblastic leukaemia.

History

Having been used as a folk remedy for centuries, studies in the 1950s revealed that C. roseus contained 70 alkaloids, many of which biologically active. Vincristine was approved by the United States Food and Drug Administration (FDA) in July 1963 as Oncovin. The drug was initially marketed by Eli Lilly and Company.

Suppliers

Three generic drug makers supply vincristine in the United States - APP, Mayne, and Sicor.

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