Vincristine

Chemotherapy drugs are often toxic, and before treatment, it's wise to educate oneself about what possible side effects and toxicities might be experienced as well as to understand its basic pharmacology. Part of the R-hyperCVAD + MTX-Ara-C is "V"incristine, one of the older known drugs in this powerful combination.

Vincristine's formal name is 22-oxovincaleukoblastine, and its formula is C46H56N4O10 with a molar mass of 824.96 g/mole. It is an antineoplastic antitumor alkaloid, now biosynthesized, but originally isolated from Vinca rosea Linn. It has a melting point of 218-220 degrees C, but is in liquid form during intravenous administration. It must not be administered intrathecally as this is fatal; 55 cases have been reported since 1968 of accidental spinal route injection. Once administered, it distributes through rapid, extensive, and reversible tissue binding. Excess will be excreted in the bile and feces, so take care in handling any waste products separately. Vincristine is used specifically to treat leukemias and lymphomas, including mantle-cell lymphoma.

Vincristine is a antimitotic that inhibits mitosis in the metaphase stage, by binding to tubulin, preventing the formation of spindles and thus the transition to telephase. Vincristine also appears to interfere with the ability by the cell to synthesise DNA and RNA. As one can see in the structure above, it is a large molecule with many polar oxygens; these enable its binding to the tubulin. It is also related to several other compounds, listed at http://biotech.icmb.utexas.edu/botany/vvv.html.

Unfortunately, vincristine is known for its severe toxicity. It is teratogenic, carciogenic, and fetotoxic. Side effects include myelosuppression, irritation at the injection site, and neurotoxicities, including peripheral neuropathy. However, this is due to neural tissue distribution in the body, as vincristine does not readily cross the blood-brain barrier (CSF:plasma ratio of 5%). For this reason, persons with demyelinating disorders cannot take vincristine. An extensive list of possible adverse effects can be found at http://www.cancercare.on.ca/pdfdrugs/vincrist.pdf.

In 2006, a study was performed on rats in which one group received a fixed dose of vincristine while another group received an increasing dose with each weekly treatment. At the end of 5 and 19 weeks, both groups exhibited peripheral sensory-motor neuropathy, while the fixed-dose group exhibited more long-term histological and electrophysiological signs of neuropathy. Signs included axonal degeneration with relative demyelination as well as a significant decrease in the amplitude of the sensory nerve action potential and compound muscle action potential in tested nerves. However, encouragingly, after discontinuation (at 14 weeks), both groups exhibited lesser number of fibers with axonal and myelin lesions, so there is an expectation that a normal rat should exhibit improvement of electrophysiological and histological changes even after vincristine treatment. The rat has been considered a viable model for human physiology, so a patient being treated with intravenous R-hyperVCAD should not expect vincristine to be fatal or experienced neuropathy to persist at identical levels after treatment ends.