Vincristine

Vincristine (brand name, Oncovin), also known as leurocristine, is a vinca alkaloid from the Madagascar periwinkle (Catharanthus roseus, formerly Vinca rosea and hence its name). It is a mitotic inhibitor, and is used in cancer chemotherapy.

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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, inhibiting assembly 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 intestinal epithelium and bone marrow.

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 MOPP or COPP, or the less popular Stanford V chemotherapy regimen, and in acute lymphoblastic leukemia. It is occasionally used as an immunosuppressant, e.g. in thrombotic thrombocytopenic purpura (TTP).

Side effects

The main side-effects of vincristine are peripheral neuropathy, hyponatremia, constipation and hair loss.

Peripheral neuropathy can be severe, and hence a reason to avoid, reduce, or stop the use of vincristine. One of the first symptoms of peripheral neuropathy is foot drop: a person with a family history of foot drop and/or Charcot-Marie-Tooth disease (CMT) may benefit from genetic testing for CMT before taking vincristine.^[1]

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. Rescue treatments consist of washout of the cerebrospinal fluid and administration of protective medications.^[2]

History

Having been used as a folk remedy for centuries, studies in the 1950s revealed that C. roseus contained 70 alkaloids, many of which are biologically active. While initial studies for its use in diabetes mellitus were disappointing, the discovery that it caused myelosuppression (decreased activity of the bone marrow) led to its study in mice with leukemia, whose lifespan was prolonged by the use of a vinca preparation. Treatment of the ground plant with Skelly-B defatting agent and an acid benzene extract led to a fraction termed "fraction A". This fraction was further treated with aluminium oxide, chromatography, trichloromethane, benz-dichloromethane and separation by pH to yield vincristine.^[3]

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 (Teva).

See also

• Rosy Periwinkle

References

1. ^ Graf WD, Chance PF, Lensch MW, Eng LJ, Lipe HP, Bird TD (1996). "Severe vincristine neuropathy in Charcot-Marie-Tooth disease type 1A". Cancer 77 (7): 1356–62. doi:10.1002/(SICI)1097-0142(19960401)77:7%3C1356::AID-CNCR20%3E3.0.CO;2-%23. PMID 8608515.
2. ^ Qweider M, Gilsbach JM, Rohde V (2007). "Inadvertent intrathecal vincristine administration: a neurosurgical emergency. Case report". J Neurosurg Spine 6 (3): 280–3. PMID 17355029.
3. ^ Johnson IS, Armstrong JG, Gorman M, Burnett JP (1963). "The vinca alkaloids: a new class of oncolytic agents". Cancer Res 23: 1390-427. PMID 14070392.