Vincristine

Vincristine (brand name, Oncovin), also known as leurocristine, is a vinca alkaloid from the Catharanthus roseus (Madagascar periwinkle), formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used as a antineoplastic drug in cancer 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, 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 is delivered via intravenous infusion for use 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, COPP, BEACOPP, or the less popular Stanford V chemotherapy regimen, in acute lymphoblastic leukemia, and in treatment for nephroblastoma (Wilms tumor, a kidney tumor common in children). Vincristine is occasionally used as an immunosuppressant, for example, in treating thrombotic thrombocytopenic purpura (TTP) or chronic idiopathic thrombocytopenic purpura (ITP).

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.

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. A significant series of inadvertent intrathecal vincristine administration occurred in China in 2007 when batches of cytarabine and methotrexate (both often used intrathecally) manufactured by the company Shanghai Hualian were found to be contaminated with vincristine.

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.

Vincristine was approved by the United States Food and Drug Administration (FDA) in July 1963 as Oncovin. The drug was initially discovered by a team lead by Dr. J.G. Armstrong; it was then marketed by Eli Lilly and Company.

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