Vincristine (Oncovin

Vincristine

Vincristine
Systematic (IUPAC) name
methyl (1R,9R,10S,11R,12R,19R)-11-(acetyloxy)-12-ethyl-4-

[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-

diazatetracyclo[13.3.1.0 4,12.05,10]nonadeca-4(12),5,7,9-tetraen-13-yl]-8-

formyl-10-hydroxy-5-methoxy-8, 16-diazapentacyclo[10.6.1.01,9.02,7.

016,19]nonadeca-2,4,6,13-tetraene-10-carboxylate

Identifiers
CAS number 57-22-7
ATC code L01CA02
PubChem 5978
DrugBank APRD00495
ChemSpider 5758
Chemical data
Formula C46H56N4O10
Mol. mass 824.958 g/mol
Pharmacokinetic data
Bioavailability n/a
Protein binding ~75%
Metabolism Hepatic
Half life 19 to 155 hours
Excretion Mostly biliary, 10% in
urine
Therapeutic considerations
Pregnancy cat. D(AU) D(US)

Legal status ℞ Prescription only

Routes Exclusively intravenous

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 in cancer chemotherapy.
Mode of action
Tubulin is a structural protein which polymerizes 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). It is used in combination with prednisone to
treat childhood leukemia.
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] 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.[3]
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.[4]
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.

Vincristine is one of the older chemotherapy drugs which has been around
for many years. When prepared for use, it becomes a clear and colorless
liquid and is given by intravenous route only. It is most commonly used in
treatment of the following cancers:

• Lymphomas

• Hodgkin's Disease
 • Breast cancer

• Acute Lymphocytic Leukemia

• Soft tissue sarcomas

• Multiple Myeloma

• Neuroblastoma

The type and extent of a cancer will determine the method and schedule of
administration of this drug. This decision is made by the medical oncologist.
Vincristine is normally given once a week.

Side effects:

The degree and severity of the side effects depend on the amount and
schedule of the administration of Vincristine. Following are some of the most
common and important ill effects:

• Low platelet count

• Anemia

• Hair Loss

• Bowel paralysis

• Diarrhea

• Nerve damage

• Damage to the veins, It can cause redness and irritation at the site of
injection, despite proper injection.

• Severe damage to the tissues, if leaks from the injection site

(Extravasation)

It is imperative that patients would relay any side effects or problems to

their medical oncologist.