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Vincristine, also known as leurocristine and sold under the brand name Oncovin among others, is a medication used to treat a number of types of . This includes acute lymphocytic leukemia, acute myeloid leukemia, , , and small cell lung cancer among others. It is given intravenously.

Most people experience some side effects from vincristine treatment. Commonly it causes a change in sensation, hair loss, constipation, difficulty walking, and headaches. Serious side effects may include , lung damage, or which increases the risk of infection. Use during may result in . It works by stopping cells from dividing properly. It is vital that it not be given intrathecally, as this may kill.

Vincristine was first isolated in 1961.

(2025). 9783527326693, Wiley-VCH. .
It is on the World Health Organization's List of Essential Medicines. It is a that can be obtained from the Madagascar periwinkle Catharanthus roseus.


Medical uses
Vincristine is delivered via infusion for use in various types of chemotherapy regimens. Its main uses are in non-Hodgkin as part of the chemotherapy regimen CHOP R-CVP, as part of MOPP, COPP, BEACOPP, or the less popular chemotherapy regimen in acute lymphoblastic leukemia (ALL), and in treatment for as well as the chemotherapy regimen VDC-IE for Ewing's sarcoma. It is also used to induce remission in ALL with and L-, and in combination with to treat childhood leukemia. 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 chemotherapy-induced peripheral neuropathy, , , and .

Vincristine-induced neuropathy is the main dose-limiting side effect. Chemotherapy-induced peripheral neuropathy can be severe, and may be a reason to reduce or avoid using vincristine. The symptoms are progressive and enduring tingling numbness, pain and hypersensitivity to cold, beginning in the hands and feet and sometimes affecting the arms and legs. One of the first symptoms of peripheral neuropathy is : A person with a family history of foot drop and/or Charcot-Marie-Tooth disease (CMT) should avoid vincristine. A 2021 study has suggested that can reduce the neuropathy.

Accidental injection of vinca alkaloids into the spinal canal ( administration) is highly dangerous, with a mortality rate approaching 100 percent. The medical literature documents cases of ascending due to massive and spinal nerve , accompanied by intractable pain, almost uniformly leading to death. Several patients have survived after aggressive and immediate intervention. Rescue treatments consist of washout of the cerebrospinal fluid and administration of protective medications. Children may do better following this injury. One child, who was aggressively treated at the time of the injection, recovered almost completely with only mild neurological deficits. A significant series of inadvertent intrathecal vincristine administration occurred in in 2007 when batches of and (both often used intrathecally) manufactured by the company Shanghai Hualian were found to be contaminated with vincristine.

The overuse of vincristine may also lead to by overexpression of the pump (Pgp). There is an attempt to overcome resistance by the addition of derivatives and substituents to the vincristine molecule.


Mechanism of action
Vincristine works partly by binding to the protein, stopping the tubulin dimers from polymerizing to form microtubules, causing the cell to be unable to separate its during the .
(2015). 9780444626493, Elsevier.
The cell then undergoes . The vincristine molecule inhibits production and maturation. A downside, however, to vincristine is that it does not only affect the division of cancer cells. It affects all rapidly dividing cell types, making it necessary for the very specific administration of the drug.


Chemistry
The natural extraction of vincristine from Catharanthus roseus is produced at a percent yield of less than 0.0003%. For this reason, alternate methods to produce synthetic vincristine are being used. Vincristine is created through the semi-synthesis coupling of indole alkaloids and in the vinca plant. It can also now be synthesized through a stereocontrolled total synthesis technique which retains the correct stereochemistry at C18' and C2'. The absolute stereochemistry at these carbons is responsible for vincristine's anticancer activity.

The encapsulation of vincristine enhances the efficacy of the vincristine drug while simultaneously decreasing the associated with it. Liposome encapsulation increases vincristine's plasma concentration and circulation lifetime in the body, and allows the drug to enter cells more easily.

(2025). 9780121827960


History
Having been used as a folk remedy for centuries, studies in the 1950s revealed that the rosy periwinkle Catharanthus roseus contained over 120 alkaloids, many of which are biologically active, the two most significant being vincristine and . Its use as an anti-tumor, anti-mutagenic agent is well documented in the ancient system of medicine and in the folk culture of and . It was not found to be anti-diabetic in double blinded controlled studies. While initial studies for its use in diabetes mellitus were disappointing, the discovery that it caused (decreased activity of the bone marrow) led to its study in mice with , whose lifespan was prolonged by the use of a vinca preparation. Treatment of the ground plant with (hexane), followed by dilute and extraction, provided an active fraction. This fraction was further on deactivated using and benzene, and separation by pH using extraction with various buffers to yield vincristine.

Vincristine was approved by the US Food and Drug Administration (FDA) in July 1963 under the brand name Oncovin and was marketed by Eli Lilly and Company. The drug was initially developed by a team at Lilly Research Laboratories in where it was demonstrated that vincristine cured artificially induced leukemia in mice and remission of acute leukemias of childhood.

Production of vincristine required one ton of dried periwinkle leaves to produce one ounce of vincristine. The periwinkle was grown on a ranch in Texas.


Society and culture

Suppliers
Two makers were suppliers of vincristine in the United States: Teva and . In 2019 Teva stopped producing vincristine, leaving Pfizer as the only company in production. Teva has said that they will restart production, and expect it to be available in 2020.


Shortage
In October 2019 an impending shortage was reported; no adequate substitute is known for treating childhood cancers. By 2022, the shortage of vincristine continued.


Controversy

Pharmaceutical bioprospecting
Vincristine's origins are debated as an example of in the fields of and . Some consider the Catharanthus roseus plant from which vincristine is derived, and its to be endemic to Madagascar, and that Madagascar was denied royalties from vincristine sales. However, Catharanthus roseus has a documented history in folk medicine treatments in other locations. In 1963, Lilly researchers acknowledged that the plant was used in Brazil to treat hemorrhage, scurvy, toothaches, and chronic wounds; in the British West Indies to treat diabetic ulcers; and in the Philippines and South Africa as an oral hypoglycemic agent – but not as a treatment for cancer.

Catharanthus roseus has been a cosmopolitan species since before the Industrial Revolution and the plant's use in folk remedies suggested general bioactivity for diabetes treatment, not cancer. In the mid-eighteenth century, botanist Judith Sumner recorded the arrival of Catharanthus roseus at London's Chelsea Physic Garden from the Jardin des plantes in Paris. It's unclear how the plant first arrived in Paris and the details of its origins in Madagascar beyond reports of its transport from Madagascar by early European explorers. Vincristine was initially distributed at cost to increase accessibility, though later switched to a for-profit model to recover the costs of production and development. According to Michael Brown, vincristine may not be a tidy example of pharmaceutical bioprospecting, but it demonstrates how pharmaceuticals with a history of use in folk medicine have intellectual property claims which are difficult to untangle.


Vincristine and confusion with other drugs in administration
Vincristine has been involved in a number of medical errors. Multiple instances of vincristine having been administered improperly, after having been confused with other drugs, have occurred. If delivered into the spine (intrathecal) it causes paralysis and usually death.

In 2003, two Australian oncology pharmacists recommended a solution. The suggested procedure is to prepare and administer vincristine in a small volume mini-bag rather than a syringe thus physically preventing the vincristine syringe being accidentally attached to a spinal needle. Acceptance of this safer procedure has been slow.


Research
In 2012, the US Food and Drug Administration (FDA) approved a liposomal formulation of vincristine branded as Marqibo. FDA press release Aug 9, 2012 Marqibo was voluntarily withdrawn from the US market in November 2021.

A nano-particle bound version of vincristine was under development as of 2014. Bind Therapeutics conference call of Nov 6, 2014

In 1995 and 2006, Malagasy and American political ecologists studied the production of Catharanthus roseus around Fort Dauphin and and its export as a natural source of the alkaloids used to make vincristine, vinblastine and other cancer drugs. Their research focused on the wild collection of periwinkle roots and leaves from roadsides and fields and its industrial cultivation on large farms.

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