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Vincristine, also known as leurocristine and sold under the brand name Oncovin among others, is a
chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
medication used to treat a number of types of
cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
. This includes
acute lymphocytic leukemia Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or brui ...
,
acute myeloid leukemia Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with haematopoiesis, normal blood cell production. Sympt ...
,
Hodgkin lymphoma Hodgkin lymphoma (HL) is a type of lymphoma in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the lymph nodes. The condition was named a ...
,
neuroblastoma Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the head, neck, chest, abdomen, or Vertebral column, spine. Symptoms may include ...
, and
small cell lung cancer Small-cell carcinoma, also known as oat cell carcinoma, is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tr ...
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
neuropathic pain Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuo ...
, lung damage, or
low white blood cells Leukopenia () is a decrease in the number of white blood cells (leukocytes). It places individuals at increased risk of infection as white blood cells are the body's primary defense against infections. Signs and symptoms Symptoms may include: * sk ...
which increases the risk of infection. Use during
pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...
may result in
birth defects A birth defect is an abnormal condition that is present at birth, regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can range from mild to severe. Birth de ...
. It works by stopping cells from dividing properly. It is vital that it not be given
intrathecally Intrathecal administration is a route of administration for drugs via an injection into the spinal canal, or into the subarachnoid space (sin. ''intrathecal space'') so that it reaches the cerebrospinal fluid (CSF). It is useful in several appl ...
, as this may kill. Vincristine was first isolated in 1961. It is on the
World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...
. It is a
vinca alkaloid ''Vinca'' alkaloids are a set of Antimitotic agent, anti-mitotic and Anti-microtubule activity, anti-microtubule alkaloid agents originally derived from the periwinkle plant ''Catharanthus roseus'' (basionym ''Vinca rosea'') and other ''vinca'' p ...
that can be obtained from the Madagascar periwinkle ''
Catharanthus roseus ''Catharanthus roseus'', commonly known as bright eyes, Cape periwinkle, graveyard plant, Madagascar periwinkle, old maid, pink periwinkle, rose periwinkle, is a perennial species of flowering plant in the family Apocynaceae. It is native and en ...
''.


Medical uses

Vincristine is delivered via
intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...
infusion Infusion is the process of extracting chemical compounds or flavors from plant material in a solvent such as water, oil or alcohol, by allowing the material to remain suspended in the solvent over time (a process often called steeping). An inf ...
for use in various types of
chemotherapy regimens A chemotherapy regimen is a regimen for chemotherapy, defining the drugs to be used, their dosage, the frequency and duration of treatments, and other considerations. In modern oncology, many regimens combine several chemotherapy drugs in combinat ...
. Its main uses are in non-Hodgkin
lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...
as part of the chemotherapy regimen CHOP R-CVP,
Hodgkin lymphoma Hodgkin lymphoma (HL) is a type of lymphoma in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the lymph nodes. The condition was named a ...
as part of MOPP, COPP, BEACOPP, or the less popular
Stanford V Leland Stanford Junior University, commonly referred to as Stanford University, is a Private university, private research university in Stanford, California, United States. It was founded in 1885 by railroad magnate Leland Stanford (the eighth ...
chemotherapy regimen in
acute lymphoblastic leukemia Acute lymphoblastic leukemia (ALL) is a cancer of the Lymphocyte, lymphoid line of blood cells characterized by the development of large numbers of lymphoblast, immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, ...
(ALL), and in treatment for
nephroblastoma Wilms' tumor or Wilms tumor, also known as nephroblastoma, is a cancer of the kidneys that typically occurs in children (rarely in adults), and occurs most commonly as a renal tumor in child patients. It is named after Max Wilms, the German surg ...
as well as the chemotherapy regimen VDC-IE for Ewing's sarcoma. It is also used to induce remission in ALL with
dexamethasone Dexamethasone is a fluorinated glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive pulmonary disease (COPD), croup, brain swelling, eye pain following eye su ...
and L-
asparaginase Asparaginase is an enzyme that is used as a medication and in food manufacturing. As a medication, L-asparaginase is used to treat acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). It is given by intravenous, injection into ...
, and in combination with
prednisone Prednisone is a glucocorticoid medication mostly used to immunosuppressive drug, suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium ...
to treat childhood leukemia. Vincristine is occasionally used as an
immunosuppressant Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system. Classification Immunosuppressive drugs can be classified ...
, for example, in treating
thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura (TTP) is a blood disorder that results in thrombi, blood clots forming in small blood vessels throughout the body. This results in a thrombocytopenia, low platelet count, hemolytic anemia, low red blood cells d ...
(TTP) or chronic
idiopathic thrombocytopenic purpura Immune thrombocytopenic purpura (ITP), also known as idiopathic thrombocytopenic purpura or immune thrombocytopenia, is an Autoimmunity, autoimmune primary disorder of hemostasis characterized by a low platelet count in the absence of other cause ...
(ITP).


Side effects

The main side effects of vincristine are
chemotherapy-induced peripheral neuropathy Chemotherapy-induced peripheral neuropathy (CIPN) is a nerve-damaging side effect of antineoplastic agents in the common cancer treatment, chemotherapy. CIPN afflicts between 30% and 40% of patients undergoing chemotherapy. Antineoplastic agents ...
,
hyponatremia Hyponatremia or hyponatraemia is a low concentration of sodium in the Serum (blood), blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symp ...
,
constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The Human feces, stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the ...
, and
hair loss Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarring ...
. 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
foot drop Foot drop is a gait abnormality in which the dropping of the forefoot happens out of weakness, irritation or damage to the deep fibular nerve (deep peroneal), including the sciatic nerve, or paralysis of the muscles in the anterior portion of th ...
: 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
anakinra Anakinra, sold under the brand name Kineret, is a biopharmaceutical medication used to treat rheumatoid arthritis, cryopyrin-associated periodic syndromes, familial Mediterranean fever, and Still's disease. It is a slightly modified recombin ...
can reduce the neuropathy. Accidental injection of vinca alkaloids into the spinal canal (
intrathecal Intrathecal administration is a route of administration for drugs via an injection into the spinal canal, or into the subarachnoid space (sin. ''intrathecal space'') so that it reaches the cerebrospinal fluid (CSF). It is useful in several applic ...
administration) is highly dangerous, with a mortality rate approaching 100 percent. The medical literature documents cases of ascending
paralysis Paralysis (: paralyses; also known as plegia) is a loss of Motor skill, motor function in one or more Skeletal muscle, muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory d ...
due to massive
encephalopathy Encephalopathy (; ) means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of overall brain dysfunction; this syndrome ...
and spinal nerve
demyelination A demyelinating disease refers to any disease affecting the nervous system where the myelin sheath surrounding neurons is damaged. This damage disrupts the transmission of signals through the affected nerves, resulting in a decrease in their con ...
, 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 Cerebrospinal fluid (CSF) is a clear, colorless Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ven ...
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
China China, officially the People's Republic of China (PRC), is a country in East Asia. With population of China, a population exceeding 1.4 billion, it is the list of countries by population (United Nations), second-most populous country after ...
in 2007 when batches of
cytarabine Cytarabine, also known as cytosine arabinoside (ara-C), is a chemotherapy medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and non-Hodgkin's lymphoma. It is given b ...
and
methotrexate Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immunosuppressive drug, immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy, ectopic pregnancies. Types of cancers it is u ...
(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
drug resistance Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in treating a disease or condition. The term is used in the context of resistance that pathogens or cancers have "acquired", that is ...
by overexpression of the
p-glycoprotein P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein ...
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
tubulin Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytosk ...
protein, stopping the tubulin dimers from polymerizing to form microtubules, causing the cell to be unable to separate its
chromosome A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...
s during the
metaphase Metaphase ( and ) is a stage of mitosis in the eukaryotic cell cycle in which chromosomes are at their second-most condensed and coiled stage (they are at their most condensed in anaphase). These chromosomes, carrying genetic information, alig ...
. The cell then undergoes
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
. The vincristine molecule inhibits
leukocyte White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
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
vindoline Vindoline is a chemical precursor to vinblastine. Vindoline is formed through biosynthesis from Tabersonine. See also * Lochnericine * Dimerization of catharanthine and vindoline Catharanthine and vindoline are terpenoid indole alkaloids ...
and
catharanthine Catharanthine is a terpene indole alkaloid produced by the medicinal plant '' Catharanthus roseus'' and '' Tabernaemontana divaricata''. Catharanthine is derived from strictosidine, but the exact mechanism by which this happens is currently unkn ...
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
liposome A liposome is a small artificial vesicle, spherical in shape, having at least one lipid bilayer. Due to their hydrophobicity and/or hydrophilicity, biocompatibility, particle size and many other properties, liposomes can be used as drug deliver ...
encapsulation of vincristine enhances the efficacy of the vincristine drug while simultaneously decreasing the
neurotoxicity Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifical ...
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.


History

Having been used as a folk remedy for centuries, studies in the 1950s revealed that the rosy periwinkle ''
Catharanthus roseus ''Catharanthus roseus'', commonly known as bright eyes, Cape periwinkle, graveyard plant, Madagascar periwinkle, old maid, pink periwinkle, rose periwinkle, is a perennial species of flowering plant in the family Apocynaceae. It is native and en ...
'' contained over 120 alkaloids, many of which are biologically active, the two most significant being vincristine and
vinblastine Vinblastine, sold under the brand name Velban among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. This includes Hodgkin's lymphoma, non-small-cell lung cancer, bladder canc ...
. Its use as an anti-tumor, anti-mutagenic agent is well documented in the ancient
Ayurveda Ayurveda (; ) is an alternative medicine system with historical roots in the Indian subcontinent. It is heavily practised throughout India and Nepal, where as much as 80% of the population report using ayurveda. The theory and practice of ayur ...
system of medicine and in the folk culture of
Madagascar Madagascar, officially the Republic of Madagascar, is an island country that includes the island of Madagascar and numerous smaller peripheral islands. Lying off the southeastern coast of Africa, it is the world's List of islands by area, f ...
and
Southern Africa Southern Africa is the southernmost region of Africa. No definition is agreed upon, but some groupings include the United Nations geoscheme for Africa, United Nations geoscheme, the intergovernmental Southern African Development Community, and ...
. It was not found to be anti-diabetic in double blinded controlled studies. While initial studies for its use in
diabetes mellitus Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or th ...
were disappointing, the discovery that it caused
myelosuppression Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting ( ...
(decreased activity of the bone marrow) led to its study in mice with
leukemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...
, whose lifespan was prolonged by the use of a vinca preparation. Treatment of the ground plant with Skellysolve-B (hexane), followed by dilute
tartaric acid Tartaric acid is a white, crystalline organic acid that occurs naturally in many fruits, most notably in grapes but also in tamarinds, bananas, avocados, and citrus. Its salt (chemistry), salt, potassium bitartrate, commonly known as cream of ta ...
and
benzene Benzene is an Organic compound, organic chemical compound with the Chemical formula#Molecular formula, molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar hexagonal Ring (chemistry), ring with one hyd ...
extraction, provided an active fraction. This fraction was further chromatographed on deactivated
aluminium oxide Aluminium oxide (or aluminium(III) oxide) is a chemical compound of aluminium and oxygen with the chemical formula . It is the most commonly occurring of several Aluminium oxide (compounds), aluminium oxides, and specifically identified as alum ...
using
trichloromethane Chloroform, or trichloromethane (often abbreviated as TCM), is an organochloride with the chemical formula, formula and a common solvent. It is a Volatility (chemistry), volatile, colorless, sweet-smelling, dense liquid produced on a large scale ...
and benzene, and separation by pH using extraction with various buffers to yield vincristine. Vincristine was approved by the US
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
(FDA) in July 1963 under the brand name Oncovin and was marketed by
Eli Lilly and Company Eli Lilly and Company, Trade name, doing business as Lilly, is an American multinational Medication, pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 count ...
. The drug was initially developed by a team at Lilly Research Laboratories in
Indianapolis Indianapolis ( ), colloquially known as Indy, is the List of capitals in the United States, capital and List of municipalities in Indiana, most populous city of the U.S. state of Indiana and the county seat of Marion County, Indiana, Marion ...
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
generic drug A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...
makers were suppliers of vincristine in the United States: Teva and
Pfizer Pfizer Inc. ( ) is an American Multinational corporation, multinational Pharmaceutical industry, pharmaceutical and biotechnology corporation headquartered at The Spiral (New York City), The Spiral in Manhattan, New York City. Founded in 184 ...
. 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 pharmaceutical bioprospecting in the fields of
ethnobotany Ethnobotany is an interdisciplinary field at the interface of natural and social sciences that studies the relationships between humans and plants. It focuses on traditional knowledge of how plants are used, managed, and perceived in human socie ...
and
ethnomedicine Ethnomedicine is a study or comparison of the traditional medicine based on bioactive compounds in plants and animals and practiced by various ethnic groups, especially those with little access to western medicines, e.g., indigenous peoples. The ...
. Some consider the ''
Catharanthus roseus ''Catharanthus roseus'', commonly known as bright eyes, Cape periwinkle, graveyard plant, Madagascar periwinkle, old maid, pink periwinkle, rose periwinkle, is a perennial species of flowering plant in the family Apocynaceae. It is native and en ...
'' plant from which vincristine is derived, and its
folk remedies Traditional medicine (also known as indigenous medicine or folk medicine) refers to the knowledge, skills, and practices rooted in the cultural beliefs of various societies, especially Indigenous groups, used for maintaining health and treatin ...
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 The Industrial Revolution, sometimes divided into the First Industrial Revolution and Second Industrial Revolution, was a transitional period of the global economy toward more widespread, efficient and stable manufacturing processes, succee ...
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 The Chelsea Physic Garden was established as the Apothecaries' Garden in London, England, in 1673 by the Worshipful Society of Apothecaries to grow plants to be used as medicines. This four acre physic garden, the term here referring to the scie ...
from the
Jardin des plantes The Jardin des Plantes (, ), also known as the Jardin des Plantes de Paris () when distinguished from other ''jardins des plantes'' in other cities, is the main botanical garden in France. Jardin des Plantes is the official name in the present da ...
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 The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
(FDA) approved a liposomal formulation of vincristine branded as Marqibo. Marqibo was voluntarily withdrawn from the US market in November 2021. A nano-particle bound version of vincristine was under development as of 2014. In 1995 and 2006, Malagasy
agronomists An agriculturist, agriculturalist, agrologist, or agronomist (abbreviated as agr.) is a professional in the science, practice, and management of agriculture and agribusiness. It is a regulated profession in Canada, India, the Philippines, the Uni ...
and American
political ecologists Political ecology is the study of the relationships between political, economic and social factors with environmental issues and changes. Political ecology differs from apolitical ecological studies by politicizing environmental issues and pheno ...
studied the production of ''Catharanthus roseus'' around
Fort Dauphin Fort Dauphin may refer to: ;Canada * Fort Dauphin (Manitoba), in Manitoba * Fort Dauphin (Nova Scotia), in Nova Scotia ;Haiti * Fort-Liberté Fort-Liberté (; ) is a List of communes of Haiti, commune and administrative capital of the Nord-Est ...
and
Ambovombe Ambovombe-Androy , or just Ambovombe, is a city in the far south of Madagascar, and the capital of the Androy region. Ambovombe has now acquired city status with an officially estimated population in 2018 of 114,230. The city is connected by the R ...
and its export as a natural source of the alkaloids used to make vincristine, vinblastine and other
vinca alkaloid ''Vinca'' alkaloids are a set of Antimitotic agent, anti-mitotic and Anti-microtubule activity, anti-microtubule alkaloid agents originally derived from the periwinkle plant ''Catharanthus roseus'' (basionym ''Vinca rosea'') and other ''vinca'' p ...
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.


References

{{Authority control Vinca alkaloids Commercialization of traditional medicines Drugs developed by Eli Lilly and Company Mitotic inhibitors Acetate esters Wikipedia medicine articles ready to translate World Health Organization essential medicines Drugs developed by Pfizer