Vinorelbine (NVB), sold under the brand name Navelbine among others, is a

chemotherapy medication Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothera ...

used to treat a number of types of cancer. This includes

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a r ...

and

non-small cell lung cancer Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to s ...

. It is given by

injection into a vein 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 nutri ...

or by mouth. Common side effects include

bone marrow suppression 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 ...

, pain at the site of injection, vomiting, feeling tired, numbness, and diarrhea. Other serious side effects include

shortness of breath Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing di ...

. Use during

pregnancy Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...

may harm the baby. Vinorelbine is in the

vinca alkaloid ''Vinca'' alkaloids are a set of anti-mitotic and anti-microtubule alkaloid agents originally derived from the periwinkle plant ''Catharanthus roseus'' (basionym ''Vinca rosea'') and other ''vinca'' plants. They block beta-tubulin polymerizati ...

family of medications. It is believed to work by disrupting the normal function of

microtubules Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 a ...

and thereby stopping

cell division Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there ar ...

. Vinorelbine was approved for medical use in the United States in 1994. 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 ...

Medical uses

Vinorelbine is approved for the treatment of non-small-cell lung cancer. It is used off-label for other cancers such as

metastatic breast cancer Metastatic breast cancer, also referred to as metastases, advanced breast cancer, secondary tumors, secondaries or stage IV breast cancer, is a stage of breast cancer where the breast cancer cells have spread to distant sites beyond the axillary l ...

. It is also active in

rhabdomyosarcoma Rhabdomyosarcoma (RMS) is a highly aggressive form of cancer that develops from mesenchymal cells that have failed to fully differentiate into myocytes of skeletal muscle. Cells of the tumor are identified as rhabdomyoblasts. There are four subt ...

Side effects

Vinorelbine has a number of side-effects that can limit its use:

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 ...

(a progressive, enduring and often irreversible tingling numbness, intense pain, and hypersensitivity to cold, beginning in the hands and feet and sometimes involving the arms and legs), lowered resistance to infection, bruising or bleeding,

anaemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...

, vomitings,

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

, tiredness and a general feeling of weakness (

asthenia Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...

), inflammation of the vein into which it was injected (

phlebitis Phlebitis (or Venitis) is inflammation of a vein, usually in the legs. It most commonly occurs in superficial veins. Phlebitis often occurs in conjunction with thrombosis and is then called thrombophlebitis or superficial thrombophlebitis. Unlike ...

). Seldom severe

hyponatremia Hyponatremia or hyponatraemia is a low concentration of sodium in the 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. Symptoms can be a ...

is seen. Less common effects are hair loss and allergic reaction.

Pharmacology

The antitumor activity is due to inhibition of mitosis through interaction with tubulin.

History

Vinorelbine was invented by the pharmacist Pierre Potier and his team from the CNRS in

France France (), officially the French Republic ( ), is a country primarily located in Western Europe. It also comprises of overseas regions and territories in the Americas and the Atlantic, Pacific and Indian Oceans. Its metropolitan area ...

in the 1980s and was licensed to the oncology department of the Pierre Fabre Group. The drug was approved in France in 1989 under the brand name Navelbine for the treatment of non-small cell

lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. Lung carcinomas derive from transformed, malign ...

. It gained approval to treat

in 1991. Vinorelbine received approval by the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...

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 respon ...

(FDA) in December 1994 sponsored by Burroughs Wellcome Company. Pierre Fabre Group now markets Navelbine in the U.S., where the drug went generic in February 2003. In most European countries, vinorelbine is approved to treat non-small cell lung cancer and breast cancer. In the United States it is approved only for non-small cell lung cancer.

Sources

The Madagascan periwinkle ''

Catharanthus roseus ''Catharanthus roseus'', commonly known as bright eyes, Cape periwinkle, graveyard plant, Madagascar periwinkle, old maid, pink periwinkle, rose periwinkle, is a species of flowering plant in the family Apocynaceae. It is native and endemic to M ...

'' L. is the source for a number of important natural products, including catharanthine and vindoline and the

s it produces from them: leurosine and the

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...

agents

vinblastine Vinblastine (VBL), 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 ca ...

and

vincristine Vincristine, also known as leurocristine and marketed under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer. This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin's ...

, all of which can be obtained from the plant. The newer

semi-synthetic Semisynthesis, or partial chemical synthesis, is a type of chemical synthesis that uses chemical compounds isolated from natural sources (such as microbial cell cultures or plant material) as the starting materials to produce novel compounds with ...

chemotherapeutic agent vinorelbine, which is used in the treatment of

non-small-cell lung cancer Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to s ...

and is not known to occur naturally. However, it can be prepared either from vindoline and catharanthine or from leurosine, in both cases by synthesis of

anhydrovinblastine Vinorelbine (NVB), sold under the brand name Navelbine among others, is a chemotherapy medication used to treat a number of types of cancer. This includes breast cancer and non-small cell lung cancer. It is given by injection into a vein or by mou ...

. The leurosine pathway uses the

Nugent–RajanBabu reagent Bis(cyclopentadienyl)titanium(III) chloride, also known as the Nugent–RajanBabu reagent, is the organotitanium compound which exists as a dimer with the formula C5H5)2TiClsub>2. It is an air sensitive green solid. The complex finds specializ ...

in a highly chemoselective de-oxygenation of leurosine. Anhydrovinblastine is then reacted sequentially with ''N''-bromosuccinimide and

trifluoroacetic acid Trifluoroacetic acid (TFA) is an organofluorine compound with the chemical formula CF3CO2H. It is a structural analogue of acetic acid with all three of the acetyl group's hydrogen atoms replaced by fluorine atoms and is a colorless liquid with ...

followed by

silver tetrafluoroborate Silver tetrafluoroborate is an inorganic compound with the chemical formula AgBF4. It is a white solid that dissolves in polar organic solvents as well as water. In its solid state, the Ag+ centers are bound to fluoride. Preparation Silver tetraf ...

to yield vinorelbine. Vinorelbine from leurosine and from catharanthine plus vindoline

Oral formulation

An oral formulation has been marketed and registered in most European countries. It has similar efficacy as the intravenous formulation, but it avoids venous toxicities of an infusion and is easier to take. The oral form is not approved in the United States, or Australia.

References

External links

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