Vinorelbine

Last updated
Vinorelbine
Vinorelbine.svg
Vinorelbine ball-and-stick.png
Clinical data
Trade names Navelbine
AHFS/Drugs.com Monograph
MedlinePlus a695013
Pregnancy
category
  • AU:D
Routes of
administration 		intravenous, by mouth [1]
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 43 ± 14% (oral) [2]
Protein binding 79 to 91%
Metabolism liver (CYP3A4-mediated)
Elimination half-life 27.7 to 43.6 hours
Excretion Fecal (46%) and kidney (18%)
Identifiers
  • Methyl (2β,3β,4β,5α,12β,19α)-4-acetoxy-15-[(12S,14R)-16-ethyl-12-(methoxycarbonyl)-1,10-diazatetracyclo[12.3.1.03,11.04,9]octadeca-3(11),4,6,8,15-pentaen-12-yl]-3-hydroxy-16-methoxy-1-methyl-6,7-didehydroaspidospermidine-3-carboxylate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C45H54N4O8
Molar mass 778.947 g·mol−1
3D model (JSmol)
  • [H][C@]89C=C(CC)CN(Cc1c([nH]c2ccccc12)[C@@](C(=O)OC)(c3cc4c(cc3OC)N(C)[C@@]5([H])[C@@](O)(C(=O)OC)[C@H](OC(C)=O)[C@]7(CC)C=CCN6CC[C@]45[C@@]67[H])C8)C9
  • InChI=1S/C45H54N4O8/c1-8-27-19-28-22-44(40(51)55-6,36-30(25-48(23-27)24-28)29-13-10-11-14-33(29)46-36)32-20-31-34(21-35(32)54-5)47(4)38-43(31)16-18-49-17-12-15-42(9-2,37(43)49)39(57-26(3)50)45(38,53)41(52)56-7/h10-15,19-21,28,37-39,46,53H,8-9,16-18,22-25H2,1-7H3/t28-,37-,38+,39+,42+,43+,44-,45-/m0/s1 Yes check.svgY
  • Key:GBABOYUKABKIAF-IELIFDKJSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Vinorelbine (NVB), sold under the brand name Navelbine among others, is a chemotherapy medication used to treat a number of types of cancer. [3] This includes breast cancer and non-small cell lung cancer. [3] It is given by injection into a vein or by mouth. [3] [1]

Contents

Common side effects include bone marrow suppression, pain at the site of injection, vomiting, feeling tired, numbness, and diarrhea. [3] Other serious side effects include shortness of breath. [3] Use during pregnancy may harm the baby. [3] Vinorelbine is in the vinca alkaloid family of medications. [1] It is believed to work by disrupting the normal function of microtubules and thereby stopping cell division. [3]

Vinorelbine was approved for medical use in the United States in 1994. [3] It is on the World Health Organization's List of Essential Medicines. [4] [5]

Medical uses

Vinorelbine is approved for the treatment of non-small-cell lung cancer. [6] [7] It is used off-label for other cancers such as metastatic breast cancer. It is also active in rhabdomyosarcoma. [8]

Side effects

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

Chemotherapy-induced peripheral neuropathy (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 [9] ), lowered resistance to infection, bruising or bleeding, anaemia, constipation, vomitings, diarrhea, nausea, tiredness and a general feeling of weakness (asthenia), inflammation of the vein into which it was injected (phlebitis). Seldom severe hyponatremia 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. [10]

History

Vinorelbine was invented by the pharmacist Pierre Potier and his team from the CNRS in France 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. It gained approval to treat metastatic breast cancer in 1991. Vinorelbine received approval by the United States Food and Drug Administration (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 L. is the source for a number of important natural products, including catharanthine and vindoline [11] and the vinca alkaloids it produces from them: leurosine and the chemotherapy agents vinblastine and vincristine, all of which can be obtained from the plant. [12] [13] [6] [14] The newer semi-synthetic chemotherapeutic agent vinorelbine, which is used in the treatment of non-small-cell lung cancer [6] [7] and is not known to occur naturally. However, it can be prepared either from vindoline and catharanthine [6] [15] or from leurosine, [16] in both cases by synthesis of anhydrovinblastine. The leurosine pathway uses the Nugent–RajanBabu reagent in a highly chemoselective de-oxygenation of leurosine. [17] [16] Anhydrovinblastine is then reacted sequentially with N-bromosuccinimide and trifluoroacetic acid followed by silver tetrafluoroborate to yield vinorelbine. [15]

Vinorelbine from leurosine and from catharanthine plus vindoline.jpg

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.[ medical citation needed ] The oral form is not approved in the United States, or Australia.[ medical citation needed ]

Related Research Articles

<span class="mw-page-title-main">Alkaloid</span> Class of naturally occurring chemical compounds

Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar structure may also be termed alkaloids. In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen or sulfur. More rarely still, they may contain elements such as phosphorus, chlorine, and bromine.

<span class="mw-page-title-main">Chemotherapy</span> Treatment of cancer using drugs that inhibit cell division or kill cells

Chemotherapy is a type of cancer treatment that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent or it may aim to prolong life or to reduce symptoms. Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called medical oncology.

<i>Catharanthus</i> Genus of flowering plants

Catharanthus is a genus of flowering plants in the family Apocynaceae. Like the genus Vinca, they are known commonly as periwinkles. There are eight known species. Seven are endemic to Madagascar, though one, C. roseus, is widely naturalized around the world. The eighth species, C. pusillus, is native to India and Sri Lanka. The name Catharanthus comes from the Greek for "pure flower".

<span class="mw-page-title-main">Laboratoires Pierre Fabre</span>

Laboratoires Pierre Fabre is a French multinational pharmaceutical and cosmetics company. The company had a consolidated turnover of 1.978 billion euros in 2012. It is headquartered in the city of Castres, Midi-Pyrénées, France.

<span class="mw-page-title-main">Small-cell carcinoma</span> Type of malignant cancer

Small-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 tract. Compared to non-small cell carcinoma, small cell carcinoma has a shorter doubling time, higher growth fraction, and earlier development of metastases.

<span class="mw-page-title-main">Vincristine</span> Chemical compound; chemotherapy medication

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 disease, neuroblastoma, and small cell lung cancer among others. It is given intravenously.

<span class="mw-page-title-main">Pemetrexed</span> Chemical compound

Pemetrexed, sold under the brand name Alimta among others, is a chemotherapy medication for the treatment of pleural mesothelioma and non-small cell lung cancer (NSCLC)..

<i>Vinca</i> Genus of flowering plants

Vinca is a genus of flowering plants in the family Apocynaceae, native to Europe, northwest Africa and southwest Asia. The English name periwinkle is shared with the related genus Catharanthus.

<span class="mw-page-title-main">Gemcitabine</span> Chemical compound

Gemcitabine, with brand names including Gemzar, is a chemotherapy medication. It treats cancers including testicular cancer, breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and bladder cancer. It is administered by intravenous infusion. It acts against neoplastic growth, and it inhibits the replication of Orthohepevirus A, the causative agent of Hepatitis E, through upregulation of interferon signaling.

<span class="mw-page-title-main">Vinblastine</span> Chemical compound; chemotherapy medication

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 cancer, brain cancer, melanoma, and testicular cancer. It is given by injection into a vein.

<i>Catharanthus roseus</i> Species of flowering plant in the family Apocynaceae

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 endemic to Madagascar, but grown elsewhere as an ornamental and medicinal plant. It is a source of the drugs vincristine and vinblastine, used to treat cancer. It was formerly included in the genus Vinca as Vinca rosea.

<i>Vinca</i> alkaloid

Vinca alkaloids are a set of anti-mitotic and anti-microtubule alkaloid agents originally derived from the periwinkle plant Catharanthus roseus and other vinca plants. They block beta-tubulin polymerization in a dividing cell.

<span class="mw-page-title-main">Vindesine</span> Chemical compound

Vindesine, also termed Eldisine, is a semisynthetic vinca alkaloid derived from the flowering plant Catharanthus roseus. Like the natural and semisynthetic vinca alkaloids derived from this plant, vindesine is an inhibitor of mitosis that is used as a chemotherapy drug. By inhibiting mitosis, vinedsine blocks the proliferation of cells, particularly the rapidly proliferation cells of certain types of cancer. It is used, generally in combination with other chemotherapeutic drugs, in the treatment of various malignancies such as leukaemia, lymphoma, melanoma, breast cancer, and lung cancer.

<span class="mw-page-title-main">Mitotic inhibitor</span> Cell division inhibitor

A mitotic inhibitor is a drug that inhibits mitosis, or cell division. These drugs disrupt microtubules, which are structures that pull the chromosomes apart when a cell divides. Mitotic inhibitors are used in cancer treatment, because cancer cells are able to grow and eventually spread through the body (metastasize) through continuous mitotic division. Thus, cancer cells are more sensitive to inhibition of mitosis than normal cells. Mitotic inhibitors are also used in cytogenetics, where they stop cell division at a stage where chromosomes can be easily examined.

<span class="mw-page-title-main">Plant sources of anti-cancer agents</span>

Plant sources of anti-cancer agents are plants, the derivatives of which have been shown to be usable for the treatment or prevention of cancer in humans.

Tubulin inhibitors are chemotherapy drugs that interfere directly with the tubulin system, which is in contrast to those chemotherapy drugs acting on DNA. Microtubules play an important role in eukaryotic cells. Alpha- and beta-tubulin, the main components of microtubules, have gained considerable interest because of their function and biophysical properties and has become the subject of intense study. The addition of tubulin ligands can affect microtubule stability and function, including mitosis, cell motion and intracellular organelle transport. Tubulin binding molecules have generated significant interest after the introduction of the taxanes into clinical oncology and the general use of the vinca alkaloids. These compounds inhibit cell mitosis by binding to the protein tubulin in the mitotic spindle and preventing polymerization or depolymerization into the microtubules. This mode of action is also shared with another natural agent called colchicine.

<span class="mw-page-title-main">Pembrolizumab</span> Pharmaceutical drug used in cancer treatment

Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast cancer. It is given by slow injection into a vein.

This is a historical timeline of the development and progress of cancer treatments, which includes time of discovery, progress, and approval of the treatments.

<span class="mw-page-title-main">Bis(cyclopentadienyl)titanium(III) chloride</span> Chemical compound

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)2TiCl]2. It is an air sensitive green solid. The complex finds specialized use in synthetic organic chemistry as a single electron reductant.

Metronomic therapy is a new type of chemotherapy in which anti-cancer drugs are administered in a lower dose than the maximum tolerated dose repetitively over a long period to treat cancers with fewer side effects. Metronomic therapy is shown to affect both tumor microenvironment and tumor cells to achieve its therapeutic effects. Metronomic therapy is also cost-effective as a lower dose is used compared to conventional chemotherapy. The use of metronomic therapy has been extensively investigated and can be advantageous in selected group of patients. Yet, more clinical trials are necessary to generalize the method.

References

  1. 1 2 3 British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 594. ISBN   9780857111562.
  2. ↑ Marty M, Fumoleau P, Adenis A, Rousseau Y, Merrouche Y, Robinet G, et al. (November 2001). "Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients with solid tumors". Annals of Oncology. 12 (11): 1643–1649. doi: 10.1023/A:1013180903805 . PMID   11822766.
  3. 1 2 3 4 5 6 7 8 "Vinorelbine Tartrate". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
  4. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  5. ↑ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl: 10665/345533 . WHO/MHP/HPS/EML/2021.02.
  6. 1 2 3 4 Keglevich P, Hazai L, Kalaus G, Szántay C (May 2012). "Modifications on the basic skeletons of vinblastine and vincristine". Molecules. 17 (5): 5893–5914. doi: 10.3390/molecules17055893 . PMC   6268133 . PMID   22609781.
  7. 1 2 Faller BA, Pandit TN (2011). "Safety and efficacy of vinorelbine in the treatment of non-small cell lung cancer". Clinical Medicine Insights: Oncology. 5: 131–144. doi:10.4137/CMO.S5074. PMC   3117629 . PMID   21695100.
  8. ↑ Casanova M, Ferrari A, Spreafico F, Terenziani M, Massimino M, Luksch R, et al. (June 2002). "Vinorelbine in previously treated advanced childhood sarcomas: evidence of activity in rhabdomyosarcoma". Cancer. 94 (12): 3263–3268. doi: 10.1002/cncr.10600 . PMID   12115359. S2CID   21824468.
  9. ↑ del Pino BM (Feb 23, 2010). "Chemotherapy-induced Peripheral Neuropathy". NCI Cancer Bulletin . 7 (4): 6. Archived from the original on 2011-12-11.
  10. ↑ Jordan MA, Wilson L (April 2004). "Microtubules as a target for anticancer drugs". Nature Reviews. Cancer. 4 (4): 253–265. doi:10.1038/nrc1317. PMID   15057285. S2CID   10228718.
  11. ↑ Hirata K, Miyamoto K, Miura Y (1994). "Catharanthus roseus L. (Periwinkle): Production of Vindoline and Catharanthine in Multiple Shoot Cultures". In Bajaj YP (ed.). Biotechnology in Agriculture and Forestry 26. Medicinal and Aromatic Plants. Vol. VI. Springer-Verlag. pp.  46–55. ISBN   9783540563914.
  12. ↑ Gansäuer A, Justicia J, Fan C, Worgull D, Piestert F (2007). "Reductive C—C bond formation after epoxide opening via electron transfer". In Krische MJ (ed.). Metal Catalyzed Reductive C—C Bond Formation: A Departure from Preformed Organometallic Reagents. Topics in Current Chemistry. Vol. 279. Springer Science & Business Media. pp. 25–52. doi:10.1007/128_2007_130. ISBN   9783540728795. Archived from the original on 2017-08-01.
  13. ↑ Cooper R, John J (2016). "Africa's gift to the world". Botanical Miracles: Chemistry of Plants That Changed the World. CRC Press. pp. 46–51. ISBN   9781498704304. Archived from the original on 2017-08-01.
  14. ↑ Raviña E (2011). "Vinca alkaloids". The evolution of drug discovery: From traditional medicines to modern drugs. John Wiley & Sons. pp. 157–159. ISBN   9783527326693. Archived from the original on 2017-08-01.
  15. 1 2 Ngo QA, Roussi F, Cormier A, Thoret S, Knossow M, Guénard D, Guéritte F (January 2009). "Synthesis and biological evaluation of vinca alkaloids and phomopsin hybrids". Journal of Medicinal Chemistry. 52 (1): 134–142. doi:10.1021/jm801064y. PMID   19072542.
  16. 1 2 Hardouin C, Doris E, Rousseau B, Mioskowski C (April 2002). "Concise synthesis of anhydrovinblastine from leurosine". Organic Letters. 4 (7): 1151–1153. doi:10.1021/ol025560c. PMID   11922805.
  17. ↑ Morcillo SP, Miguel D, Campaña AG, de Cienfuegos LÁ, Justicia J, Cuerva JM (2014). "Recent applications of Cp2TiCl in natural product synthesis". Organic Chemistry Frontiers . 1 (1): 15–33. doi: 10.1039/c3qo00024a .
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.