Vinorelbine

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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) [3]
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. [4] This includes breast cancer and non-small cell lung cancer. [4] It is given by injection into a vein or by mouth. [4] [1]

Contents

Common side effects include bone marrow suppression, pain at the site of injection, vomiting, feeling tired, numbness, and diarrhea. [4] Other serious side effects include shortness of breath. [4] Use during pregnancy may harm the baby. [4] 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. [4]

Vinorelbine was approved for medical use in the United States in 1994. [4] It is on the World Health Organization's List of Essential Medicines. [5] [6]

Medical uses

Vinorelbine is approved for the treatment of non-small-cell lung cancer. [7] [8] It is used off-label for other cancers such as metastatic breast cancer and for aggressive fibromatosis (desmoid tumor). [9] [10] It is also active in rhabdomyosarcoma. [11]

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 [12] ), 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. [13]

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 [14] 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. [15] [16] [7] [17] The newer semi-synthetic chemotherapeutic agent vinorelbine, which is used in the treatment of non-small-cell lung cancer [7] [8] and is not known to occur naturally. However, it can be prepared either from vindoline and catharanthine [7] [18] or from leurosine, [19] in both cases by synthesis of anhydrovinblastine. The leurosine pathway uses the Nugent–RajanBabu reagent in a highly chemoselective de-oxygenation of leurosine. [20] [19] Anhydrovinblastine is then reacted sequentially with N-bromosuccinimide and trifluoroacetic acid followed by silver tetrafluoroborate to yield vinorelbine. [18]

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">Chemotherapy</span> Treatment of cancer using drugs that inhibit cell division or kill cells

Chemotherapy is the type of cancer treatment that uses one or more anti-cancer drugs in a standard regimen. Chemotherapy may be given with a curative intent, or it may aim only 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.

<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 is more aggressive, with 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.

Bevacizumab, sold under the brand name Avastin among others, is a monoclonal antibody medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (intravenous) and used for colon cancer, lung cancer, ovarian cancer, glioblastoma, hepatocellular carcinoma, and renal-cell carcinoma. In many of these diseases it is used as a first-line therapy. For age-related macular degeneration it is given by injection into the eye (intravitreal).

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

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<span class="mw-page-title-main">Vinblastine</span> 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 is grown elsewhere as an ornamental and medicinal plant, and now has a pantropical distribution. 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.

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

Thiotepa (INN), sold under the brand name Tepadina, is a medication used to treat cancer.

<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, microtubule inhibitor, or tubulin inhibitor, is a drug that inhibits mitosis, or cell division, and is used in treating cancer, gout, and nail fungus. 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 through continuous division that eventually spread through the body (metastasize). 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.

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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.

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Lurbinectedin, sold under the brand name Zepzelca, is a medication used for the treatment of small cell lung cancer.

<span class="mw-page-title-main">Dimerization of catharanthine and vindoline</span>

Catharanthine and vindoline are terpenoid indole alkaloids naturally produced within the Madagascar periwinkle plant whose dimerization produces the anti-cancer drugs vinblastine and vincristine. The precursor of catharanthine and vindoline is strictosidine, the common precursor of all indole alkaloids. The localization of catharanthine and vindoline within the plant tissue has been heavily studied in recent years with conflicting results. The dimerization of catharanthine and vindoline to form vinblastine and vincristine is catalyzed by a peroxidase and a reductase, and includes several intermediate compounds.

References

  1. 1 2 3 British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 594. ISBN   9780857111562.
  2. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 Oct 2023.
  3. ↑ 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.
  4. 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.
  5. ↑ 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.
  6. ↑ 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.
  7. 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.
  8. 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.
  9. ↑ Saiyed MM, Ong PS, Chew L (June 2017). "Off-label drug use in oncology: a systematic review of literature". Journal of Clinical Pharmacy and Therapeutics. 42 (3): 251–258. doi:10.1111/jcpt.12507. PMID   28164359.
  10. ↑ "The management of desmoid tumours: A joint global consensus-based guideline approach for adult and paediatric patients". European Journal of Cancer. 127: 96–107. March 2020. doi:10.1016/j.ejca.2019.11.013. PMID   32004793.
  11. ↑ 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.
  12. ↑ del Pino BM (Feb 23, 2010). "Chemotherapy-induced Peripheral Neuropathy". NCI Cancer Bulletin . 7 (4): 6. Archived from the original on 2011-12-11.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ 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.
  18. 1 2 Ngo QA, Roussi F, Cormier A, Thoret S, Knossow M, Guénard D, et al. (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.
  19. 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.
  20. ↑ 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 . hdl: 10481/47295 .
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