Vinorelbine
{{short description|Pharmaceutical drug}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 470630496
| IUPAC_name = 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
| image = Vinorelbine.svg
| image_class = skin-invert-image
| image2 = Vinorelbine ball-and-stick.png
| image_class2 = bg-transparent
| tradename = Navelbine
| Drugs.com = {{drugs.com|monograph|vinorelbine-tartrate}}
| MedlinePlus = a695013
| pregnancy_AU = D
| pregnancy_US = D
| legal_UK = POM
| legal_US = Rx-only
| routes_of_administration = intravenous, by mouth
| protein_bound = 79 to 91%
| metabolism = liver (CYP3A4-mediated)
| elimination_half-life = 27.7 to 43.6 hours
| excretion = Fecal (46%) and kidney (18%)
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 71486-22-1
| ATC_prefix = L01
| ATC_suffix = CA04
| PubChem = 5311497
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00361
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4470974
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = Q6C979R91Y
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08680
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 607994
| C=45 | H=54 | N=4 | O=8
| smiles = [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
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = GBABOYUKABKIAF-IELIFDKJSA-N
|drug_name=|alt=|caption=|type=|legal_status=|licence_EU=|pregnancy_category=|licence_US=|legal_CA=Rx-only|legal_AU=S4}}
Vinorelbine, 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 mouth.{{cite web|title=Vinorelbine Tartrate|url=https://www.drugs.com/monograph/vinorelbine-tartrate.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161221162800/https://www.drugs.com/monograph/vinorelbine-tartrate.html|archive-date=21 December 2016}}
Common side effects include bone marrow suppression, pain at the site of injection, vomiting, feeling tired, numbness, and diarrhea. Other serious side effects include shortness of breath. Use during pregnancy may harm the baby. Vinorelbine is in the vinca alkaloid family of medications.{{cite book|title=British national formulary : BNF 69|date=2015|publisher=British Medical Association|isbn=9780857111562|page=594|edition=69}} It is believed to work by disrupting the normal function of microtubules and thereby stopping cell division.
Vinorelbine was approved for medical use in the United States in 1994. It is on the World Health Organization's List of Essential Medicines.{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}
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 and for aggressive fibromatosis (desmoid tumor).{{cite journal | vauthors = Saiyed MM, Ong PS, Chew L | title = Off-label drug use in oncology: a systematic review of literature | journal = Journal of Clinical Pharmacy and Therapeutics | volume = 42 | issue = 3 | pages = 251–258 | date = June 2017 | pmid = 28164359 | doi = 10.1111/jcpt.12507 | doi-access = free }}{{cite journal | title = The management of desmoid tumours: A joint global consensus-based guideline approach for adult and paediatric patients | journal = European Journal of Cancer | volume = 127 | pages = 96–107 | date = March 2020 | pmid = 32004793 | doi = 10.1016/j.ejca.2019.11.013 | hdl = 2434/809127 | hdl-access = free | display-authors = 1 | vauthors = Alman B, Attia S, Baumgarten C, Benson C, Blay J, Bonvalot S, Breuing J, Cardona K, Casali PG, Van Coevorden F, Colombo C, Dei Tos AP, Dileo P, Ferrari A, Fiore M, Frezza AM, Garcia J, Gladdy R, Gounder M, Gronchi A, Haas R, Hackett S, Haller F, Hohenberger P, Husson O, Jones RL, Judson I, Kasper B, Kawai A, Kogosov V }} It is also active in rhabdomyosarcoma.{{cite journal | vauthors = Casanova M, Ferrari A, Spreafico F, Terenziani M, Massimino M, Luksch R, Cefalo G, Polastri D, Marcon I, Bellani FF | title = Vinorelbine in previously treated advanced childhood sarcomas: evidence of activity in rhabdomyosarcoma | journal = Cancer | volume = 94 | issue = 12 | pages = 3263–3268 | date = June 2002 | pmid = 12115359 | doi = 10.1002/cncr.10600 | s2cid = 21824468 | doi-access = free }}
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{{cite journal | vauthors = del Pino BM | date = Feb 23, 2010 | journal = NCI Cancer Bulletin | volume = 7 | issue = 4 | page = 6 | title = Chemotherapy-induced Peripheral Neuropathy | url = http://www.cancer.gov/aboutnci/ncicancerbulletin/archive/2010/022310/page6 | archive-url = https://web.archive.org/web/20111211105234/http://www.cancer.gov/aboutnci/ncicancerbulletin/archive/2010/022310/page6 | url-status = dead | archive-date = 2011-12-11 }}), 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.{{cite journal | vauthors = Jordan MA, Wilson L | title = Microtubules as a target for anticancer drugs | journal = Nature Reviews. Cancer | volume = 4 | issue = 4 | pages = 253–265 | date = April 2004 | pmid = 15057285 | doi = 10.1038/nrc1317 | s2cid = 10228718 }}
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{{cite book|chapter = Catharanthus roseus L. (Periwinkle): Production of Vindoline and Catharanthine in Multiple Shoot Cultures| vauthors = Hirata K, Miyamoto K, Miura Y |title = Biotechnology in Agriculture and Forestry 26|series = Medicinal and Aromatic Plants|volume = VI| veditors = Bajaj YP |publisher = Springer-Verlag|year = 1994|pages = [https://archive.org/details/medicinalaromati0006unse/page/46 46–55]|chapter-url = https://books.google.com/books?id=e64hCDBddowC&pg=PA47|isbn = 9783540563914|url = https://archive.org/details/medicinalaromati0006unse/page/46}} 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.{{cite book|title = Metal Catalyzed Reductive C—C Bond Formation: A Departure from Preformed Organometallic Reagents|volume = 279|series = Topics in Current Chemistry|pages = 25–52|year = 2007|chapter = Reductive C—C bond formation after epoxide opening via electron transfer | vauthors = Gansäuer A, Justicia J, Fan C, Worgull D, Piestert F |doi = 10.1007/128_2007_130|chapter-url = https://books.google.com/books?id=A5xcVmT9iIQC&pg=PA25| veditors = Krische MJ |editor-link1=Michael J. Krische |publisher = Springer Science & Business Media|isbn = 9783540728795|url-status = live|archive-url = https://web.archive.org/web/20170801195208/https://books.google.com.au/books?id=A5xcVmT9iIQC&pg=PA25|archive-date = 2017-08-01}}{{cite book|chapter = Africa's gift to the world|pages = 46–51|chapter-url = https://books.google.com/books?id=aXGmCwAAQBAJ&pg=PA46|title = Botanical Miracles: Chemistry of Plants That Changed the World| vauthors = Cooper R, John J |publisher = CRC Press|year = 2016|isbn = 9781498704304|url-status = live|archive-url = https://web.archive.org/web/20170801195333/https://books.google.com.au/books?id=aXGmCwAAQBAJ&pg=PA46|archive-date = 2017-08-01}}{{cite journal | vauthors = Keglevich P, Hazai L, Kalaus G, Szántay C | title = Modifications on the basic skeletons of vinblastine and vincristine | journal = Molecules | volume = 17 | issue = 5 | pages = 5893–5914 | date = May 2012 | pmid = 22609781 | pmc = 6268133 | doi = 10.3390/molecules17055893 | doi-access = free }}{{cite book| vauthors = Raviña E |title = The evolution of drug discovery: From traditional medicines to modern drugs|year = 2011|publisher = John Wiley & Sons|isbn = 9783527326693|pages = 157–159|chapter = Vinca alkaloids|chapter-url = https://books.google.com/books?id=iDNy0XxGqT8C&pg=PA157|url-status = live|archive-url = https://web.archive.org/web/20170801200844/https://books.google.ca/books?id=iDNy0XxGqT8C&pg=PA157|archive-date = 2017-08-01}} The newer semi-synthetic chemotherapeutic agent vinorelbine, which is used in the treatment of non-small-cell lung cancer{{cite journal | vauthors = Faller BA, Pandit TN | title = Safety and efficacy of vinorelbine in the treatment of non-small cell lung cancer | journal = Clinical Medicine Insights: Oncology | volume = 5 | pages = 131–144 | year = 2011 | pmid = 21695100 | pmc = 3117629 | doi = 10.4137/CMO.S5074 }} and is not known to occur naturally. However, it can be prepared either from vindoline and catharanthine{{cite journal | vauthors = Ngo QA, Roussi F, Cormier A, Thoret S, Knossow M, Guénard D, Guéritte F | title = Synthesis and biological evaluation of vinca alkaloids and phomopsin hybrids | journal = Journal of Medicinal Chemistry | volume = 52 | issue = 1 | pages = 134–142 | date = January 2009 | pmid = 19072542 | doi = 10.1021/jm801064y }} or from leurosine, in both cases by synthesis of anhydrovinblastine. The leurosine pathway uses the Nugent–RajanBabu reagent in a highly chemoselective de-oxygenation of leurosine.{{cite journal| vauthors = Morcillo SP, Miguel D, Campaña AG, de Cienfuegos LÁ, Justicia J, Cuerva JM |year = 2014|title = Recent applications of Cp2TiCl in natural product synthesis|journal = Organic Chemistry Frontiers|volume = 1|issue = 1|pages = 15–33|doi = 10.1039/c3qo00024a|doi-access = free|hdl = 10481/47295|hdl-access = free}}{{cite journal | vauthors = Hardouin C, Doris E, Rousseau B, Mioskowski C | title = Concise synthesis of anhydrovinblastine from leurosine | journal = Organic Letters | volume = 4 | issue = 7 | pages = 1151–1153 | date = April 2002 | pmid = 11922805 | doi = 10.1021/ol025560c }} Anhydrovinblastine is then reacted sequentially with N-bromosuccinimide and trifluoroacetic acid followed by silver tetrafluoroborate to yield vinorelbine.
File: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.{{medcn|date=May 2015}} The oral form is not approved in the United States, or Australia.{{medcn|date=May 2015}}
References
{{reflist}}
External links
- {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/vinorelbine | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Vinorelbine }}
{{Chemotherapeutic agents}}
{{portal bar|Medicine}}