Navelbine

Vinorelbine
Systematic (IUPAC) name
	4-(acetyloxy)- 6,7-didehydro- 15-((2R,6R,8S)-4-ethyl- 1,3,6,7,8,9-hexahydro- 8-(methoxycarbonyl)- 2,6-methano- 2H-azecino(4,3-b)indol-8-yl)- 3-hydroxy- 16-methoxy- 1-methyl- methyl ester,
Clinical data
Trade names	Navelbine
AHFS/Drugs.com	monograph
MedlinePlus	a695013
Pregnancy	AU: D; US: D Evidence of risk; ;
Administration	intravenous, oral
Legal status
Legal status	UK: POM Prescription only; US: ℞-only;
Pharmacokinetic data
Bioavailability	43 ± 14% (oral)
Protein binding	79 to 91%
Metabolism	Hepatic (CYP3A4-mediated)
Biological half-life	27.7 to 43.6 hours
Excretion	Fecal (46%) and renal (18%)
Identifiers
CASRN	71486-22-1
ATC code	L01CA04 (WHO)
PubChem	CID 5311497
DrugBank	DB00361
ChemSpider	4470974
UNII	Q6C979R91Y
KEGG	D08680
ChEMBL	CHEMBL607994
Chemical data
Formula	C45H54N4O8
Molar mass	778.932 g/mol
	SMILES O=C(OC)[C@]4(c2nc1ccccc1c2CN3CC(=C/[C@H](C3)C4)\CC)c5c(OC)cc6c(c5)[C@@]89[C@@H](N6C)[C@@](O)(C(=O)OC)[C@H](OC(=O)C)[C@@]7(/C=C\CN([C@@H]78)CC9)CC ;
	InChI 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 ; Key:GBABOYUKABKIAF-IELIFDKJSA-N ;
(what is this?) (verify)

ビノレルビン。ナベルビン

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/05/24 22:33:22」(JST)

wiki en

[Wiki en表示]

Vinorelbine (NVB), sold under the trade name Navelbine, is a chemotherapy medication that is used to treat a number of types of cancer, including breast cancer and non-small cell lung cancer.^[2]

It is on the World Health Organization's List of Essential Medicines, the most important medication needed in a basic health system.^[3] The wholesale price as of 2014 is between 8.60 and 42.80 USD a vial.^[4]^[5]

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. It is also active in rhabdomyosarcoma.^[6]

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^[7]), lowered resistance to infection, bruising or bleeding, anaemia, constipation, 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.^[8] Vinorelbine is the first 5´NOR semi-synthetic vinca alkaloid. It is obtained by semi-synthesis from alkaloids extracted from the rosy periwinkle, Catharanthus roseus. It is marketed in India by Abbott Healthcare under the brand name Navelbine.

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. It is a semi-synthetic vinca alkaloid. 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.

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]}

References

^ Marty M, Fumoleau P, Adenis A, Rousseau Y, Merrouche Y, Robinet G, Senac I, Puozzo C (2001). "Oral vinorelbine pharmacokinetics and absolute bioavailability study in patients with solid tumors". Ann Oncol 12 (11): 1643–9. doi:10.1023/A:1013180903805. PMID 11822766.
^ "Navelbine". The American Society of Health-System Pharmacists. Retrieved Nov 28, 2015.
^ "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Retrieved May 10, 2015.
^ "Vinorelbine". International Drug Price Indicator Guide. Retrieved 28 November 2015.
^ "Vinorelbine". International Drug Price Indicator Guide. Retrieved 28 November 2015.
^ Casanova, M; Ferrari, A; Spreafico, F; Terenziani, M; Massimino, M; Luksch, R; Cefalo, G; Polastri, D; et al. (2002). "Vinorelbine in previously treated advanced childhood sarcomas: Evidence of activity in rhabdomyosarcoma". Cancer 94 (12): 3263–8. doi:10.1002/cncr.10600. PMID 12115359.
^ del Pino BM. Chemotherapy-induced Peripheral Neuropathy. NCI Cancer Bulletin. Feb 23, 2010;7(4):6.
^ Jordan, M.A.; Wilson, L. (2004). "Microtubules as a target for anticancer drugs.". Nature Reviews. Cancer 4 (4): 253–65. doi:10.1038/nrc1317. PMID 15057285.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 高齢患者およびperformance statusのスコアが低い患者における進行非小細胞肺癌に対する全身療法 systemic therapy for advanced non small cell lung cancer in elderly patients and patients with a poor performance status
2. 女性の転移性乳癌に対する全身療法：化学療法 systemic treatment of metastatic breast cancer in women chemotherapy
3. ドライバー変異が認められない進行非小細胞肺癌の初期マネージメントのための全身療法 systemic therapy for the initial management of advanced non small cell lung cancer without a driver mutation
4. 非小細胞肺癌の治療プロトコル treatment protocols for non small cell lung cancer
5. 高齢女性における転移性乳癌の治療 treatment of metastatic breast cancer in older women

English Journal

Safety and tolerability of eribulin mesylate in patients with pretreated metastatic breast cancer.

Goodin S1, Barbour S2, Song J2, Berrak E2, Cox D2.
American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.Am J Health Syst Pharm.2015 Dec 15;72(24):2150-6. doi: 10.2146/ajhp140773.
PURPOSE: The safety and tolerability of eribulin mesylate for the treatment of metastatic breast cancer (MBC) are examined.METHODS: This retrospective analysis used pooled safety and tolerability data from three Phase II trials and one Phase III trial of eribulin in patients with MBC. In these studi
PMID 26637514

Sequential use of vinorelbine followed by gefitinib enhances the antitumor effect in NSCLC cell lines poorly responsive to reversible EGFR tyrosine kinase inhibitors.

Dal Bello MG1, Alama A1, Barletta G1, Coco S1, Truini A1,2, Vanni I1, Boccardo S3, Genova C1, Rijavec E1, Biello F1, Bottoni G4, Sambuceti G4, Grossi F1.
International journal of cancer. Journal international du cancer.Int J Cancer.2015 Dec 15;137(12):2947-58. doi: 10.1002/ijc.29647. Epub 2015 Jul 15.
Preclinical studies have suggested that combining cytotoxic agents with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) to treat EGFR-mutated tumors may increase their inhibitory effect depending on the order of drug administration. The antitumor efficacy of different treatme
PMID 26089022

Phase III Study of Surgery Versus Definitive Concurrent Chemoradiotherapy Boost in Patients With Resectable Stage IIIA(N2) and Selected IIIB Non-Small-Cell Lung Cancer After Induction Chemotherapy and Concurrent Chemoradiotherapy (ESPATUE).

Eberhardt WE1, Pöttgen C2, Gauler TC2, Friedel G2, Veit S2, Heinrich V2, Welter S2, Budach W2, Spengler W2, Kimmich M2, Fischer B2, Schmidberger H2, De Ruysscher D2, Belka C2, Cordes S2, Hepp R2, Lütke-Brintrup D2, Lehmann N2, Schuler M2, Jöckel KH2, Stamatis G2, Stuschke M2.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology.J Clin Oncol.2015 Dec 10;33(35):4194-201. doi: 10.1200/JCO.2015.62.6812. Epub 2015 Nov 2.
PURPOSE: Concurrent chemoradiotherapy with or without surgery are options for stage IIIA(N2) non-small-cell lung cancer. Our previous phase II study had shown the efficacy of induction chemotherapy followed by chemoradiotherapy and surgery in patients with IIIA(N2) disease and with selected IIIB dis
PMID 26527789

Japanese Journal

Adjuvant chemotherapy for completely resected non-small-cell lung cancer

Acta Medica Okayama 63(5), 223-230, 2009-10
NAID 120002312601

What's going on 肺癌 Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage 1 B-3 A non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association <ANITA>): a randomised controlled trial. Douillard JY, et al. Lancet Oncol. 2006; 7: 719-27. PMID: 16945766

Mebio oncology 4(1), 82-85, 2007
NAID 40015444795

Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]) : a randomised controlled trial

Lancet Oncol 7, 719-727, 2006
NAID 30010003406

Related Pictures

Навельбин (Navelbine, Vinorelbine) NAVELBINE 20 MG 1 CAP price from seif in Egypt - Yaoota! Products - Navelbine Manufacturer in Turkey by Pharma Mango | ID - 541960 Navelbine - patient information, description, dosage and directions. navelbine iv/oral softgel 20 mg, 20 mg, Capsule, MIMS.com Navelbine Intravenous : Uses, Side Effects, Interactions, Pictures, Warnings & Dosing