Vinorelbine

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
  • AU: D
  • US: D (Evidence of risk)
intravenous, oral
Pharmacokinetic data
Bioavailability 43 ± 14% (oral)[1]
Protein binding 79 to 91%
Metabolism Hepatic (CYP3A4-mediated)
Half-life 27.7 to 43.6 hours
Excretion Fecal (46%) and renal (18%)
Identifiers
71486-22-1 Yes
L01CA04
PubChem CID 5311497
DrugBank DB00361 Yes
ChemSpider 4470974 Yes
UNII Q6C979R91Y Yes
KEGG D08680 Yes
ChEMBL CHEMBL607994 
Chemical data
Formula C45H54N4O8
778.932 g/mol
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Vinorelbine (trade name Navelbine) is an anti-mitotic chemotherapy drug that is given as a treatment for some types of cancer, including breast cancer and non-small cell lung cancer.

Clinicians sometimes use the abbreviation "NVB" for vinorelbine, although (like many medical abbreviations) it is not a unique identifier.

Pharmacology

The antitumor activity is due to inhibition of mitosis through interaction with tubulin.[2] 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.

Uses

Vinorelbine is approved for the treatment of non-small-cell lung cancer and metastatic breast cancer. It is also active in rhabdomyosarcoma.[3]

Oral formulation

An oral formulation has been marketed and registered in most European countries for the same settings. It has similar efficacy as the intravenous formulation, avoids venous toxicities of an infusion and is easier to take. Oral form is not apprived in the US or Australia.

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[4]), 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.

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ del Pino BM. Chemotherapy-induced Peripheral Neuropathy. NCI Cancer Bulletin. Feb 23, 2010;7(4):6.