VINORELBINE

Vinorelbine is a cytostatic antineoplastic drug. It is a semi-synthetic member of the vinca alkaloid family that interferes with microtubule assembly. The vinca alkaloids are structurally similar compounds comprised of two multiringed units, vindoline and catharanthine. Unlike other vinca alkaloids, the catharanthine unit is the site of structural modification for vinorelbine. The antitumor activity of vinorelbine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. In intact tectal platesw from mouse embryos, vinorelbine, vincristine, and vinblastine inhibited mitotic microtubule formation at the same concentration (2micoM), including a blockade of cells at metaphase. Vincristine produced depolymerisation of axonal tubules at 5 microM, but vinblastine and vinorelbine dis not have this effect until concentrations of 30microM and 40microM respectively. These date suggest relative selectivity of vinorelbine for mitotic microtubules. Vinorelbine has an active metabolite, 17 deacetylvinorelbine, low levels of which are recovered in human: its toxicity and activity are slightly higher than those of vinorelbine.

Indications

The tdreatment of non small cell lung cancer (NSCLS), and the second line treatment of advanced breast cancer.

Dosage

Single agent tratment in usually given at 25-30mg/m2 weekly. In combination chemotherapy the dose may be the same and frequency of administration reduced, ie: day 1 and 8 or day 1 and 5 every 3 weeks. Clinical experience has not identified differences in response between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Contra-Indications

Hypersensitivity to vinorelbhine, Neutrophil counts ncy, Lactation.

Special Precautions

Injection must only be administered by the intravenous route. Intrathecal administration of other vinca alkaloids has resulted in death. Improper administration of Temozolomide may result in extravasation causing local tissue necrosis and/or thrombophlebitis. Should be frequently monitored for myelosupporession both during and after therapy. Neutropenia is dose-limiting.