Vinorelbine (Navelbine). A new semisynthetic vinca alkaloid.

Vinorelbine (Navelbine) is a new, semisynthetic 5'Nor-vinca-alkaloid, modified on the catharantine ring, developed by Pierre Fabre Médicament. Vinorelbine is a potent as the other vinca alkaloids to inhibit mitotic microtubule polymerization. On the other hand, its activity is lower on axonal microtubule. Preclinical studies have shown its broad spectrum of activity in vitro and its antitumoral efficacy comparable or higher to that of other vinca alkaloids against murine tumors and in xenograft models. The main experimental toxicity of vinorelbine is a reversible leucopenia. No neurotoxicity was evidenced in rats, dogs and monkeys. After i.v. injection in patients, the plasma kinetic is described by a tricompartimental model with a high clearance, a very large volume of distribution and a long terminal half life, intermediate between vincristine and vinblastine. Tissue uptake of vinorelbine is very intense, probably related to its high liposolubility, leading to high tissue concentration compared to plasma. Phase I trial using weekly i.v. administration demonstrated a maximal tolerated dose (MTD) of 27.5 to 35.4 mg/m2 and the recommended dose was established at 30 mg/m2 weekly. In Phase II studies, Vinorelbine was shown to be effective in at least 4 types of cancer: Non-small cell lung cancer (remission rate: 33%), breast cancer (45%), advanced ovarian cancer (15% in heavily pretreated patients), Hodgkin's disease (90%). In all the trials, side effects are generally limited to a reversible and non-cumulative leucopenia. Neurotoxicity appears to be mild, similar to that observed with vinblastine and much less severe than with vincristine. No evidence of cardiac, pulmonary, renal, hepatic or other organ system toxicity has emerged.(ABSTRACT TRUNCATED AT 250 WORDS)