VINORELBINE - A NOVEL VINCA ALKALOID

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adve rse effects, and dosage and administration of vinorelbine are reviewed . Vinorelbine is a semisynthetic vinca alkaloid with a broader spectru m of antitumor activity in vitro than naturally occurring vinca alkalo ids have. Vinorelbine shows selective activity against mitotic microtu bules. Higher concentrations of vinorelbine relative to vinblastine an d vincristine are required to affect axonal microtubules; presumably t his accounts for the decreased neurotoxicity of vinorelbine. Vinorelbi ne is lipophilic and is rapidly distributed into peripheral tissues. I t is highly bound to blood components. Vinorelbine is excreted slowly by the fecal route and rapidly by the urinary route. Disposition is ch aracterized by a three-compartment model, high systemic clearance, and a long terminal-phase elimination half-life. In clinical studies, vin orelbine has shown antitumor activity both as a single agent and in co mbination with cisplatin in patients with nonsmall-cell lung cancer (N SCLC). Vinorelbine plus cisplatin produces a higher response rate and longer survival than vindesine plus cisplatin, a combination previousl y found to be superior to best supportive care. Encouraging results fo r vinorelbine in the treatment of advanced breast cancer, advanced ova rian epithelial cancer, and other tumors have also been observed. The dose-limiting adverse effect of vinorelbine is myelosuppression. Vinor elbine has FDA-approved labeling for use alone or in combination with cisplatin for the first-line treatment of unresectable,advanced NSCLC. The recommended dosage is 30 mg/sq m i.v. weekly administered by eith er slow i.v. push or i.v. infusion. Vinorelbine alone or in combinatio n with other antineoplastics has shown activity against NSCLC, advance d breast cancer, and other malignancies. More study is needed to deter mine whether vinorelbine is superior to best supportive care in patien ts with NSCLC.