Phase I Study of Liposomal Vincristine

PURPOSE: A phase I study of vincristine encapsulated inside 120-nm-diameter distearoylphosphatidylcholine-cholesterol liposomes was performed. The primary objectives were to determine the maximum-tolerated dose (MTD), recommended phase II dose, toxicity, and pharmacokinetics of liposomal vincristine (ONCO-TCS). PATIENTS AND METHODS: Twenty-five patients with histologically confirmed malignancies were enrolled and assessable. Vincristine doses were increased from 0.5 mg/m2 to 1.0, 1.5, 2.0, 2.4, and 2.8 mg/m2 with cohorts of three or more patients per dose level. A total of 64 courses of ONCO-TCS were administered intravenously once every 3 weeks. The pharmacokinetics of total vincristine content in plasma were determined using a high-performance liquid chromatography method. RESULTS: Patients were treated with vincristine doses up to 2.8 mg/m2; however, 2.4 mg/m2 was defined as the MTD and 2.0 mg/m2 as the phase II recommended dose. Pain and obstipation were the dose-limiting toxicites. Other toxicities w...