Safety and Tolerability of Weekly Genexol-PM, a Cremophor-Free Polymeric Micelle Formulation of Paclitaxel, with Carboplatin in Gynecologic Cancer: A Phase I Study

PURPOSE: This phase I study was conducted to determine the maximum tolerated dose and the recommended phase II dose of weekly administered Genexol-PM combined with carboplatin in patients with gynecologic cancer. MATERIALS AND METHODS: This open-label, phase I, dose-escalation study of weekly Genexol-PM included 18 patients with gynecologic cancer, who were equally divided into three cohorts of dose levels. Cohort 1 received 100 mg/m(2) Genexol-PM and 5 area under the curve (AUC) carboplatin, cohort 2 received 120 mg/m(2) Genexol-PM and 5 AUC carboplatin, and cohort 3 received 120 mg/m(2) Genexol-PM and 6 AUC carboplatin. The safety and efficacy of each dose were analyzed for each cohort. RESULTS: Of the 18 patients, 11 patients were newly diagnosed and seven patients were recurrent cases. No dose-limiting toxicity was observed. The maximum tolerated dose was not defined, but a dose up to 120 mg/m(2) of Genexol-PM in combination with AUC 5–6 of carboplatin could be recommended for a phase II study. In this intention-to-treat population, five patients dropped out of the study (carboplatin-related hypersensitivity, n=1; refusal of consent, n=4). Most patients (88.9%) with adverse events recovered without sequelae, and no treatment-related death occurred. The overall response rate of weekly Genexol-PM in combination with carboplatin was 72.2%. CONCLUSION: Weekly administered Genexol-PM with carboplatin demonstrated an acceptable safety profile in gynecologic cancer patients. The recommended phase II dose of weekly Genexol-PM is up to 120 mg/m(2) when combined with carboplatin.