An Open-Label, Multicenter, Phase I Trial Of A Cremophor-Free, Polymeric Micelle Formulation Of Paclitaxel Combined With Carboplatin As A First-Line Treatment For Advanced Ovarian Cancer: A Korean Gynecologic Oncology Group Study (Kgog-3016)

Objective: This phase I study aimed to determine the maximum tolerated dose (MTD) of Genexol-PM, when combined with carboplatin, as a first-line treatment in patients with advanced ovarian cancer.Methods: This open-label, multicenter, phase I, dose-escalation study included 18 patients (median age: 59.0 years, range: 40-75 years) diagnosed with advanced epithelial ovarian cancer. All patients had measurable residual disease after debulking surgery. Patients were assigned to groups (n=6 each group) that received different doses of Genexol-PM (220, 260, and 300 mg/m(2), once every 3 weeks) and 5 area under the curve (AUC) carboplatin. Safety and efficacy were analyzed for each dose group.Results: In this intention-to-treat population, 3 out of 18 patients dropped out of the study: 1 due to dose-limiting toxicity (DLT), 1 due to hypersensitivity, and 1 was lost during follow-up. DLTs were not reported at 220 mg/m(2) or 260 mg/m(2), but at 300 mg/m(2), 1 patient experienced DLT (grade 3 general pain). The MTD of Genexol-PM was not determined, but a dose of 300 mg/m(2) or less could be recommended for the phase II study. Most patients (73.9%) with adverse events recovered without sequelae, and no death occurred that was related to the disease or treatment. The best overall response rate was 94.1%.Conclusion: Genexol-PM combined with carboplatin was well tolerated as a first-line treatment, and good responses were observed in patients with advanced ovarian cancer. Based on these results, we recommended a dose of 300 mg/m(2) or less for a phase II study.