Phase I pharmacokinetic study of a weekly liposomal paclitaxel formulation (Genexol®-PM) in patients with solid tumors

Background: The aim of this study was to determine the maximum tolerated dose (MTD) and the pharmacokinetic profile of Genexol-PM in Asian cancer patients. Materials and methods: Patients (N = 24) refractory to previous chemotherapy received Genexol-PM as an 1-h infusion on a weekly basis for 3 weeks followed by a resting week. The starting dose was 80 mg/m(2) and the maximum administered dose was 200 mg/m(2). Results: The majority of patients had lung, nasopharyngeal and breast cancers and in eleven patients (46%), taxane-based chemotherapy had previously failed. The MTD was defined at 180 mg/m(2). The most common grade 3 non-hematologic adverse events in cycle 1 were fatigue (4%) and neuropathy (4%) occurring mainly at 200 mg/m(2). Five (21%) patients had partial response, nine (38%) had stable disease and seven (29%) had disease progression. Five of 11 previously taxane-refractory patients showed clinical benefit to Genexol-PM. The pharmacokinetics of Genexol-PM displayed dose-proportionality, with both the maximum concentration (C-max) and the area under the concentration-time curve from zero to infinity (AUC(0-infinity)) increasing by approximately four-and threefold, respectively, as the dose of Genexol-PM was escalated from 80 to 200 mg/m(2). The median total-body clearance of Genexol-PM for all patients was 43.9 l/h. Conclusion: The weekly regimen of Genexol-PM was well tolerated and responses were observed in patients with refractory tumors, including patients who had failed taxane-based chemotherapy previously.