A phase I pharmacokinetic study of a liposomal formulation of paclitaxel administered weekly to Asian patients with solid malignancies
2581 Background: Genexol-PM is a sterile, lyophilized polymeric micellar formulation of paclitaxel which is devoid of Cremophor EL and hence is more tolerable and less toxic. This phase 1 study sought to determine the maximum tolerated dose and the pharmacokinetic profile of Genexol-PM in Asian cancer patients with solid malignancies. Methods: Patients (N=35) refractory to previous chemotherapy were enrolled in a phase 1, open-label, dose-escalating study to assess safety, tolerability ad pharmacokinetics of Genexol-PM administered as a 1h infusion on a weekly basis for 3 weeks followed by a resting week. The starting dose was 80mg/m2. Cohorts of 1–6 patients were treated at 100, 120, 140, 160, 180 and the maximum administered dose was 200 mg/m2. Results: The median age was 56 years (range: 39 - 67 years) and two thirds of the enrolled patients were male (67%). Twenty-three patients (96%) had received prior chemotherapy, including eleven patients (46%) who had previously received taxane-based chemotherapy. The majority of patients had lung, nasopharyngeal and breast cancers. DLT was reached at 200 mg/m2. The MTD was 180 mg/m2. Grade 3 granulocytopenia was common in patients receiving Genexol-PM at doses of 120 mg/m2 or higher in the first cycle. The most common grade 3 non-haematologic adverse events in cycle 1 were fatigue, myalgia and neuropathy and occurred mainly at dose level 7 (200 mg/m2) in 4%, 4% and 8% of the patients. Five (21%) patients had partial response, 9 (38%) had stable disease and seven (29%) patients had disease progression. The pharmacokinetics of Genexol-PM displayed dose-proportionality, with both Cmax and AUC0-∞ values increasing by approximately 4- and 3-fold as the dose of Genexol-PM was increased from 80mg/m2 to 200mg/m2 with no significant change in clearance. The median total-body clearance of Genexol-PM for all patients was 43.9 L/hr. Conclusions: The weekly regimen of Genexol-PM was found to be well-tolerated and responses were observed in patients with refractory tumours, including patients who had failed taxane-based chemotherapy previously. No significant financial relationships to disclose.