Paclitaxel-Loaded Polymeric Micelle (230 mg/m(2)) and Cisplatin (60 mg/m(2)) vs. Paclitaxel (175 mg/m(2)) and Cisplatin (60 mg/m(2)) in Advanced Non-Small-Cell Lung Cancer: A Multicenter Randomized Phase IIB Trial

Abstract

Paclitaxel-loaded polymeric micelle is a novel Cremophor EL-free formulation of paclitaxel that showed antitumor activity against non-small-cell lung cancer. We performed a phase IIB trial to evaluate that the response rate of paclitaxel-loaded polymeric micelle plus cisplatin is not inferior to those of a paclitaxel plus cisplatin regimen in patients with advanced non-small-cell lung cancer and who are chemonaive. The efficacy of paclitaxel-loaded polymeric micelle plus cisplatin was noninferior to that of paclitaxel plus cisplatin, and the overall incidence of adverse events was similar for both groups. Introduction: The development of paclitaxel-loaded polymeric micelle (PPM) has circumvented many of the infusion-related difficulties associated with standard solvent-based paclitaxel. PPM plus cisplatin combination chemotherapy showed significant antitumor activity in phase I and II studies. This prospective randomized controlled phase IIB study assessed the noninferiority of the efficacy and tolerability of high-dose PPM plus cisplatin to a standard dose of paclitaxel plus cisplatin. Patients and Methods: Patients with stage IIIB/IV or recurrent non-small-cell lung cancer (NSCLC) who were chemonaive were eligible for participation. The patients were randomly assigned to receive PPM 230 mg/m(2) plus cisplatin 60 mg/m(2) or paclitaxel 175 mg/m(2) plus cisplatin 60 mg/m(2) once every 3-week cycle. The primary endpoint was to compare the response rate (RR) between the groups with coprimary analyses to assess noninferiority. Secondary endpoints included progression-free survival, overall survival, and safety. Results: A total of 276 patients were randomized to PPM plus cisplatin (n = 140) or paclitaxel plus cisplatin (n = 136). RR was 43.6% in the PPM plus cisplatin group and 41.9% in the paclitaxel plus cisplatin group. Noninferiority of PPM plus cisplatin compared with paclitaxel plus cisplatin was confirmed for RR. There were no differences in progression-free survival and overall survival between the groups. Although there was a higher rate of grade 3 neutropenia in the PPM plus cisplatin group, the overall rate of adverse events was comparable between the 2 groups. Conclusion: PPM in combination with cisplatin was well tolerated, and its response rate was noninferior to that of paclitaxel plus cisplatin in patients with advanced NSCLC and who were chemonaive. Clinical Lung Cancer, Vol. 14, No. 3, 275-82 (C) 2013 Elsevier Inc. All rights reserved.