Paclitaxel-Loaded Polymeric Micelle (230 mg/m2) and Cisplatin (60 mg/m2) vs. Paclitaxel (175 mg/m2) and Cisplatin (60 mg/m2) 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.PPMplus 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/m2 plus cisplatin 60 mg/m2 or paclitaxel 175 mg/m2 plus cisplatin 60 mg/m2 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.