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

Paclitaxel-loaded polymeric micelle is a novel Cremophor EL-free formulation of paclitaxel that showed antitumor activity against nonsmall-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 nonsmall-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/m² plus cisplatin 60 mg/m² or paclitaxel 175 mg/m ² 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.