Phase I/II trial of weekly intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with stage IV non-small-cell lung cancer

Purpose Nanoparticle albumin-bound paclitaxel ( NAB-paclitaxel) is an albumin-bound formulation of paclitaxel that has demonstrated improved efficacy compared with paclitaxel in the treatment of metastatic breast cancer. We undertook this trial to determine the maximum-tolerated dose ( MTD) and single-agent activity of NAB-paclitaxel administered on a weekly basis to patients with stage IV non-small-cell lung cancer ( NSCLC). Patients and Methods This was an open-label, single-arm, phase I/II study. Patients were treated with NAB-paclitaxel intravenously during 30 minutes without corticosteroid or antihistamine premedications on days 1, 8, and 15 of a 28-day cycle. Radiologic tumor assessment was performed every 8 weeks. Results Dose levels of 100 and 125 mg/m(2) were tolerated without dose-limiting toxicities ( DLTs). At 150 mg/m(2) the MTD was exceeded; two of three patients experienced a DLT ( grade 3 sensory neuropathy and febrile neutropenia). The 125 mg/m(2) dose level was expanded and determined to be the MTD. A total of 40 patients were treated at 125 mg/m(2). The objective response rate was 30% ( 12 of 40 patients; 95% CI, 16% to 44%), median time to progression was 5 months ( 95% CI, 3 to 8 months), and median overall survival was 11 months ( 95% CI, 7 months to not reached). The 1-year survival was 41%. Conclusion NAB-paclitaxel 125 mg/m(2) administered on days 1, 8, and 15 of a 28-day cycle was well tolerated and demonstrated encouraging single-agent activity. No corticosteroid premedication was administered and no hypersensitivity reactions were seen. Additional studies of single-agent NAB-paclitaxel as well as platinum-based combinations are warranted.