Phase 1-2a Multicenter Dose-Ranging Study of Canfosfamide in Combination with Carboplatin and Paclitaxel as First-Line Therapy for Patients with Advanced Non-small Cell Lung Cancer

Introduction: We aimed to evaluate the safety and efficacy of canfosfamide in combination with carboplatin and paclitaxel as first-line therapy in patients with locally advanced or metastatic non-small cell lung cancer. Methods: This was a phase 1-2a, multicenter, dose-ranging trial that enrolled patients with stage IIIB or IV non-small cell lung cancer with measurable disease. Patients received canfosfamide in doses ranging from 400 to 1000 mg/m(2) intravenously (IV) with carboplatin at area under the curve 6 IV and paclitaxel at 200 mg/m(2) IV day I every 3 weeks. The primary end point was objective response rate, and the secondary endpoints were safety and progression-free survival. Results: One hundred twenty-nine patients were treated with canfosfamide at dose levels of 400 (n = 3), 500 (n = 51), 750 (n = 54), and 1000 mg/m(2) (n = 21). Objective tumor responses by RECIST were observed in 40 patients [34% (95% confidence interval [CI], 26-44)], the median progression-free survival was 4.3 months (95% Cl, 3.7-5.2) and the median survival 9.9 months (95% Cl, 7.7-11.9). The percent of patients alive at I year was 43.1%. The overall safety profile of the combination was acceptable and consistent with the profiles of the individual agents. In an exploratory analysis, patients receiving the optional maintenance canfosfamide therapy had a prolonged median Survival of 16.8 months compared with those eligible for but not receiving maintenance therapy at 8.8 months (hazard ratio = 0.38, p < 0.001). Conclusions: The combination of canfosfamide with carboplatin and paclitaxel chemotherapy is well tolerated and active. Maintenance canfosfamide may further improve outcomes. This regimen is worthy of additional study.