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

• Published in: Journal of thoracic oncology Vol. 4; no. 11; pp. 1389 - 1396
• Main Authors: Sequist, Lecia V., Fidias, Panos M., Temel, Jennifer S., Kolevska, Tatjana, Rabin, Michael S., Boccia, Ralph V., Burris, Howard A., Belt, Robert J., Huberman, Mark S., Melnyk, Ostap, Mills, Glenn M., Englund, Craig W., Caldwell, David C., Keck, James G., Meng, Lisa, Jones, Marsha, Brown, Gail L., Edelman, Martin J., Lynch, Thomas J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2009; International Association for the Study of Lung Cancer
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - administration & dosage; Canfosfamide; Carboplatin; Carboplatin - administration & dosage; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Cytotoxins; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Glutathione - administration & dosage; Glutathione - analogs & derivatives; Humans; Injections, Intravenous; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Middle Aged; Neoplasm Staging; NSCLC; Paclitaxel; Paclitaxel - administration & dosage; Phase 2; Treatment Outcome; Carboplatin; Canfosfamide; Phase 2; NSCLC; Paclitaxel
• ISSN: 1556-0864; 1556-1380; 1556-1380
• DOI: 10.1097/JTO.0b013e3181b6b84b

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. 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/m2 intravenously (IV) with carboplatin at area under the curve 6 IV and paclitaxel at 200 mg/m2 IV day 1 every 3 weeks. The primary end point was objective response rate, and the secondary endpoints were safety and progression-free survival. 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/m2 (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% CI, 3.7–5.2) and the median survival 9.9 months (95% CI, 7.7–11.9). The percent of patients alive at 1 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). 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.