Phase II Study of Nedaplatin / Irinotecan for Advanced Squamous Cell Carcinoma of the Lung(Torg0910)

Background: A synergistic interaction between nedaplatin (NP) and irinotecan (CPT) has been demonstrated in three-dimensional analytical models (Clin Cancer Res 2001). Phase I/II studies for lung cancer showed high efficacy of the combination of NP and CPT (Cancer Chemother Pharmacol 2003). In addition, a meta-analysis suggested that the combination of NP and CPT was more feasible in squamous cell carcinoma (SCC) than non-squamous cell carcinoma (J Thorac Oncol. 2011). This study explored the efficacy and safety of an NP and CPT regimen in SCC of the lung. Methods: We conducted a multicenter phase II study of NP and CPT for stage III and IV SCC of the lung. Treatment consisted of 4 to 6 cycles of NP at 100mg/m2 (day 1) and CPT at 60mg/m2 (days 1 and 8) every 4 to 5 weeks. The primary endpoint was the response rate and secondary endpoints were overall and progression-free survival rates, and safety. Results: Fifty patients were registered and evaluated. Twenty-seven patients received 4 to 6 cycles of chemotherapy. A median of 4 cycles were given. One patient achieved a complete response and sixteen showed partial responses, with an overall response rate of 34.0% (95% confidence interval 21.2% to 48.8%). The disease control rate was 74.0%. The median progression free survival time was 4.3 months. The major toxicities included grade 4 anemia (10.0%), neutropenia (46.0%) and thrombocytopenia (10.0%), and grade 3 or 4 anorexia, diarrhea, hyponatremia, febrile neutropenia and infection occurred in 22.0%, 12.0%, 12.0%, 16.0% and 10.0% of patients, respectively. All of the toxicities were manageable and no treatment-related deaths were observed. Conclusions: The NP and CPT combination therapy is feasible for patients with advanced SCC of the lung.