Phase I Trial of Radiation With Concurrent and Consolidation Pemetrexed and Cisplatin in Patients With Unresectable Stage IIIA/B Non–Small-Cell Lung Cancer

Purpose To evaluate the feasibility and safety of concurrent pemetrexed/cisplatin/thoracic radiotherapy followed by consolidation pemetrexed/cisplatin for unresectable Stage IIIA/B non–small-cell lung cancer (NSCLC). Methods and Materials Eligible patients with 2 on Days 1 and 22 for Dose Levels 1, 2, and 3/4, respectively) and cisplatin (25 mg/m 2 Days 1–3 for Dose Levels 1–3; 20 mg/m 2 Days 1–5 for Dose Level 4) concurrent with thoracic radiation (61–66 Gy in 31–35 fractions). Consolidation consisted of two cycles of pemetrexed/cisplatin (500 mg/m 2 , 75 mg/m 2 ) 21 days apart, after concurrent therapy. Results Between January 2006 and October 2007, 16 patients entered the study. Median follow-up was 17.2 months. No dose-limiting toxicities were observed. Median radiation dose was 64 Gy (range, 45–66 Gy). Rates of significant Grade 3/4 hematologic toxicity were 38% and 7%, respectively. One patient experienced Grade 3 acute esophagitis, and 2 experienced late (Grade 3) esophageal stricture, successfully managed with dilation. One patient experienced Grade 3 pneumonitis. The overall response rate was 88%. One-year overall survival was 81%. Conclusions Full systemic dose pemetrexed seems to be safe with full-dose cisplatin and thoracic radiation in Stage IIIA/B NSCLC. Pemetrexed is the first third-generation cytotoxic agent tolerable at full dose in this setting. A Phase II study evaluating Dose Level 4 is ongoing.