Efficacy and safety of two doses of pemetrexed supplemented with folic acid and vitamin B12 in previously treated patients with non-small cell lung cancer

Purpose: The objective of this study was to evaluate the efficacy and safety of two doses of pemetrexed supplemented with folic acid and vitamin B-12 in pretreated Japanese patients with advanced non-small cell lung cancer (NSCLC). Experimental Design: Patients with an Eastern Cooperative Oncology Group performance status 0 to 2, stage III or IV, and who received previously one or two chemotherapy regimens were randomized to receive 500 mg/m(2) pemetrexed (P500) or 1,000 mg/m(2) pernetrexed (P1000) on day 1 every 3 weeks. The primary endpoint Was response rate. Results: Of the 216 patients evaluable for efficacy (108 in each arm), response rates were 18.5% (90% confidence interval, 12.6-25.8%) and 14.8% (90% confidence interval, 9.5-21.6%), median survival times were 16.0 and 12.6 months, 1-year survival rates were 59.2% and 53.7%, and median progression-free survival were 3.0 and 2.5 months for the P500 and P1000, respectively. Cox multiple regression analysis indicated that pernetrexed dose was not a significant prognostic factor. Drug-related toxicity Was generally tolerable for both doses; however, the safety profile of P500 showed generally milder toxicity. Main adverse drug reactions of severity grade 3 or 4 were neutrophil count decreased (20.2%) and alanine aminotransferase (glutamine pyruvic transaminase) increased (15.8%) in P500 and neutrophil count decreased (24.3%),WBC count decreased (20.7%), and lymphocyte count decreased (18.0%) in P1000. One drug-related death from interstitial lung disease occurred in the P500. Conclusion: P500 and P1000 are similarly active with promising efficacy and acceptable safety outcomes in pretreated patients with NSCLC. These results support the use of P500 as a second- and third-line treatment of NSCLC.