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) pemetrexed (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 pemetrexed 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.