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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

Authors' Affiliations: ¹ Department of Internal Medicine, National Cancer Center Hospital, Tokyo, Japan; ² National Kyushu Cancer Center, Fukuoka, Japan; ³ Kinki University School of Medicine, Osakasayama, Japan; ⁴ National Cancer Center Hospital East, Kashiwa, Japan; ⁵ Shizuoka Cancer Center Hospital, Shizuoka, Japan; ⁶ Eli Lilly and Company, Oncology Platform Team, Indianapolis, Indiana; and ⁷ Eli Lilly Japan K.K., Lilly Research Laboratories Japan, Kobe, Japan

Requests for reprints: Yuichiro Ohe, Department of Internal Medicine, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. Phone: 81-3-3542-2511; Fax: 81-3-3542-7006; E-mail: yohe{at}ncc.go.jp.

Purpose: The objective of this study was to evaluate the efficacy and safety of two doses of pemetrexed supplemented with folic acid and vitamin B₁₂ 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/m² pemetrexed (P500) or 1,000 mg/m² 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.