A randomized phase II study of 500 mg/m2 and 1,000 mg/m2 of pemetrexed in patients (pts) with locally advanced or metastatic non-small cell lung cancer (NSCLC) who had prior chemotherapy
7590 Background: Pemetrexed (Pem) 500 mg/m2 (Pem 500) is currently the standard treatment for pts with locally advanced or metastatic NSCLC who had prior chemotherapy. In a recent Japanese phase I study with full vitamin supplementation, 1,000 mg/m2 was determined as the recommended dose. This study was to determine if Pem 1,000 mg/m2 (Pem 1,000) could lead to a better treatment outcome with an acceptable toxicity profile compared with Pem 500 in pts with NSCLC in a 2nd or 3rd line setting. Methods: Pts with PS 0–2, measurable, Stage III/IV NSCLC, who had previously received 1 or 2 chemotherapy regimens, were randomized to receive either Pem 500 or Pem 1,000 on day 1 of a 21-day cycle. The primary endpoint was overall response rate (ORR) based on the RECIST. Secondary endpoints included progression-free survival (PFS), duration of response (DR) and toxicity profile. The planned total sample size for the study was 214 pts. Results: From October 2004 to March 2006, 244 pts were enrolled at 28 centers, 226 pts were randomized and treated, and 216 pts were evaluable for efficacy. Baseline patient characteristics (Pem 500/Pem 1,000: 108/108) were: Males 63%/64%; median age 62/62 years (total range: 26–74); PS 0–1 94%/94%; Stage IV 81%/80%. The median number of treatment cycles completed on both arms was 3 (range 1–20+ for Pem 500 and 1–15+ for Pem 1,000). 11% of the Pem 500 pts and 6% of the Pem 1,000 pts completed at least 10 cycles. ORRs were 18.5% (90% CI: 12.6%-25.8%) for Pem 500 and 14.8% (90% CI: 9.5%- 21.6%) for Pem 1,000, and the respective disease control (PR+SD) rates were 55.6% and 46.3%. Median PFS with Pem 500 and Pem 1,000 was 3.0 and 2.4 months and median DR was 4.7 and 3.8 months, respectively. Grade 4 toxicities observed in more than 1% of pts were neutropenia (3.5% with Pem 500, 3.6% with Pem 1,000) and decreased lymphocyte count (2.6%, 1.8%). One drug related death for interstitial lung disease was reported with Pem 500. Conclusions: Pem 1,000 as well as Pem 500 showed remarkable efficacy outcomes with tolerable toxicity. Since Pem 1,000 showed treatment outcomes similar to Pem 500, this study supports the use of Pem 500 for Japanese pts with NSCLC in a 2nd or 3rd line setting. [Table: see text]