The relationship between pemetrexed exposure (AUC) and clinical outcome in Japanese NSCLC patients

18041 Background: The efficacy of pemetrexed (PEM) 500 mg/m2 administered with vitamin B12 and folic acid (FS) has been established in previously treated NSCLC. The 500 mg/m2 dose is based on the MTD determined for PEM without FS. Recently completed phase I studies have shown the recommended dose of PEM single agent with FS to be 900–1,000 mg/m2. A randomized phase II study conducted in Japan (ASCO 2007) showed PEM 500 mg/m2 and 1,000 mg/m2 with FS to have similar efficacy for patients with 2nd and 3rd line NSCLC. PEM is renally excreted and a PK model characterizing the relationship between CrCL and PEM AUC has been previously established. The exposure response relationships (ERRs) between AUC and progression free survival (PFS), individual patient’ tumor response, and toxicity were explored in these analyses. Methods: Eligible patients had a histologic or cytologic diagnosis of NSCLC, had been previously treated by 1 or 2 chemotherapy regimens, and were randomized to 500 mg/m2 (N = 108 pts) or 1,000 mg/...