A phase I study of pemetrexed (LY231514) supplemented with folate and vitamin B12 in Japanese patients with solid tumours.

The purpose of this study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of pemetrexed with folate and vitamin B12 supplementation (FA/VB(12)) in Japanese patients with solid tumours and to investigate the safety, efficacy, and pharmacokinetics of pemetrexed. Eligible patients had incurable solid tumours by standard treatments, a performance status 0-2, and adequate organ function. Pemetrexed from 300 to 1,200 mg m(-2) was administered as a 10-min infusion on day 1 of a 21-day cycle with FA/VB(12). Totally, 31 patients were treated. Dose-limiting toxicities were alanine aminotransferase (ALT) elevation at 700 mg m(-2), and infection and skin rash at 1,200 mg m(-2). The MTD/RD were determined to be 1,200/1,000 mg m(-2), respectively. The most common grade 3/4 toxicities were neutropenia (grade (G) 3:29, G4:3%), leucopenia (G3:13, G4:3%), lympopenia (G3:13%) and ALT elevation (G3:13%). Pemetrexed pharmacokinetics in Japanese were not overtly different from those in western patients. Partial response was achieved for 5/23 evaluable patients (four with non-small cell lung cancer (NSCLC) and one with thymoma). The MTD/RD of pemetrexed were determined to be 1,200/1,000 mg m(-2), respectively, that is, a higher RD than without FA/VB(12) (500 mg m(-2)). Pemetrexed with FA/VB(12) showed a tolerable toxicity profile and potent antitumour activity against NSCLC in this study.