A phase I/II study of plevitrexed with nutritional vitamin supplementation in gastric cancer

4231 Background: Plevitrexed (Px) is a novel thymidylate synthase inhibitor (TSI) that is taken up via the α-folate receptor as well as the reduced folate carrier, but is non-polyglutamated within the cell, resulting pre-clinically in increased tumor targeting, less development of resistance, and less toxicity to normal tissues than other TSIs. Promising activity was observed in a previous Phase II gastric cancer study however hematological toxicity limited day 8 dosing. Methods: This phase I/II study will recruit cohorts of 10 patients with chemonaive gastric cancer to 65, 130 and 165 mg/sqm of Px given iv on days 1 and 8 of a 3 week cycle, with nutritional supplementation starting 7 days prior to Px with oral folic acid 400-1000μg daily and vitamin B12 1000μg im every 9 weeks. Px doses were selected based on previous safety and efficacy information. The highest tolerable dose will be expanded to 39 patients based on Simon Optimal Design (α 5%, β 80%) for a minimal response rate of 10% assuming a true re...