Phase II study of S-1, a novel oral fluoropyrimidine derivative, in patients with metastatic colorectal carcinoma

This study set out to evaluate, in patients with metastatic colorectal carc inoma, the efficacy and toxicity of S-1, which contains tegafur, 5-chloro-2 ,4-dihydroxypyridine (CDHP) and potassium oxonate, based on a biochemical m odulation of 5-fluorouracil (5-FU) targeted at inhibition of dihydropyrimid ine dehydrogenase (DPD). Sixty-three patients with measurable metastatic co lorectal carcinoma were enrolled into the study. None of the patients had r eceived prior chemotherapy except for adjuvant setting. S-l was administere d orally twice daily at a standard dose of 80 mg m(-2) day(-1) for 28 days followed by a 14-day rest. This agent is continued until disease progressio n, unaccepted toxicity, or patient refusal. Twenty-two (35%) of the 62 elig ible patients achieved PR with a 95% confidence interval of 25-48%. Five of the 10 patients with a history of adjuvant chemotherapy achieved partial r emission. The median survival time was 12 months. Major adverse reactions i ncluded myelosuppressive and gastrointestinal toxicities, though their inci dence of grade 3 or 4 being 13% in neutropenia and less than 10% in the oth ers. None of the 53 patients treated as outpatients required hospitalizatio n due to adverse reactions: These results suggest that S-l achieves similar responses to those of infusional 5-FU plus leucovorin and shows the potent ial of another biochemical modulation with easily manageable toxicity. (C) 2000 Cancer Research Campaign.