Phase II study of S-1, a novel oral fluorophyrimidine derivative, in patients with metastatic colorectal carcinoma. S-1 Cooperative Colorectal Carcinoma Study Group

Br J Cancer. 2000 Jul;83(2):141-5. doi: 10.1054/bjoc.2000.1236.


This study set out to evaluate, in patients with metastatic colorectal carcinoma, the efficacy and toxicity of S-1, which contains tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate, based on a biochemical modulation of 5-fluorouracil (5-FU) targeted at inhibition of dihydropyrimidine dehydrogenase (DPD). Sixty-three patients with measurable metastatic colorectal carcinoma were enrolled into the study. None of the patients had received prior chemotherapy except for adjuvant setting. S-1 was administered 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 progression, unaccepted toxicity, or patient refusal. Twenty-two (35%) of the 62 eligible patients achieved PR with a 95% confidence interval of 25-48%. Five of the 10 patients with a history of adjuvant chemotherapy achieved partial remission. The median survival time was 12 months. Major adverse reactions included myelosuppressive and gastrointestinal toxicities, though their incidence of grade 3 or 4 being 13% in neutropenia and less than 10% in the others. None of the 53 patients treated as outpatients required hospitalization due to adverse reactions: These results suggest that S-1 achieves similar responses to those of infusional 5-FU plus leucovorin and shows the potential of another biochemical modulation with easily manageable toxicity.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Drug Combinations
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Oxonic Acid / adverse effects
  • Oxonic Acid / therapeutic use*
  • Pyridines / adverse effects
  • Pyridines / therapeutic use*
  • Survival Rate
  • Tegafur / adverse effects
  • Tegafur / therapeutic use*
  • Treatment Outcome


  • Antimetabolites, Antineoplastic
  • Drug Combinations
  • Pyridines
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid