Phase II study of S-1, a novel oral fluorophyrimidine derivative, in patients with metastatic colorectal carcinoma. S-1 Cooperative Colorectal Carcinoma Study Group.
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.
Ohtsu
A
A
Department of Gastrointestinal Oncology/Gastroenterology, National Cancer Center Hospital East, Kashiwa, Japan.
Baba
H
H
Sakata
Y
Y
Mitachi
Y
Y
Horikoshi
N
N
Sugimachi
K
K
Taguchi
T
T
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010094:Oxonic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D005641:Tegafur / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid