Phase II study of oral S-1 for treatment of metastatic colorectal carcinoma




The goal of the current study was to evaluate the objective response rate and toxicity associated with the oral fluoropyrimidine S-1 (a combination of tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate) in patients with previously untreated metastatic colorectal carcinoma.


Thirty-eight patients were enrolled in the study. S-1 was administered orally at a dose of 40 mg/m2 twice daily for 28 days, followed by a 14-day rest period. Treatment was repeated every 6 weeks unless disease progression was observed.


A combined total of 173 courses of S-1 were administered to the 38 enrolled patients. The median number of courses administered to a given patient was 3.5 (range, 1–18). Although no patient exhibited a complete response to treatment, 15 had partial responses (response rate, 39.5%; 95% confidence interval, 24.0–56.6%). In addition, 5 patients had minor responses, and 14 had stable disease. Four patients were found to have progressive disease after two courses of treatment. The median survival time was 358 days (95% confidence interval, 305–490 days), and the 1-year survival rate was 47.4%. The most common adverse reactions included myelosuppression and gastrointestinal toxicity; most cases involved Grade 1 or 2 toxicity, but Grade 3 toxicities (anemia [7.9% of patients], neutropenia [5.3% of patients], diarrhea [2.6% of patients], and abnormal bilirubin levels [7.9% of patients]) also were noted. Neither Grade 4 toxicity nor treatment-related death was observed during the study.


Orally administered S-1 is active against metastatic colorectal carcinoma and has an acceptable toxicity profile. This promising agent has the potential to become a valuable chemotherapeutic option. Cancer 2004. © 2004 American Cancer Society.