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

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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. The authors sought to evaluate the objective response rate and toxicity associated with the oral fluoropyrimidine drug S‐1, which contains tegafur, 5‐chloro‐2,4‐dihydroxypyridine, and potassium oxonate, in patients with previously untreated metastatic colorectal carcinoma. S‐1 was found to be active in this setting (response rate, 39.5%) and had an acceptable toxicity profile.