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

Abstract

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.

• Authors: Kuniaki Shirao, Atsushi Ohtsu, Hideho Takada, Yasushi Mitachi, Kosei Hirakawa, Noboru Horikoshi, Takeshi Okamura, Koichi Hirata, Soh Saitoh, Hiroharu Isomoto, Atsushi Satoh
• Journal: Cancer (Cancer) Vol. 100 Issue 11 Pg. 2355-61 (Jun 01 2004) ISSN: 0008-543X [Print] United States
• PMID: 15160338 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2004 American Cancer Society.

Chemical References

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

Topics

• Adenocarcinoma (drug therapy, secondary)
• Administration, Oral
• Adult
• Aged
• Antimetabolites, Antineoplastic (therapeutic use)
• Colorectal Neoplasms (drug therapy, pathology)
• Drug Combinations
• Female
• Humans
• Male
• Middle Aged
• Oxonic Acid (therapeutic use)
• Pyridines (therapeutic use)
• Survival Rate
• Tegafur (therapeutic use)
• Treatment Outcome