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.
Shirao
Kuniaki
K
Department of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan. kshirao@ncc.go.jp
Ohtsu
Atsushi
A
Takada
Hideho
H
Mitachi
Yasushi
Y
Hirakawa
Kosei
K
Horikoshi
Noboru
N
Okamura
Takeshi
T
Hirata
Koichi
K
Saitoh
Soh
S
Isomoto
Hiroharu
H
Satoh
Atsushi
A
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D015996:Survival Rate; D005641:Tegafur / Q000627:therapeutic use*; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid