A phase I study of combination therapy with S-1 and irinotecan (CPT-11) in patients with advanced colorectal cancer.
OBJECTIVE
The aim of this study was to determine the maximum tolerated dose, recommended dose and dose-limiting toxicities of irinotecan (CPT-11) plus S-1 in advanced colorectal cancer.


METHODS
S-1 was administered orally at 80 mg/m(2) per day for 14 consecutive days followed by a 2-week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at an initial dose of 80 mg/m(2) per day, stepping up to 100, 120 or 150 mg/m(2) per day. Courses were repeated every 4 weeks, unless disease progression or severe toxicities were observed.


RESULTS
A total of 21 patients were entered in this study. The maximum tolerated dose of CPT-11 was considered to be 150 mg/m(2), because 2 of 3 patients developed dose-limiting toxicities such as leukopenia, neutropenia, diarrhea and anorexia. The recommend dose of CPT-11 was set at 120 mg/m(2). Tumor response rate was 42.8% and median progression-free survival time was 10 months (95% confidential interval, 6.0-14.0 months).


CONCLUSIONS
A combination of S-1 and CPT-11 showed a good safety profile and can be recommended for further phase II studies in patients with colorectal cancer.
Shiozawa
Manabu
M
Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 1-1-2, Nakao, Asahi-ku, Yokohama, 241-0815, Japan. shiozawam@kcch.jp
Sugano
Nobuhiro
N
Tsuchida
Kazuhito
K
Morinaga
Soichiro
S
Akaike
Makoto
M
Sugimasa
Yukio
Y
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000633:toxicity; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000633:toxicity; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000633:toxicity*; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D005641:Tegafur / Q000633:toxicity*
D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D002166:Camptothecin