title: Phase I/II study of a 3-week cycle of irinotecan and S-1 in patients with advanced colorectal cancer.
abstract: The combination of an oral fluoropyrimidine derivative, S-1, and irinotecan is expected to be a promising regimen for advanced colorectal cancer. This study was performed to determine the maximum tolerated dose (MTD) and recommended dose (RD) of irinotecan combined with S-1 in a 3-week cycle regimen and to observe the safety and efficacy for patients with previously untreated advanced colorectal cancer. Eighty milligrams per m(2) of S-1 was given orally for 14 consecutive days and escalated doses of irinotecan were administered on days 1 and 8 every 3 weeks in the phase I trial. Forty patients were treated at the RD during the phase II trial. Forty-three patients were enrolled between February 2005 and March 2007. The dose-limiting toxicity was diarrhea and abdominal pain. The MTD of irinotecan was 100 mg/m(2) and the RD was determined to be 80 mg/m(2) of irinotecan combined with 80 mg/m(2) of S-1. The phase II trial showed that 22 of 40 patients achieved a complete or partial response and eight had stable disease. The overall response rate was 55.0%. The median progression-free survival time and median survival time were 6.7 and 21 months, respectively. There were no treatment-related deaths. The main toxicities were leukopenia, neutropenia, anorexia and diarrhea. This study suggests the combination of irinotecan and S-1 repeated every 3 weeks is tolerable and effective for patients with previously untreated advanced colorectal cancer.
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University, Fukuoka, Japan. hkusaba@intmed1.med.kyushu-u.ac.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kusaba
authors.forename: Taito
authors.initials: T
authors.lastname: Esaki
authors.forename: Kitaro
authors.initials: K
authors.lastname: Futami
authors.forename: Sinnosuke
authors.initials: S
authors.lastname: Tanaka
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Fujishima
authors.forename: Kenji
authors.initials: K
authors.lastname: Mitsugi
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ariyama
authors.forename: Risa
authors.initials: R
authors.lastname: Tanaka
authors.forename: Naoko
authors.initials: N
authors.lastname: Kinugawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueki
authors.forename: Rhuichi
authors.initials: R
authors.lastname: Mibu
authors.forename: Eishi
authors.initials: E
authors.lastname: Baba
authors.forename: Shuji
authors.initials: S
authors.lastname: Nakano
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D002166:Camptothecin