title: Phase I/II study of irinotecan (CPT-11) and S-1 in the treatment of advanced gastric cancer.
abstract: A phase I/II study to determine the recommended dose for combination therapy with CPT-11 (irinotecan hydrochloride) and S-1 (tegafur, gimestat and otastat potassium) for advanced or recurrent gastric cancer, and to assess the safety and efficacy of this therapy. In the phase I portion of the study, S-1 was administered from day 1 to 14 at a fixed dose approved in Japan (80 mg/m2/day), and CPT-11 was administered on days 1 and 8, with its dose being escalated to 100 from 80 mg/m2. This regimen was repeated at 3-week intervals. The phase II portion of the study assessed the efficacy and safety of this regimen at the recommended dose determined in the phase I portion of the study. Seven patients were enrolled in the phase I portion of the study. The dose-limiting toxicity was the delay of administration owing to adverse reactions (leucopenia and diarrhea). The maximum tolerated dose of CPT-11 was 100 mg/m2 and the recommended dose was determined to be 80 mg/m2. In the phase II portion of the study, 10 patients with no prior chemotherapy regimen were enrolled. The median number of treatment cycles given was 4.5, the response rate was 20.0% (2/10) in all patients, the tumor control rate stable disease or better response was 60% (6/10) and the mean survival time was 311 days. Major adverse reactions included a decreased hemoglobin level, diarrhea, nausea and anorexia of grade 3 or worse (each occurred in 10% of the patients). Other adverse reactions were slight and well tolerated. The present combination therapy with CPT-11 and S-1 produced a low response rate but a high tumor control rate (stable disease or better response) and slight prolongation of survival time. This is a well-tolerated ambulatory regimen for advanced gastric cancer.
authors.affiliation: Department of Surgery, Tokyo Women's Medical University Medical Center East, and Center for Comprehensive and Advanced Medicine, Keio University Hospital, Tokyo, Japan. katsusu@dnh.twmu.ac.jp
authors.forename: Takao
authors.initials: T
authors.lastname: Katsube
authors.forename: Kenji
authors.initials: K
authors.lastname: Ogawa
authors.forename: Wataru
authors.initials: W
authors.lastname: Ichikawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Fujii
authors.forename: Akira
authors.initials: A
authors.lastname: Tokunaga
authors.forename: Yuh
authors.initials: Y
authors.lastname: Takagi
authors.forename: Misugu
authors.initials: M
authors.lastname: Kochi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kubota
authors.forename: Keisuke
authors.initials: K
authors.lastname: Aiba
authors.forename: Kuniyoshi
authors.initials: K
authors.lastname: Arai
authors.forename: Masanori
authors.initials: M
authors.lastname: Terashima
authors.forename: Masaki
authors.initials: M
authors.lastname: Kitajima
mesh_terms: D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage
chemical_list: D000932:Antiemetics; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D005641:Tegafur; D000077146:Irinotecan; D002166:Camptothecin