title: Phase I-II study of irinotecan hydrochloride combined with cisplatin in patients with advanced gastric cancer.
abstract: OBJECTIVE
  A dose-escalation study of irinotecan hydrochloride (CPT-11) combined with fixed-dose cisplatin was conducted to determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and objective response rate in patients with advanced gastric cancer.
  
  
  METHODS
  Twenty-four patients with or without prior chemotherapy were enrolled. All patients were assessable for toxicities and response. On day 1, CPT-11 was administered as a 90-minute intravenous (I.V.) infusion, which was followed 2 hours later by a 120-minute I.V. infusion of cisplatin 80 mg/m2. CPT-11 alone at the same dose was administered again on day 15. The treatment was repeated every 4 weeks until disease progression was observed. The initial dose of CPT-11 was 60 mg/m2, and was escalated in increments of 10 mg/m2 until severe or life-threatening toxicity was observed.
  
  
  RESULTS
  The MTD of this combination was CPT-11 80 mg/m2. At this dose level, 16.7% of patients (two of 12) had leukopenia of less than 1,000/microL, 66.7% (eight of 12) had neutropenia of less than 500/microL, and 16.7% (two of 12) had severe diarrhea of grade 4 during the first course. The dose-limiting toxicity was neutropenia. Ten patients achieved a partial response (PR), and the overall response rate was 41.7% among 24 patients (95% confidence interval, 21.9% to 61.4%).
  
  
  CONCLUSIONS
  The recommended dose and schedule is CPT-11 70 mg/m2 on days 1 and 15 and cisplatin 80 mg/m2 on day 1 every 4 weeks. This combination of CPT-11 and cisplatin, considered to be active against advanced gastric cancer with acceptable toxicity, should be further assessed in a phase II study.
authors.affiliation: Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Shirao
authors.forename: Y
authors.initials: Y
authors.lastname: Shimada
authors.forename: H
authors.initials: H
authors.lastname: Kondo
authors.forename: D
authors.initials: D
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Yamao
authors.forename: H
authors.initials: H
authors.lastname: Ono
authors.forename: T
authors.initials: T
authors.lastname: Yokoyama
authors.forename: H
authors.initials: H
authors.lastname: Fukuda
authors.forename: M
authors.initials: M
authors.lastname: Oka
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: A
authors.initials: A
authors.lastname: Ohtsu
authors.forename: N
authors.initials: N
authors.lastname: Boku
authors.forename: T
authors.initials: T
authors.lastname: Fujii
authors.forename: Y
authors.initials: Y
authors.lastname: Oda
authors.forename: K
authors.initials: K
authors.lastname: Muro
authors.forename: S
authors.initials: S
authors.lastname: Yoshida
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002945:Cisplatin / Q000008:administration & dosage; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin