title: Phase I study of S-1 combined with irinotecan (CPT-11) in patients with advanced gastric cancer (OGSG 0002).
abstract: OBJECTIVE
  A dose-escalation study of irinotecan (CPT-11) combined with S-1, a novel oral fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD) and dose-limiting toxicities (DLTs) in advanced gastric cancer.
  
  
  METHODS
  S-1 was administered orally at 80 mg/m(2)/day for 21 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 40 mg/m(2)/day, stepping up to 60, 80, 100 or 120 mg/m(2)/day depending on the DLT. Courses were repeated every 5 weeks, unless disease progression or severe toxicity was observed. At a level of the RD, five patients were added to conduct a pharmacokinetic (PK) study.
  
  
  RESULTS
  A total of 24 patients were entered in this study. The MTD of CPT-11 was considered to be 100 mg/m(2), because 50% of the patients (3/6) developed DLTs, diarrhea and rash. Therefore, the RD of CPT-11 was set at the dose immediately below 80 mg/m(2). The overall response rate (RR) by the criteria of the Japanese Research Society of Gastric Cancer was 58.3% (14/24) and the RR at the RD was 66.7% (6/9), suggesting promising clinical efficacy. There were no significant differences between the PK parameters of S-1 on days 10 and 15.
  
  
  CONCLUSIONS
  S-1 with CPT-11 can be combined safely without CPT-11 effect on S-1 PK data and holds promise as an effective regimen for advanced gastric cancer.
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan. in2028@poh.osaka-med.ac.jp
authors.forename: Hiroya
authors.initials: H
authors.lastname: Takiuchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Narahara
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Tsujinaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Gotoh
authors.forename: Sei-ichiro
authors.initials: S
authors.lastname: Kawabe
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Katsu
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Iishi
authors.forename: Masaharu
authors.initials: M
authors.lastname: Tatsuta
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Fujitani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furukawa
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Taguchi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004338:Drug Combinations; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D002166:Camptothecin