title: Combination phase I trial of a novel oral fluorouracil derivative S-1 with low-dose cisplatin for unresectable and recurrent gastric cancer (JFMC27-9902).
abstract: OBJECTIVE
  The Japanese Foundation for Multidisciplinary Treatment of Cancer conducted a Phase I study of a novel oral fluorouracil derivative, S-1, combined with a low dose of cisplatin in unresectable and recurrent gastric cancer.
  
  
  METHODS
  S-1 was administered orally at 80-120 mg/body/day, depending on body surface area. One course consisted of consecutive administration for 28 days followed by a rest of 14 days. Low-dose cisplatin was given i.v. on days 1-5, 8-12, 15-19, and 22-26 of each course. The dose escalation of cisplatin began with an initial dose of 1 mg/m(2)/day as level 1 and was stepped up to 2, 3, 4, and 6 mg/m(2)/day as level 2, 3, 4, and 5, respectively. The regimen was repeated for at least two courses.
  
  
  RESULTS
  A total of 24 patients was entered in the study. There was no treatment-related death. At level 5, consisting of 5 evaluable patients, dose-limiting toxicity was experienced as grade 3 appetite loss in 2 patients and grade 4 neutropenia in 1 patient. The maximum-tolerated dose of cisplatin was estimated to be 6 mg/m(2)/day. We decided on a recommended dose of cisplatin of 4 mg/m(2)/day because the dosage was one level under the maximum-tolerated dose. All 3 patients at level 4 showed partial response, suggesting promising clinical efficacy with this dosage. The serum concentration of cisplatin at level 4 was 918 +/- 92 ng/ml on day 26 of the first course.
  
  
  CONCLUSIONS
  S-1 with low-dose cisplatin may become an effective regimen with acceptable toxicity for gastric cancer.
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan. bunzo@med.osaka-cu.ac.jp
authors.forename: Bunzo
authors.initials: B
authors.lastname: Nakata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Mitachi
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsuji
authors.forename: Susumu
authors.initials: S
authors.lastname: Yamamitsu
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Shirasaka
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000633:toxicity*; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018579:Patient Selection; D012008:Recurrence; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D002945:Cisplatin; D005472:Fluorouracil