title: Performance of outpatient regimen of S-1 in combination with fractional cisplatin for advanced or recurrent gastric cancers: a phase I study.
abstract: BACKGROUND
  We designed an outpatient regimen consisting of fractional cisplatin in combination with S-1, a novel oral fluoropyrimidine derivative for the treatment of recurrent or advanced gastric cancer and conducted a phase I study to determine the dose limiting toxicities (DLTs) and recommended dose (RD).
  
  
  METHODS
  Escalating dosages of cisplatin (15, 20, and 25 mg/m(2), as levels 1, 2, and 3, respectively) were administered over 2 h on days 1, 8, and 15, with a fixed dose of S-1 for 3 consecutive weeks (days 1-21), repeated every 5 weeks. National Cancer Institute common toxicity criteria(NCI-CTC) grade 2 toxicities required treatment delay. Primary first cycle DLTs were defined as NCI-CTC grade 3 or 4 toxicities (except for hemoglobin levels, nausea, and vomiting).
  
  
  RESULTS
  Nine patients were initially enrolled, and DLTs did not appear; however, one level-3 patient experienced grade 3 anemia. An additional three patients were enrolled in level 3 to confirm the toxicity profiles, and none experienced DLTs. Toxicity evaluations throughout a total of 62 cycles revealed that grade 1 or 2 hematological toxicities were common, although mostly transient, with recovery without specific treatment. One patient each in levels 1 and 3 required hospitalization due to grade 3 toxicities in the later cycles. Mean dose intensities for S-1 and cisplatin were both more than 91%. There were no treatment-related deaths. The preliminary response rate was 44%.
  
  
  CONCLUSIONS
  It was concluded that the RD of cisplatin in this regimen was 25 mg/m(2) (level 3). S-1 in combination with fractional cisplatin is a promising regimen that allows repeated drug administration, in an outpatient setting, for advanced or recurrent gastric cancers. A phase II study of the RD is now under way.
authors.affiliation: Department of Gastrointestinal Surgery, University of Tokyo, 7-3-1 Hongo, Tokyo 113-8655, Japan. shimoyama-dis@h.u-tokyo.ac.jp
authors.forename: Shouji
authors.initials: S
authors.lastname: Shimoyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Imamura
authors.forename: Naoki
authors.initials: N
authors.lastname: Hiki
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Mafune
authors.forename: Michio
authors.initials: M
authors.lastname: Kaminishi
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010094:Oxonic Acid / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000556:secondary; D005641:Tegafur / Q000008:administration & dosage
chemical_list: D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin