title: A phase I study of triplet combination chemotherapy of paclitaxel, cisplatin and S-1 in patients with advanced gastric cancer.
abstract: OBJECTIVE
  S-1 and cisplatin combination therapy is a standard regimen for patients with advanced gastric cancer in Japan. The primary objective of this study was to determine the maximum tolerated dose and dose-limiting toxicities of a triplet regimen adding paclitaxel to S-1 and cisplatin combination therapy.
  
  
  METHODS
  Patients with previously untreated metastatic or recurrent gastric cancer were enrolled. Patients received S-1 (40 mg/m(2) p.o., twice daily, on days 1-21 every 35 days), cisplatin (30 mg/m(2) divided, on days 1 and 15) and paclitaxel (divided on days 1 and 15). The starting dose of paclitaxel was 50 mg/m(2) (level 1); the dose was escalated to 60 (level 2), 70 (level 3) and 80 mg/m(2) (level 4) in a stepwise fashion. Dose-limiting toxicity was determined during the first treatment cycle.
  
  
  RESULTS
  Eighteen patients enrolled. During the first cycle, no dose-limiting toxicity was observed at dose levels 1 and 2. At dose level 3, one of the six patients had dose-limiting toxicity (one patient had grade 4 neutropenia) and at dose level 4, one of the six patients had dose-limiting toxicity (one patient had febrile neutropenia, hypoalbuminemia and fatigue of grade 3). The maximum tolerated dose was not reached at level 4; however, grade 3 hyponatremia and hypokalemia in two of the six patients occurred during the second treatment course at level 4. From the point of view of safety in the outpatient setting, the recommended dose of paclitaxel was determined at 70 mg/m(2). The overall response rate was 50%.
  
  
  CONCLUSIONS
  The recommended dose of paclitaxel added to S-1 (80 mg/m(2) days 1-21) plus cisplatin (30 mg/m(2) days 1 and 15) was 70 mg/m(2) on days 1 and 15 of a 5-week cycle.
authors.affiliation: Department of Surgery, NTT West Osaka Hospital, 2-6-40 Karasugatsuji, Tennojiku, Osaka 543-8922, Japan. y.kimura@mhc.west.ntt.co.jp
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kimura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Imamura
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Fujitani
authors.forename: Motohiro
authors.initials: M
authors.lastname: Imano
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Tokunaga
authors.forename: Masaki
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Kurokawa
authors.forename: Toshio
authors.initials: T
authors.lastname: Shimokawa
authors.forename: Hiroya
authors.initials: H
authors.lastname: Takiuchi
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Tsujinaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furukawa
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D034141:Hypoalbuminemia / Q000139:chemically induced; D007008:Hypokalemia / Q000139:chemically induced; D007010:Hyponatremia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D017239:Paclitaxel; D002945:Cisplatin