title: Phase I study of docetaxel, cisplatin and S-1 in patients with advanced gastric cancer.
abstract: OBJECTIVE
  S-1 plus cisplatin is standard treatment for advanced gastric cancer in Japan. Triplet therapy with docetaxel, cisplatin and fluoropyrimidine showed a survival benefit over doublet therapy, but was associated with substantial toxicities. We investigated the maximum tolerated dose of combination chemotherapy with divided-dose docetaxel added to standard-dose S-1 plus cisplatin in advanced gastric cancer patients.
  
  
  METHODS
  Patients with advanced gastric cancer, naive to chemotherapy or not refractory to fluoropyrimidine, were enrolled. Fixed doses of S-1 (40 mg/m(2) twice daily for 3 weeks) and cisplatin (60 mg/m(2) on day 1) were administered with increasing docetaxel dose levels of 20 mg/m(2) (dose level 1), 25 mg/m(2) (dose level 2) and 30 mg/m(2) (dose level 3) on days 1, 8 and 15, or 40 mg/m(2) (dose level 4) on days 1 and 15 of a 5-week cycle. Treatment cycles were repeated until disease progression, patient's refusal or unacceptable toxicity occurred.
  
  
  RESULTS
  Fifteen patients were enrolled. During the first cycle, no dose-limiting toxicity was observed at dose levels 1 and 2. At dose level 3, grade 3 febrile neutropenia was seen in one patient. At dose level 4, grade 3 infection and grade 3 abdominal pain were observed. Thus, dose level 4 was determined to be the maximum tolerated dose. The response rate was 54% (7/13), and median progression-free survival and overall survival were 243 and 383 days, respectively.
  
  
  CONCLUSIONS
  The recommended dose of docetaxel added to standard-dose S-1 (80 mg/m(2) days 1-21) plus cisplatin (60 mg/m(2) day 1) was 40 mg/m(2) on days 1 and 15 of a 5-week cycle.
authors.affiliation: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Japan. shironaka@ta2.so-net.ne.jp
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hironaka
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Keisei
authors.initials: K
authors.lastname: Taku
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yokota
authors.forename: Kohei
authors.initials: K
authors.lastname: Shitara
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.forename: Shinya
authors.initials: S
authors.lastname: Ueda
authors.forename: Nozomu
authors.initials: N
authors.lastname: Machida
authors.forename: Kei
authors.initials: K
authors.lastname: Muro
authors.forename: Narikazu
authors.initials: N
authors.lastname: Boku
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007564:Japan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D043823:Taxoids; C079198:S 1 (combination); D005641:Tegafur; D000077143:Docetaxel; D010094:Oxonic Acid; D002945:Cisplatin