title: A phase I study of combination therapy of the oral fluorinated pyrimidine compound S-1 with low-dose cisplatin twice-a-week administration (JFMC27-9902 Step2) in patients with advanced gastric cancer using a continual reassessment method.
abstract: OBJECTIVE
  We conducted a Phase I study to evaluate the safety and efficacy of a combination of S-1 with semi-weekly low-dose cisplatin in patients with unresectable/recurrent gastric cancer to determine the recommended dose (RD) for a subsequent Phase II study.
  
  
  METHODS
  S-1 was administered orally at 80-120 mg/body/day based on body surface area. One cycle consisted of the consecutive administration of S-1 for 28 days followed by 14 days rest. Three dose levels, 7.5, 10, and 15 mg/m(2)/day, were set for cisplatin, which was administered twice-a-week for 4 weeks followed by 2 weeks of rest in each cycle. Dose-limiting toxicity (DLT) data were continually monitored to enable decisions regarding cisplatin dose escalation and deescalation based on a new dose-finding algorithm using a continual reassessment method (CRM). The CRM target toxicity level to estimate the RD was set at 20%.
  
  
  RESULTS
  Eight and five patients were treated at cisplatin dose levels of 10 and 15 mg/m(2)/day, respectively. Two DLTs occurred at both dose levels. On the basis of this data, the CRM estimated the RD to be 10 mg/m(2)/day of cisplatin. Three patients of eight patients treated with 10 mg/m(2)/day of cisplatin exhibited a confirmed partial response during the treatment period.
  
  
  CONCLUSIONS
  For future trials examining the safety and efficacy of daily S-1 with semi-weekly cisplatin in patients with unresectable/recurrent gastric cancer, we found a cisplatin RD of 10 mg/m(2)/day.
authors.affiliation: Program in Health and Community Medicine, Nagoya University Graduate School of Medicine, 65 Tsuruma-Cho, Showa-Ku, Nagoya 466-8550, Japan. smorita@med.nagoya-u.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Bunzo
authors.initials: B
authors.lastname: Nakata
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsuji
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Mitachi
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Shirasaka
authors.forename: Shigetoyo
authors.initials: S
authors.lastname: Saji
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000465:Algorithms; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D002277:Carcinoma / Q000188:drug therapy* / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D018579:Patient Selection; D012107:Research Design; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin