title: A phase I study of sorafenib in combination with S-1 plus cisplatin in patients with advanced gastric cancer.
abstract: BACKGROUND
  Sorafenib inhibits several receptor tyrosine kinases involved in tumor progression and angiogenesis. S-1, an oral fluorouracil antitumor drug, plus cisplatin (CDDP) is the standard regimen for advanced gastric adenocarcinoma (AGC) in Japan. The purpose of this phase I study was to evaluate the safety, pharmacokinetics, and preliminary efficacy of sorafenib in combination with S-1 plus CDDP.
  
  
  METHODS
  Patients with histologically confirmed previously untreated AGC were evaluated for eligibility and treated with sorafenib (400 mg bid, days 1-35), S-1 (40 mg/m(2) bid, days 1-21), and CDDP (60 mg/m(2), day 8). Treatment was continued until disease progression or unacceptable toxicity. Pharmacokinetics for sorafenib, 5-FU, and CDDP were investigated in cycle 1.
  
  
  RESULTS
  Thirteen patients were enrolled and received at least one dose of the study treatment. No specific or serious adverse event was newly reported in this study. Five patients had partial response and 8 had stable disease as the best response. Pharmacokinetic analysis showed no significant differences in the exposures of sorafenib when administered alone or in combination with S-1 and CDDP.
  
  
  CONCLUSIONS
  The present phase I study demonstrates the acceptable toxicity and preliminary efficacy of combined treatment with S-1, CDDP, and sorafenib.
authors.affiliation: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan, yayamada@ncc.go.jp.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Naomi
authors.initials: N
authors.lastname: Kiyota
authors.forename: Nozomu
authors.initials: N
authors.lastname: Fuse
authors.forename: Ken
authors.initials: K
authors.lastname: Kato
authors.forename: Hironobu
authors.initials: H
authors.lastname: Minami
authors.forename: Kensei
authors.initials: K
authors.lastname: Hashizume
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kuroki
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ito
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D010349:Patient Compliance; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077157:Sorafenib; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D010671:Phenylurea Compounds; C079198:S 1 (combination); D005641:Tegafur; D009536:Niacinamide; D010094:Oxonic Acid; D000077157:Sorafenib; D002945:Cisplatin; D005472:Fluorouracil