title: Phase I/II and pharmacokinetic study of S-1 and oxaliplatin in previously untreated advanced gastric cancer.
abstract: BACKGROUND
  We aimed to determine the maximum-tolerated dose (MTD) of S-1 when given with oxaliplatin, to evaluate S-1 pharmacokinetics, and to determine the efficacy and safety of this regimen as a first-line treatment for advanced gastric cancer (AGC).
  
  
  METHODS
  Oxaliplatin was fixed at a dose of 130 mg/m2 on day 1 (D1). S-1 was administered from D1 to D14 of a 3-week cycle, and escalated by 10 mg/m2 per day from 70 mg/m2 per day up to 100 mg/m2 per day. Pharmacokinetic analyses were performed following a single dose of S-1 on D-5 and D1 of the first cycle.
  
  
  RESULTS
  In phase I (n=18), MTD was not defined. In phase II (n=47) with the planned maximum dose, partial response was achieved in 26 patients (55.3%) and stable disease in 14 patients (29.8%). The median time to progression was 6.6 months (95% CI 4.0-9.2 months) and the median overall survival was 12.5 months (95% CI 9.2-15.9 months). Frequent grade 3/4 toxicities included thrombocytopenia (39%), neutropenia (28%), anemia (17%), and leukopenia (13%). There was one grade 5 febrile neutropenia during the first cycle.
  
  
  CONCLUSIONS
  The pharmacokinetics of S-1 was not influenced by oxaliplatin. S-1/Oxaliplatin combination therapy is highly active against AGC and has a favorable toxicity profile.
authors: Division of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 86 Asanbyeongwon-gil, Poongnap-dong, Songpa-gu, Seoul, 138-736, Korea.
authors: Inkeun
authors: I
authors: Park
authors: Jae-Lyun
authors: JL
authors: Lee
authors: Min-Hee
authors: MH
authors: Ryu
authors: Heung Moon
authors: HM
authors: Chang
authors: Tae-Won
authors: TW
authors: Kim
authors: Sun-Jin
authors: SJ
authors: Sym
authors: Sung Sook
authors: SS
authors: Lee
authors: Geundoo
authors: G
authors: Jang
authors: Changhoon
authors: C
authors: Yoo
authors: Kyun-Seop
authors: KS
authors: Bae
authors: Yoon-Koo
authors: YK
authors: Kang
mesh_terms: D000328:Adult; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid