title: Phase II study of a triplet regimen of S-1 combined with irinotecan and oxaliplatin in patients with metastatic gastric cancer: clinical and pharmacogenetic results.
abstract: BACKGROUND
  The aim of this study was to investigate the efficacy and safety of S-1/irinotecan/oxaliplatin (TIROX) in metastatic gastric cancer (MGC) and the association between treatment outcome and uridine diphosphate-glucuronosyltransferase (UGT) 1A polymorphisms.
  
  
  METHODS
  Patients with previously untreated MGC received S-1 40 mg/m(2) b.i.d. on days 1-14 and irinotecan 150 mg/m(2) plus oxaliplatin 85 mg/m(2) on day 1 every 3 weeks.
  
  
  RESULTS
  Forty-four patients were enrolled. In intent-to-treat analysis, the objective response rate was 75%, including the complete response (CR) rate of 14%. The median time to progression and overall survival was 10.2 and 17.6 months, respectively. Ten (26%) of the 39 patients with primary gastric tumor showed biopsy-confirmed gastric CR. Grade 3/4 neutropenia developed in 66% of patients and grade 3 febrile neutropenia in 16%. The most common grade 3 nonhematologic toxic effects were abdominal pain (18%), anorexia (16%), and diarrhea (14%). UGT1A polymorphisms were associated with significantly higher incidence of grade 4 leukopenia (UGT1A1*6), neutropenia (UGT1A1*6, UGT1A6*2, and UGT1A7*3), grade 3/4 febrile neutropenia (UGT1A1*6), and grade 3 abdominal pain (UGT1A1*6).
  
  
  CONCLUSIONS
  The TIROX regimen induced marked tumor reduction and promising survival with a manageable toxicity profile in MGC patients. UGT1A genotype may be predictive of TIROX toxicity.
authors.affiliation: Center for Gastric Cancer. Electronic address: sukryun73@hanmail.net.
authors.forename: S R
authors.initials: SR
authors.lastname: Park
authors.affiliation: Center for Clinical Services, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Kong
authors.affiliation: Center for Gastric Cancer.
authors.forename: J
authors.initials: J
authors.lastname: Rhee
authors.affiliation: Center for Gastric Cancer.
authors.forename: Y-I
authors.initials: YI
authors.lastname: Park
authors.affiliation: Center for Gastric Cancer.
authors.forename: K W
authors.initials: KW
authors.lastname: Ryu
authors.affiliation: Center for Gastric Cancer.
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Center for Gastric Cancer.
authors.forename: Y-W
authors.initials: YW
authors.lastname: Kim
authors.affiliation: Center for Gastric Cancer.
authors.forename: I J
authors.initials: IJ
authors.lastname: Choi
authors.affiliation: Center for Gastric Cancer.
authors.forename: C G
authors.initials: CG
authors.lastname: Kim
authors.affiliation: Center for Gastric Cancer.
authors.forename: J Y
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Center for Gastric Cancer.
authors.forename: S-J
authors.initials: SJ
authors.lastname: Cho
authors.affiliation: Center for Gastric Cancer.
authors.forename: N K
authors.initials: NK
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D014453:Glucuronosyltransferase; D002166:Camptothecin