title: S-1 plus irinotecan and oxaliplatin for the first-line treatment of patients with metastatic colorectal cancer: a prospective phase II study and pharmacogenetic analysis.
abstract: BACKGROUND
  S-1 is an oral fluoropyrimidine that mimics infusional 5-fluorouracil. The aim of this phase II trial was to explore the clinical efficacy of the triplet regimen TIROX, which consists of S-1, irinotecan and oxaliplatin.
  
  
  METHODS
  Forty-two chemo-naive patients with metastatic colorectal cancer (mCRC) were planned to be enrolled and be treated with irinotecan 150 mg m(-2) followed by oxaliplatin 85 mg m(-2) on day 1 and S-1 80 mg m(-2) per day from day 1 to 14 every 3 weeks. Polymorphisms in the UGT1A1, UGT1A6, UGT1A7 and CYP2A6 genes were analysed.
  
  
  RESULTS
  Between July 2007 and February 2008, 43 patients were enrolled. An objective response was noted in 29 patients (67.4%, 95% confidence interval: 53.4-81.4), of which 2 achieved durable complete responses. The median progression-free survival was 10.0 months and the median overall survival was 19.2 months. Significant grade 3 or 4 adverse events were neutropenia (45.2%), febrile neutropenia (9.5%), diarrhoea (7.1%) and vomiting (9.5%). Increased gastrointestinal toxicities were associated with the presence of UGT1A6*2 or UGT1A7*3 and an improved tumour response was noted in those without variant alleles of CYP2A6 or UGT1A1*60.
  
  
  CONCLUSIONS
  The combination of S-1, irinotecan and oxaliplatin showed favourable efficacy and tolerability in untreated patients with mCRC.
authors: Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769, Korea.
authors: S Y
authors: SY
authors: Kim
authors: Y
authors: Y
authors: S Hong
authors: E
authors: E
authors: K Shim
authors: S-Y
authors: SY
authors: Kong
authors: A
authors: A
authors: Shin
authors: J Y
authors: JY
authors: Baek
authors: K H
authors: KH
authors: Jung
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D065637:Cytochrome P-450 CYP2A6; D004338:Drug Combinations; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D014453:Glucuronosyltransferase; D002166:Camptothecin
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