title: Capecitabine versus 5-fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results from the X-ACT trial with analysis by age and preliminary evidence of a pharmacodynamic marker of efficacy.
abstract: BACKGROUND
  This multicenter randomized trial compared oral capecitabine with bolus i.v. 5-fluorouracil (5-FU)/folinic acid (FA) as adjuvant therapy for stage III colon cancer.
  
  
  METHODS
  Patients were assigned to 24 weeks of capecitabine 1250 mg/m(2) twice daily on days 1-14 every 3 weeks or 5-FU/FA (Mayo Clinic regimen). The primary end point was disease-free survival (DFS).
  
  
  RESULTS
  The intent-to-treat population received capecitabine (n = 1004) or 5-FU/FA (n = 983). With a median follow-up of 6.9 years, capecitabine was at least equivalent to 5-FU/FA in terms of DFS [hazard ratio (HR) = 0.88; 95% confidence interval (CI) 0.77-1.01] and overall survival (OS) (HR = 0.86; 95% CI 0.74-1.01); the 95% CI upper limits were significantly less than the predefined noninferiority margins of 1.20 (P < 0.0001) and 1.14 (P < 0.001), respectively. This pattern was maintained in all subgroups, including patients aged ≥ 70 years. Preplanned multivariate analyses showed that capecitabine had statistically significant beneficial effects on DFS (P = 0.021) and OS (P = 0.020) versus 5-FU/FA. A post hoc analysis suggested that the occurrence of hand-foot syndrome may be associated with better outcomes in capecitabine recipients.
  
  
  CONCLUSIONS
  Oral capecitabine is an effective alternative to bolus 5-FU/FA as adjuvant treatment of patients with stage III colon cancer with efficacy benefits maintained at 5 years and in older patients.
authors: University of Leeds and St James's Institute of Oncology Hospital, Leeds Cancer Research UK Centre, Leeds, UK. Electronic address: c.j.twelves@leeds.ac.uk.
authors: C
authors: C
authors: Twelves
authors: Department of Internal Medicine I, Medical University Vienna, Vienna, Austria.
authors: W
authors: W
authors: Scheithauer
authors: Department of Haematology and Medical Oncology, Box Hill Hospital, Melbourne, Australia.
authors: J
authors: J
authors: McKendrick
authors: Digestive Oncology Unit, Hôpital La Timone, Université de la Méditerranée, Marseille, France.
authors: J-F
authors: JF
authors: Seitz
authors: Perth Oncology, Mount Medical Centre, Perth, Australia.
authors: G
authors: G
authors: Van Hazel
authors: Department of Medical Oncology, Tom Baker Cancer Centre, Calgary, Canada.
authors: A
authors: A
authors: Wong
authors: Department of Medical Oncology, Hospital Clínico San Carlos, Madrid, Spain.
authors: E
authors: E
authors: Díaz-Rubio
authors: F. Hoffmann-La Roche Inc., Basel, Switzerland.
authors: F
authors: F
authors: Gilberg
authors: Department of Medical Oncology, University of Glasgow, Glasgow, UK.
authors: J
authors: J
authors: Cassidy
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000328:Adult; D000367:Age Factors; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000032:analysis / Q000378:metabolism*; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005500:Follow-Up Studies; D060831:Hand-Foot Syndrome / Q000175:diagnosis / Q000453:epidemiology; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010599:Pharmacokinetics; D010865:Pilot Projects; D011379:Prognosis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D054316:Biomarkers, Pharmacological; D003841:Deoxycytidine; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil