title: XELOX vs FOLFOX-4 as first-line therapy for metastatic colorectal cancer: NO16966 updated results.
abstract: BACKGROUND
  We report updated overall survival (OS) data from study NO16966, which compared capecitabine plus oxaliplatin (XELOX) vs 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX4) as first-line therapy in metastatic colorectal cancer.
  
  
  METHODS
  NO16966 was a randomised, two-arm, non-inferiority, phase III comparison of XELOX vs FOLFOX4, which was subsequently amended to a 2 × 2 factorial design with further randomisation to bevacizumab or placebo. A planned follow-up exploratory analysis of OS was performed.
  
  
  RESULTS
  The intent-to-treat (ITT) population comprised 2034 patients (two-arm portion, n=634; 2 × 2 factorial portion, n=1400). For the whole NO16966 study population, median OS was 19.8 months in the pooled XELOX/XELOX-placebo/XELOX-bevacizumab arms vs 19.5 months in the pooled FOLFOX4/FOLFOX4-placebo/FOLFOX4-bevacizumab arms (hazard ratio 0.95 (97.5% CI 0.85-1.06)). In the pooled XELOX/XELOX-placebo arms, median OS was 19.0 vs 18.9 months in the pooled FOLFOX4/FOLFOX4-placebo arms (hazard ratio 0.95 (97.5% CI 0.83-1.09)). FOLFOX4 was associated with more grade 3/4 neutropenia/granulocytopenia and febrile neutropenia than XELOX, and XELOX with more grade 3 diarrhoea and grade 3 hand-foot syndrome than FOLFOX4.
  
  
  CONCLUSIONS
  Updated survival data from study NO16966 show that XELOX is similar to FOLFOX4, confirming the primary analysis of progression-free survival. XELOX can be considered as a routine first-line treatment option for patients with metastatic colorectal cancer.
authors.affiliation: Institute of Cancer Sciences, Beatson Oncology Centre, 1053 Great Western Road, Glasgow G12 0YN, UK. j.cassidy@beatson.gla.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Cassidy
authors.forename: S
authors.initials: S
authors.lastname: Clarke
authors.forename: E
authors.initials: E
authors.lastname: Díaz-Rubio
authors.forename: W
authors.initials: W
authors.lastname: Scheithauer
authors.forename: A
authors.initials: A
authors.lastname: Figer
authors.forename: R
authors.initials: R
authors.lastname: Wong
authors.forename: S
authors.initials: S
authors.lastname: Koski
authors.forename: K
authors.initials: K
authors.lastname: Rittweger
authors.forename: F
authors.initials: F
authors.lastname: Gilberg
authors.forename: L
authors.initials: L
authors.lastname: Saltz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D010071:Oxaloacetates; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D003841:Deoxycytidine; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil