title: Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials.
abstract: OBJECTIVE
  Adjuvant systemic chemotherapy administered after surgical resection of colorectal cancer metastases may reduce the risk of recurrence and improve survival, but its benefit has never been demonstrated. Two phase III trials (Fédération Francophone de Cancérologie Digestive [FFCD] Trial 9002 and the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Clinical Trials Group/Gruppo Italiano di Valutazione Interventi in Oncologia [ENG] trial) used a similar design and showed a trend favoring adjuvant chemotherapy, but both had to close prematurely because of slow accrual, thus lacking the statistical power to demonstrate the predefined difference in survival. We report here a pooled analysis based on individual data from these two trials.
  
  
  METHODS
  After complete resection of colorectal liver or lung metastases, patients were randomly assigned to chemotherapy (CT arm; fluorouracil [FU] 400 mg/m(2) administered intravenously [IV] once daily plus dl-leucovorin 200 mg/m(2) [FFCD] x 5 days or FU 370 mg/m(2) plus l-leucovorin 100 mg/m(2) IV x 5 days [ENG] for six cycles at 28-day intervals) or to surgery alone (S arm).
  
  
  RESULTS
  A total of 278 patients (CT, n = 138; S, n = 140) were included in the pooled analysis. Median progression-free survival was 27.9 months in the CT arm as compared with 18.8 months in the S arm (hazard ratio = 1.32; 95% CI, 1.00 to 1.76; P = .058). Median overall survival was 62.2 months in the CT arm compared with 47.3 months in the S arm (hazard ratio = 1.32; 95% CI, 0.95 to 1.82; P = .095). Adjuvant chemotherapy was independently associated with both progression-free survival and overall survival in multivariable analysis.
  
  
  CONCLUSIONS
  This pooled analysis shows a marginal statistical significance in favor of adjuvant chemotherapy with an FU bolus-based regimen after complete resection of colorectal cancer metastases.
authors.affiliation: Hépato-Gastroentérologie et Oncologie Digestive, Hôpital Ambroise Paré, Boulogne, France. emmanuel.mitry@apr.aphp.fr
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mitry
authors.forename: Anthony L A
authors.initials: AL
authors.lastname: Fields
authors.forename: Harry
authors.initials: H
authors.lastname: Bleiberg
authors.forename: Roberto
authors.initials: R
authors.lastname: Labianca
authors.forename: Guillaume
authors.initials: G
authors.lastname: Portier
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Tu
authors.forename: Donato
authors.initials: D
authors.lastname: Nitti
authors.forename: Valter
authors.initials: V
authors.lastname: Torri
authors.forename: Dominique
authors.initials: D
authors.lastname: Elias
authors.forename: Chris
authors.initials: C
authors.lastname: O'Callaghan
authors.forename: Bernard
authors.initials: B
authors.lastname: Langer
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Martignoni
authors.forename: Olivier
authors.initials: O
authors.lastname: Bouché
authors.forename: Franck
authors.initials: F
authors.lastname: Lazorthes
authors.forename: Eric
authors.initials: E
authors.lastname: Van Cutsem
authors.forename: Laurent
authors.initials: L
authors.lastname: Bedenne
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Moore
authors.forename: Philippe
authors.initials: P
authors.lastname: Rougier
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary* / Q000601:surgery; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D015996:Survival Rate
chemical_list: D002955:Leucovorin; D005472:Fluorouracil