title: Survival of patients with initially unresectable colorectal liver metastases treated with FOLFOX/cetuximab or FOLFIRI/cetuximab in a multidisciplinary concept (CELIM study).
abstract: BACKGROUND
  Initially, unresectable colorectal liver metastases can be resected after response to chemotherapy. While cetuximab has been shown to increase response and resection rates, the survival outcome for this conversion strategy needs further evaluation.
  
  
  METHODS
  Patients with technically unresectable and/or ≥5 liver metastases were treated with FOLFOX/cetuximab (arm A) or FOLFIRI/cetuximab (arm B) and evaluated with regard to resectability every 2 months. Tumour response and secondary resection data have been reported previously. A final analysis of overall survival (OS) and progression-free survival (PFS) was carried out in December 2012.
  
  
  RESULTS
  Between December 2004 and March 2008, 56 patients were randomised to arm A, 55 to arm B. The median OS was 35.7 [95% confidence interval (CI) 27.2-44.2] months [arm A: 35.8 (95% CI 28.1-43.6), arm B: 29.0 (95% CI 16.0-41.9) months, HR 1.03 (95% CI 0.66-1.61), P = 0.9]. The median PFS was 10.8 (95% CI 9.3-12.2) months [arm A: 11.2 (95% CI 7.2-15.3), arm B: 10.5 (95% CI 8.9-12.2) months, HR 1.18 (95% CI 0.79-1.74), P = 0.4]. Patients who underwent R0 resection (n = 36) achieved a better median OS [53.9 (95% CI 35.9-71.9) months] than those who did not [21.9 (95% CI 17.1-26.7) months, P < 0.001]. The median disease-free survival for R0 resected patients was 9.9 (95% CI 5.8-14.0) months, and the 5-year OS rate was 46.2% (95% CI 29.5% to 62.9%).
  
  
  CONCLUSIONS
  This study confirms a favourable long-term survival for patients with initially sub-optimal or unresectable colorectal liver metastases who respond to conversion therapy and undergo secondary resection. Both FOLFOX/FOLFIRI plus cetuximab, appear to be appropriate regimens for 'conversion' treatment in patients with K-RAS codon 12/13/61 wild-type tumours. Thus, liver surgery can be considered curative or alternatively as an additional 'line of therapy' in those patients who are not cured.
  
  
  BACKGROUND
  NCT00153998, www.clinicaltrials.gov.
authors.affiliation: University Cancer Center/Medical Department I, University Hospital Carl Gustav Carus, Dresden, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Folprecht
authors.forename: T
authors.initials: T
authors.lastname: Gruenberger
authors.forename: W
authors.initials: W
authors.lastname: Bechstein
authors.forename: H-R
authors.initials: HR
authors.lastname: Raab
authors.forename: J
authors.initials: J
authors.lastname: Weitz
authors.forename: F
authors.initials: F
authors.lastname: Lordick
authors.forename: J T
authors.initials: JT
authors.lastname: Hartmann
authors.forename: J
authors.initials: J
authors.lastname: Stoehlmacher-Williams
authors.forename: H
authors.initials: H
authors.lastname: Lang
authors.forename: T
authors.initials: T
authors.lastname: Trarbach
authors.forename: T
authors.initials: T
authors.lastname: Liersch
authors.forename: D
authors.initials: D
authors.lastname: Ockert
authors.forename: D
authors.initials: D
authors.lastname: Jaeger
authors.forename: U
authors.initials: U
authors.lastname: Steger
authors.forename: T
authors.initials: T
authors.lastname: Suedhoff
authors.forename: A
authors.initials: A
authors.lastname: Rentsch
authors.forename: C-H
authors.initials: CH
authors.lastname: Köhne
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D016016:Proportional Hazards Models; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: cetuximab; chemotherapy; colorectal cancer; liver metastases; multidisciplinary treatment; resection