title: Cetuximab shows activity in colorectal cancer patients with tumors for which FISH analysis does not detect an increase in EGFR gene copy number.
abstract: BACKGROUND
  EGFR (epidermal growth factor receptor) gene gain assessed by FISH (fluorescence in situ hybridization) has been shown to be predictive of response to EGFR-targeted therapies in patients with non-small cell lung cancer. The aim or our study was to relate the EGFR gene copy number to therapeutic results in patients with metastatic colorectal cancer (CRC) treated with a cetuximab-containing regimen.
  
  
  METHODS
  Forty-seven patients with metastatic CRC treated with a cetuximab-containing regimen between August 2004 and September 2006 were included in our study. EGFR status was assessed by immunohistochemistry (IHC) and by FISH on fixed paraffin-embedded sections of tumor specimens.
  
  
  RESULTS
  By IHC (n = 47), 39 patients (83%) had EGFR-positive tumors. EGFR gene copy gain was detected in 8 (19.5%) of 41 tumors. Neither EGFR expression assessed by IHC nor EGFR gene copy gain assessed by FISH were statistically significantly correlated with objective response rate, disease control rate, progression-free survival, and overall survival. Of the 33 patients whose tumors were FISH negative, 8 patients (24.2%) had a partial response, and 10 (30.3%) had stable disease.
  
  
  CONCLUSIONS
  EGFR FISH analysis does not seem to be a sufficiently robust test for selecting candidate CRC patients for cetuximab therapy.
authors.affiliation: Department of Medical Oncology, Centre Antoine-Lacassagne, Canceropôle PACA, Nice, France. antoine.italiano@unice.fr
authors.forename: Antoine
authors.initials: A
authors.lastname: Italiano
authors.forename: Philippe
authors.initials: P
authors.lastname: Follana
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Caroli
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Badetti
authors.forename: Daniel
authors.initials: D
authors.lastname: Benchimol
authors.forename: Georges
authors.initials: G
authors.lastname: Garnier
authors.forename: Jean
authors.initials: J
authors.lastname: Gugenheim
authors.forename: Juliette
authors.initials: J
authors.lastname: Haudebourg
authors.forename: Frédérique
authors.initials: F
authors.lastname: Keslair
authors.forename: Gérard
authors.initials: G
authors.lastname: Lesbats
authors.forename: Gérard
authors.initials: G
authors.lastname: Lledo
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Roussel
authors.forename: Florence
authors.initials: F
authors.lastname: Pedeutour
authors.forename: Eric
authors.initials: E
authors.lastname: François
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab