title: Correlation between the response to cetuximab alone or in combination with irinotecan and the activated/phosphorylated epidermal growth factor receptor in metastatic colorectal cancer.
abstract: Despite staining positive for the epidermal growth factor receptor (EGFR), a significant number of EGFR-expressing colorectal cancers are resistant to cetuximab, a chimeric monoclonal antibody directed against EGFR. Activation of EGFR through the autophosphorylation of its tyrosine residues stimulates different signaling downstream pathways and may reflect the level of receptor utilization by the tumor. This study investigated activated/phosphorylated EGFR (pEGFR) in 23 patients with EGFR-positive metastatic colorectal cancer refractory to irinotecan and treated with cetuximab, alone or in combination with irinotecan. Seven patients received cetuximab, and 16 patients received cetuximab plus irinotecan. Among the 23 patients, six (26%) had a partial response, 10 (44%) had stable disease, and seven (30%) had progressive disease. Median duration of disease control (partial response + stable disease) was 6 months. Nineteen out of 20 EGFR-positive tumors (95%) stained positive for pEGFR and had a median pEGFR immunohistochemical score of 5. Disease control rates differed between patients with a pEGFR immunohistochemical score >or= 7 (7/7, 100%) and less than 7 (7/13, 53.8%), showing a trend toward higher disease control in patients with high levels of pEGFR (>or= 7) who were treated with cetuximab with or without irinotecan (P = .05).
authors.affiliation: Jules Bordet Institute, Translational Research and Gastroenterology Unit, 1000 Brussels, Belgium. nic_personeni@hotmail.com
authors.forename: Nicola
authors.initials: N
authors.lastname: Personeni
authors.forename: Alain
authors.initials: A
authors.lastname: Hendlisz
authors.forename: Julien
authors.initials: J
authors.lastname: Gallez
authors.forename: Maria Gomez
authors.initials: MG
authors.lastname: Galdon
authors.forename: Denis
authors.initials: D
authors.lastname: Larsimont
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Van Laethem
authors.forename: Nathalie
authors.initials: N
authors.lastname: Nagy
authors.forename: Martine
authors.initials: M
authors.lastname: Barette
authors.forename: Marianne
authors.initials: M
authors.lastname: Paesmans
authors.forename: Fatima
authors.initials: F
authors.lastname: Cardoso
authors.forename: Harry
authors.initials: H
authors.lastname: Bleiberg
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D017322:Clinical Trials, Phase II as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D066246:ErbB Receptors / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000077146:Irinotecan; D066246:ErbB Receptors; D000068818:Cetuximab; D002166:Camptothecin