title: Cetuximab plus gemcitabine-oxaliplatin (GEMOX) in patients with refractory advanced intrahepatic cholangiocarcinomas.
abstract: OBJECTIVE
  To assess the efficacy and safety of cetuximab in the palliative treatment of patients with intrahepatic cholangiocarcinomas (CCA) unresponsive to first-line gemcitabine-oxaliplatin (GEMOX) pretreatment.
  
  
  METHODS
  Nine patients (mean age: 54 years) with recurrent or unresectable CCA (6 peripheral and 3 hilar CCA, histologically proven) resistant to GEMOX received cetuximab 400 mg/m2 on day 1 then 250 mg/m2 weekly combined with gemcitabine 1,000 mg/m2 on day 1 and oxaliplatin 85 mg/m2 on day 2, every 3 weeks. Immunohistochemical detection of epidermal growth factor receptor (EGFR) and erbB-2, as well as EGFR gene copy number were assessed. Tumor response was measured using RECIST.
  
  
  RESULTS
  A total of 43 cycles were given (3-8 per patient). After 6 months, CT scans revealed 1 complete response, 1 partial response, 1 stable disease and 6 patients with disease progression. Median time to tumor progression and overall survival were 4 and 7 months, respectively. All patients relapsed (mean follow-up: 17 months). In 6 patients, death was not related to treatment. Toxicity included grade 3 neutropenia (n = 1) and acne-like rash (n = 7). In 7 of the 9 patients, EGFR was highly expressed in all tumor cells without gene amplification. No expression of erbB-2 was noted.
  
  
  CONCLUSIONS
  Even in the absence of EGFR gene amplification, cetuximab + GEMOX is a well-tolerated palliative treatment in patients with advanced CCA. Adding cetuximab circumvents tumor resistance to GEMOX.
authors.affiliation: Hepato-Biliary Center, Assistance Publique-Hôpitaux de Paris, Hôpital Paul-Brousse, Faculté de Médecine Paris-Sud 11, Villejuif, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Paule
authors.forename: Marie-Olga
authors.initials: MO
authors.lastname: Herelle
authors.forename: Estelle
authors.initials: E
authors.lastname: Rage
authors.forename: Michel
authors.initials: M
authors.lastname: Ducreux
authors.forename: René
authors.initials: R
authors.lastname: Adam
authors.forename: Catherine
authors.initials: C
authors.lastname: Guettier
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Bralet
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068818:Cetuximab; D018281:Cholangiocarcinoma / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010166:Palliative Care
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D003841:Deoxycytidine; D000068818:Cetuximab