Cetuximab plus gemcitabine-oxaliplatin (GEMOX) in patients with refractory advanced intrahepatic cholangiocarcinomas.
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.
Paule
Bernard
B
Hepato-Biliary Center, Assistance Publique-Hôpitaux de Paris, Hôpital Paul-Brousse, Faculté de Médecine Paris-Sud 11, Villejuif, France.
Herelle
Marie-Olga
MO
Rage
Estelle
E
Ducreux
Michel
M
Adam
René
R
Guettier
Catherine
C
Bralet
Marie-Pierre
MP
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
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D003841:Deoxycytidine; D000068818:Cetuximab