TY - JOUR
T1 - S0941
T2 - A phase 2 SWOG study of sorafenib and erlotinib in patients with advanced gallbladder carcinoma or cholangiocarcinoma
AU - El-Khoueiry, A. B.
AU - Rankin, C.
AU - Siegel, A. B.
AU - Iqbal, S.
AU - Gong, I. Y.
AU - Micetich, K. C.
AU - Kayaleh, O. R.
AU - Lenz, H. J.
AU - Blanke, C. D.
N1 - Funding Information:
This investigation was supported in part by the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, DHHS: CA32102, CA38926, CA46441, CA46282, CA37981, CA58882, CA58723, CA45807, CA35176, CA35090, CA63848, CA67575, CA20319, CA16385, CA35431, CA13612 and CA63844.
PY - 2014/2/18
Y1 - 2014/2/18
N2 - Background:Gallbladder cancers and cholangiocarcinomas make up a heterogenous group of tumours with a poor prognosis in advanced stages. On the basis of evidence of dysregulation of the epidermal growth factor receptor, vascular endothelial growth factor and mitogen-activated protein kinase pathways in biliary cancers, we performed a phase 2 trial of sorafenib and erlotinib in patients with advanced biliary cancers.Methods:Eligible patients were previously untreated in the advanced setting with adequate hepatic and bone marrow function. Sorafenib and erlotinib were administered continuously at 400 mg BID and 100 mg daily, respectively.Results:Thirty-four eligible patients were recruited. The study was terminated after the first stage of accrual owing to failure to meet the predetermined number of patients who were alive and progression free at 4 months. There were two unconfirmed partial responses (6%, 95% CI: 1-20%), with a median progression-free survival of 2 months (95% CI: 2-3), and median overall survival of 6 months (95% CI: 3-8 months). Grade 3 and 4 adverse events included hypertension, AST/ALT increase, bilirubin increase, diarrhoea, hypokalaemia, hypophosphatemia and rash.Conclusions:Despite compelling preclinical rationale, the combination of sorafenib and erlotinib does not have promising clinical activity in an unselected population of patients with biliary cancers. Improved patient selection based on tumour biology and molecular markers is critical for future evaluation of targeted therapies in this disease.
AB - Background:Gallbladder cancers and cholangiocarcinomas make up a heterogenous group of tumours with a poor prognosis in advanced stages. On the basis of evidence of dysregulation of the epidermal growth factor receptor, vascular endothelial growth factor and mitogen-activated protein kinase pathways in biliary cancers, we performed a phase 2 trial of sorafenib and erlotinib in patients with advanced biliary cancers.Methods:Eligible patients were previously untreated in the advanced setting with adequate hepatic and bone marrow function. Sorafenib and erlotinib were administered continuously at 400 mg BID and 100 mg daily, respectively.Results:Thirty-four eligible patients were recruited. The study was terminated after the first stage of accrual owing to failure to meet the predetermined number of patients who were alive and progression free at 4 months. There were two unconfirmed partial responses (6%, 95% CI: 1-20%), with a median progression-free survival of 2 months (95% CI: 2-3), and median overall survival of 6 months (95% CI: 3-8 months). Grade 3 and 4 adverse events included hypertension, AST/ALT increase, bilirubin increase, diarrhoea, hypokalaemia, hypophosphatemia and rash.Conclusions:Despite compelling preclinical rationale, the combination of sorafenib and erlotinib does not have promising clinical activity in an unselected population of patients with biliary cancers. Improved patient selection based on tumour biology and molecular markers is critical for future evaluation of targeted therapies in this disease.
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U2 - 10.1038/bjc.2013.801
DO - 10.1038/bjc.2013.801
M3 - Article
C2 - 24423918
AN - SCOPUS:84894332061
SN - 0007-0920
VL - 110
SP - 882
EP - 887
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 4
ER -