Abstract
Malignancies in the upper gastrointestinal (UGI) tract are amongst the most aggressive cancers and only few treatment options exist. We have recently analysed data from a phase II trial where patients with UGI cancers were treated with erlotinib and bevacizumab. The combination therapy could not be recommended in an unselected population of patients with chemo-refractory UGI cancer. However, a subpopulation of patients did benefit from the therapy. In this prospectively planned biomarker study we investigated vascular endothelial growth factor A (VEGF-A), VEGF receptor 2 (VEGFR-2) and epidermal growth factor receptor (EGFR) by immunohistochemistry and KRAS mutation status detected by PCR as potential predictors of effect of therapy. High VEGF-A expression was correlated to longer overall survival (HR: 0.8, 95%CI: 0.7-0.9) and high VEGFR-2 expression to shorter progression free survival (HR: 1.4, 95%CI: 1.0-1.9). EGFR expression and KRAS mutation status were not correlated to response or survival. We conclude that VEGF-A and VEGFR-2 could potentially be predictive markers in patients with UGI cancers treated with erlotinib and bevacizumab.
Publication types
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Clinical Trial, Phase II
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Multicenter Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Antibodies, Monoclonal / therapeutic use*
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents / therapeutic use*
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Bevacizumab
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism*
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ErbB Receptors / metabolism
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Erlotinib Hydrochloride
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Female
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Gastrointestinal Neoplasms / drug therapy*
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Gastrointestinal Neoplasms / genetics
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Gastrointestinal Neoplasms / metabolism*
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Gastrointestinal Neoplasms / pathology
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Humans
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Male
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Middle Aged
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Mutation / genetics
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins p21(ras)
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Quinazolines / therapeutic use*
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Survival Analysis
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Treatment Outcome
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Vascular Endothelial Growth Factor A / metabolism
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Vascular Endothelial Growth Factor Receptor-2 / metabolism
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ras Proteins / genetics
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents
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Biomarkers, Tumor
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KRAS protein, human
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Proto-Oncogene Proteins
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Quinazolines
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Vascular Endothelial Growth Factor A
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Bevacizumab
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Erlotinib Hydrochloride
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ErbB Receptors
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Vascular Endothelial Growth Factor Receptor-2
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Proto-Oncogene Proteins p21(ras)
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ras Proteins