Hypertension as a predictive biomarker in bevacizumab treatment for colorectal cancer patients
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ORIGINAL PAPER
Hypertension as a predictive biomarker in bevacizumab treatment for colorectal cancer patients Esther Tahover • Beatrice Uziely • Azzam Salah Mark Temper • Tamar Peretz • Ayala Hubert
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Received: 24 July 2012 / Accepted: 31 July 2012 / Published online: 20 December 2012 Springer Science+Business Media New York 2012
Abstract Bevacizumab treatment is associated with an increased risk of hypertension (HTN), a potential marker for effectiveness. We aimed to assess whether grades 2–3 HTN during bevacizumab treatment was associated with increased overall survival (OS) or progression-free survival (PFS). One hundred and eighty-one patients with metastatic colorectal cancer (CRC), who were treated in our Department from January 2009–February 2011 were included. Bevacizumab was administered jointly with standard first- or second-line chemotherapy protocols. Blood pressure was measured before each treatment. HTN was graded using common toxicity criteria. There were 181 CRC patients. Grades 2–3 HTN developed in 81 patients (44.75 %) but not in 100 patients (55.25 %); no patient developed grades 4–5 HTN. Median follow-up was 15.2 months. HTN was associated with better OS in HTNpositive versus HTN-negative patients (median not reached vs. 36.8 months, p = 0.029) and better PFS (29.9 vs. 17.2 months, p = 0.024, respectively). Bevacizumab-related HTN may represent a biomarker for clinical benefit in metastatic colorectal cancer patients. Keywords Colorectal Cancer Bevacizumab Vascular endothelial growth factor HTN
E. Tahover and B. Uziely contributed equally to this work. E. Tahover (&) B. Uziely A. Salah M. Temper T. Peretz A. Hubert Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, POB 12000, Jerusalem 91120, Israel e-mail: [email protected]
Introduction Vascular endothelial growth factor (VEGF) activates the major pathways involved in tumor angiogenesis. It causes endothelial cell survival, migration, and permeability, and stimulates the growth of blood vessels that feed the tumor. Antineoplastic agents targeting VEGF have been developed in the last few years as part of a novel therapeutic approach targeting biological pathways of tumor cells. Bevacizumab is a recombinant, humanized monoclonal antibody that blocks activation of tumor receptors for VEGF. It has been shown in randomized trials to improve progression-free survival (PFS) and overall survival (OS) when combined with standard first- [1, 2] and second-line [3] chemotherapy protocols in metastatic colorectal cancer (CRC). Treatment with bevacizumab has also shown improvement in PFS and or OS when used in breast cancer and non-small cell lung cancer when combined with chemotherapy regimens. Bevacizumab has a favorable safety profile. The most common side effect of bevacizumab is hypertension (HTN), which is usually managed by standard oral hypertensive medications and rarely requires discontinuation of oncology treatments. The incidence of HTN in a meta-analysis of studies including patients with a
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