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https://hdl.handle.net/2440/93309
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Type: | Journal article |
Title: | Vascular endothelial growth factor D expression is a potential biomarker of bevacizumab benefit in colorectal cancer |
Author: | Weickhardt, A. Williams, D. Lee, C. Chionh, F. Simes, J. Murone, C. Wilson, K. Parry, M. Asadi, K. Scott, A. Punt, C. Nagtegaal, I. Price, T. Mariadason, J. Tebbutt, N. |
Citation: | British Journal of Cancer, 2015; 113(1):37-45 |
Publisher: | Nature Publishing Group |
Issue Date: | 2015 |
ISSN: | 0007-0920 1532-1827 |
Statement of Responsibility: | A J Weickhardt, D S Williams, C K Lee, F Chionh, J Simes, C Murone, K Wilson, M M Parry, K Asadi, A M Scott, C J A Punt, I D Nagtegaal, T J Price, J M Mariadason, and N C Tebbutt |
Abstract: | Background: Bevacizumab prolongs progression-free survival (PFS) in patients with metastatic colorectal cancer. We analysed the protein expression levels of vascular endothelial growth factor (VEGF) ligands and receptors to determine their prognostic and predictive effects. Methods: We graded expression of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-R1, and VEGF-R2 to assess whether overexpression predicted bevacizumab resistance in samples from 268 of 471 patients randomised to capecitabine (C), capecitabine and bevacizumab (CB), or CB and mitomycin (CBM) in the MAX trial and extended the analysis to the CAIRO-2 population. Results: Patients with low expression of VEGF-D (0, 1+) benefited from bevacizumab treatment (PFS hazard ratio (HR) (C vs CB+CBM), 0.21; 95% CI, 0.08–0.55; overall survival (OS) HR, 0.35; 95% CI, 0.13–0.90). Patients with higher VEGF-D expression received less benefit (VEGF-D 2+ PFS HR, 0.67; 95% CI, 0.45–1.00; OS HR, 0.82; 95% CI, 0.52–1.30; VEGF-D 3+ PFS HR, 0.77; 95% CI, 0.50–1.17; OS HR, 1.28; 95% CI, 0.79–2.09) (P interaction <0.05). In CAIRO-2, there was no difference in PFS or OS according to VEGF-D expression. Conclusions: The predictive value of VEGF-D expression for bevacizumab may depend on the chemotherapy backbone used. Further evaluation is required before clinical utilisation. |
Keywords: | bevacizumab; VEGF; colorectal cancer; biomarkers; prediction |
Rights: | © 2015 Cancer Research UK. All rights reserved |
DOI: | 10.1038/bjc.2015.209 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1037786 |
Published version: | http://dx.doi.org/10.1038/bjc.2015.209 |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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