Combining bevacizumab and chemoradiation in rectal cancer. Translational results of the AXEBeam trial.

Abstract

BACKGROUND:

This study characterises molecular effect of bevacizumab, and explores the relation of molecular and genetic markers with response to bevacizumab combined with chemoradiotherapy (CRT).

METHODS:

From a subset of 59 patients of 84 rectal cancer patients included in a phase II study combining bevacizumab with CRT, tumour and blood samples were collected before and during treatment, offering the possibility to evaluate changes induced by one dose of bevacizumab. We performed cDNA microarrays, stains for CD31/CD34 combined with α-SMA and CA-IX, as well as enzyme-linked immunosorbent assay (ELISA) for circulating angiogenic proteins. Markers were related with the pathological response of patients.

RESULTS:

One dose of bevacizumab changed the expression of 14 genes and led to a significant decrease in microvessel density and in the proportion of pericyte-covered blood vessels, and a small but nonsignificant increase in hypoxia. Alterations in angiogenic processes after bevacizumab delivery were only detected in responding tumours. Lower PDGFA expression and PDGF-BB levels, less pericyte-covered blood vessels and higher CA-IX expression were found after bevacizumab treatment only in patients with pathological complete response.

CONCLUSIONS:

We could not support the 'normalization hypothesis' and suggest a role for PDGFA, PDGF-BB, CA-IX and α-SMA. Validation in larger patient groups is needed.

• Authors: M Verstraete, A Debucquoy, J Dekervel, J van Pelt, C Verslype, E Devos, G Chiritescu, K Dumon, A D'Hoore, O Gevaert, X Sagaert, E Van Cutsem, K Haustermans
• Journal: British journal of cancer (Br J Cancer) Vol. 112 Issue 8 Pg. 1314-25 (Apr 14 2015) ISSN: 1532-1827 [Electronic] England
• PMID: 25867261 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Antibodies, Monoclonal, Humanized
• Biomarkers, Tumor
• Bevacizumab

Topics

• Adult
• Aged
• Angiogenesis Inhibitors (administration & dosage, pharmacology)
• Antibodies, Monoclonal, Humanized (administration & dosage, pharmacology)
• Bevacizumab
• Biomarkers, Tumor (blood, genetics)
• Chemoradiotherapy
• Clinical Trials, Phase II as Topic
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Male
• Middle Aged
• Oligonucleotide Array Sequence Analysis
• Rectal Neoplasms (blood, pathology, therapy)
• Translational Research, Biomedical
• Treatment Outcome