Copyright
©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Total and not bevacizumab-bound vascular endothelial growth factor as potential predictive factors to bevacizumab-based chemotherapy in colorectal cancer
Amalia Azzariti, Letizia Porcelli, Oronzo Brunetti, Marzia Del Re, Vito Longo, Patrizia Nardulli, Michele Signorile, Jian-Ming Xu, Angela Calabrese, Anna Elisa Quatrale, Evaristo Maiello, Vito Lorusso, Nicola Silvestris
Amalia Azzariti, Letizia Porcelli, Michele Signorile, Anna Elisa Quatrale, Clinical and Preclinical Pharmacology Laboratory, National Cancer Research Centre Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy
Oronzo Brunetti, Vito Lorusso, Nicola Silvestris, Medical Oncology Unit, National Cancer Research Centre Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy
Marzia Del Re, Clinical Pharmacology and Pharmacogenetics Unit, Department of Clinical and Experimental Medicine University Hospital, 56126 Pisa, Italy
Patrizia Nardulli, Pharmacology Unit, National Cancer Research Centre Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy
Jian-Ming Xu, Department of Gastrointestinal Oncology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing 100071, China
Angela Calabrese, Radiology unit, National Cancer Research Centre Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy
Evaristo Maiello, Medical Oncology Unit, “Casa Sollievo della Sofferenza” Hospital, 71013 San Giovanni Rotondo, Italy
Vito Longo, Medical Oncology Unit, “Mons R Dimiccoli” Hospital, 76121 Barletta, Italy
Author contributions: Azzariti A, Porcelli L, Brunetti O, and Quatrale AE make substantial contributions to conception and design, and/or acquisition of data, and/or analysis and interpretation of data; Del Re M, Longo V, Nardulli P, Xu JM, Maiello E, Lorusso V and Silvestris N participate in drafting the article or revising it critically for important intellectual content; Calabrese A performed radiological evaluation of response to treatment; and Brunetti O, Lorusso V and Silvestris N give final approval of the version to be submitted and any revised version; all the authors contributed to this manuscript.
Conflict-of-interest statement: The authors declare the absence of conflict of interests.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Nicola Silvestris, MD, Medical Oncology Unit, National Cancer Research Centre Istituto Tumori Giovanni Paolo II, Viale Orazio Flacco, 65, 70124 Bari, Italy.
n.silvestris@oncologico.bari.it
Telephone: +39-80-5555419
Received: January 26, 2016
Peer-review started: January 27, 2016
First decision: March 7, 2016
Revised: March 18, 2016
Accepted: March 30, 2016
Article in press: March 30, 2016
Published online: July 21, 2016
Processing time: 171 Days and 13.1 Hours
AIM: To identify suitable biomarkers of response to bevacizumab (BV) - it remains an open question. The measurement of serum vascular endothelial growth factor (VEGF) has been proposed as a predictive factor for this drug, even if literature data are contradictory.
METHODS: We prospectively evaluated the role of BV, total and not BV-bound VEGF and angiopoietin-2 (Ang-2) serum levels as potential predictive factors of response for BV in combination with an oxaliplatin-based chemotherapy. BV, Ang-2, total and not BV-bound VEGF levels were measured at baseline, before 2nd and 5th cycle of oxaliplatin-based chemotherapy in 20 consecutive metastatic colorectal cancer patients.
RESULTS: Results were correlated to response to treatment. Variability in BV levels have been found, with decreased level in less responding patients. In particular, the concentration of BV increased of 3.96 ± 0.69 folds in serum of responsive patients after 3 more cycles of therapy compared to those with stable or progressive disease with a 0.72 ± 0.25 and 2.10 ± 0.13 fold increase, respectively. The determination of free and total VEGF demonstrated that the ratio between the two values, evaluated immediately before the 2nd and the 5th cycle of therapy, decreased from 26.65% ± 1.33% to 15.50% ± 3.47% in responsive patients and from 53.41% ± 4.75 to 34.95% ± 2.88% in those with stable disease. Conversely, in those with progression of disease, the ratio showed the opposite behavior coming up from 25.99% ± 5.23% to 51.71% ± 5.28%. The Ang-2 levels did not show any relationship.
CONCLUSION: Our data show that the ratio of not BV-bound VEGF to total VEGF serum and BV plasma concentrations for predicting the response to BV plus oxaliplatin-based chemotherapy could be a promising biomarker of response to BV.
Core tip: In the main topic of the identification of possible reliable markers to predict response to antiangiogenic therapy, our paper represents an original contribution describing the role of not bevacizumab (BV)-bound vascular endothelial growth factor (VEGF)/total VEGF ratio and of bevacizumab serum level as predictors of response in a consecutive series of patients with metastatic colorectal cancer. In this paper the rediscovery of the predictive role of traditional biomarkers as not BV-bound VEGF/total VEGF plasma ratio together with the results of the bevacizumab pharmacokinetic in response, stable disease and progression settings of patients with metastatic colorectal cancer treated with bevacizumab plus oxaliplatin based chemotherapy supported our hypothesis.
