Published online Jul 21, 2016. doi: 10.3748/wjg.v22.i27.6287
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.