Total and not bevacizumab-bound vascular endothelial growth factor as potential predictive factors to bevacizumab-based chemotherapy in colorectal cancer

总血管内皮生长因子和非贝伐单抗结合血管内皮生长因子是结直肠癌贝伐单抗化疗的潜在预测因素

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作者: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

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.

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.

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 2(nd) and 5(th) 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 2(nd) and the 5(th) 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.

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