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

• Published in: World journal of gastroenterology : WJG Vol. 22; no. 27; pp. 6287 - 6295
• Main Authors: Azzariti, Amalia, Porcelli, Letizia, Brunetti, Oronzo, Del Re, Marzia, Longo, Vito, Nardulli, Patrizia, Signorile, Michele, Xu, Jian-Ming, Calabrese, Angela, Quatrale, Anna Elisa, Maiello, Evaristo, Lorusso, Vito, Silvestris, Nicola
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 21-07-2016
• Subjects: 2;Metastatic; Adult; Aged; Angiogenesis Inhibitors - blood; Angiogenesis Inhibitors - therapeutic use; Angiopoietin-2 - blood; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab - blood; Bevacizumab - therapeutic use; Bevacizumab;Vascular; cancer;Biomarker; Capecitabine - administration & dosage; colorectal; Colorectal Neoplasms - blood; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; endothelial; factor;Angiopoietin; Female; Fluorouracil - therapeutic use; growth; Humans; Leucovorin - therapeutic use; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds - administration & dosage; Organoplatinum Compounds - therapeutic use; Prognosis; Prospective Studies; Prospective Study; Vascular Endothelial Growth Factor A - blood; Biomarker; Angiopoietin 2; Predictive factor; Vascular endothelial growth factor; Metastatic colorectal cancer; Bevacizumab
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v22.i27.6287

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 oxaliplatinbased chemotherapy. BV, Ang-2, total and not BVbound 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.