title: Total and not bevacizumab-bound vascular endothelial growth factor as potential predictive factors to bevacizumab-based chemotherapy in colorectal cancer.
abstract: OBJECTIVE
  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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Amalia
authors.initials: A
authors.lastname: Azzariti
authors.affiliation: 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.
authors.forename: Letizia
authors.initials: L
authors.lastname: Porcelli
authors.affiliation: 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.
authors.forename: Oronzo
authors.initials: O
authors.lastname: Brunetti
authors.affiliation: 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.
authors.forename: Marzia
authors.initials: M
authors.lastname: Del Re
authors.affiliation: 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.
authors.forename: Vito
authors.initials: V
authors.lastname: Longo
authors.affiliation: 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.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Nardulli
authors.affiliation: 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.
authors.forename: Michele
authors.initials: M
authors.lastname: Signorile
authors.affiliation: 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.
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Angela
authors.initials: A
authors.lastname: Calabrese
authors.affiliation: 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.
authors.forename: Anna Elisa
authors.initials: AE
authors.lastname: Quatrale
authors.affiliation: 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.
authors.forename: Evaristo
authors.initials: E
authors.lastname: Maiello
authors.affiliation: 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.
authors.forename: Vito
authors.initials: V
authors.lastname: Lorusso
authors.affiliation: 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.
authors.forename: Nicola
authors.initials: N
authors.lastname: Silvestris
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000097:blood* / Q000627:therapeutic use; D042702:Angiopoietin-2 / Q000097:blood*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab / Q000097:blood* / Q000627:therapeutic use; D000069287:Capecitabine / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D000077150:Oxaliplatin; D011379:Prognosis; D011446:Prospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D020533:Angiogenesis Inhibitors; D042702:Angiopoietin-2; D009944:Organoplatinum Compounds; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil
keywords: Angiopoietin 2; Bevacizumab; Biomarker; Metastatic colorectal cancer; Predictive factor; Vascular endothelial growth factor