title: Association between baseline VEGF/sVEGFR-2 and VEGF/TSP-1 ratios and response to metronomic chemotherapy using cyclophosphamide and celecoxib in patients with advanced breast cancer.
abstract: BACKGROUND
  Metronomic chemotherapy (MCT) with cyclophosphamide (Cy) and celecoxib (Cel) has therapeutic efficacy and low toxicity profile in advanced breast cancer patients (ABCP), but no reliable biomarkers of response have been found yet that allow patient selection for treatment.
  
  
  OBJECTIVE
  To investigate the potential role as biomarkers of pro- and antiangiogenic parameters and evaluate their response in ABCP receiving metronomic Cy 50 mg p.o./day + Cel 400 mg p.o./day.
  
  
  METHODS
  Serum levels of vascular endothelial growth factor-C (VEGF-C), soluble VEGF receptors 2 and 3 (sVEGFR-2, sVEGFR-3), were measured at different time points in 13/15 patients included in a phase II trial of MCT with Cy+Cel.
  
  
  RESULTS
  Serum levels of sVEGFR-2 and sVEGFR-3 increased significantly during treatment (P = 0.0392; P = 0.0066, respectively). VEGF-C showed no significant modifications. Previous determinations of VEGF and TSP-1 in the same patients were utilized. VEGF/sVEGFR-2, VEGF/TSP-1, and VEGF-C/sVEGFR-3 ratios decreased significantly along the treatment (P = 0.0092; P = 0.0072; P = 0.0141, respectively). Nonsignificant variations were observed for VEGF-C/sVEGFR-2 ratio. Baseline values of VEGF/sVEGFR-2 and VEGF/TSP-1 ratios were associated with time to progression (TTP) (P = 0.0407; P = 0.0394, respectively) meanwhile baseline VEGF was marginally significant (P = 0.0716). Patients with values lower than the 50th percentile for both ratios showed longer TTP.
  
  
  CONCLUSIONS
  We have identified the baseline VEGF/sVEGFR-2 and VEGF/TSP-1 ratios as potential biomarkers of response in ABCP treated metronomically with Cy+Cel. This finding warrants its confirmation in a higher number of patients.
authors: Institute of Experimental Genetics, School of Medical Sciences, National University of Rosario, Rosario, Argentina.
authors: H A
authors: HA
authors: Perroud
authors: M J
authors: MJ
authors: Rico
authors: C M
authors: CM
authors: Alasino
authors: S M
authors: SM
authors: Pezzotto
authors: V R
authors: VR
authors: Rozados
authors: O G
authors: OG
authors: Scharovsky
mesh_terms: D059250:Administration, Metronomic; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D000068579:Celecoxib; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D013449:Sulfonamides / Q000008:administration & dosage; D019700:Thrombospondin 1 / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D011720:Pyrazoles; D013449:Sulfonamides; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D003520:Cyclophosphamide; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3; D000068579:Celecoxib