Association of plasma VEGF-A, soluble VEGFR-1 and VEGFR-2 levels and clinical response and survival in advanced colorectal cancer patients receiving bevacizumab with modified FOLFOX6

For individualized bevacizumab-based therapy, non-invasive biomarkers are necessary. This study assessed the predictive value of plasma vascular endothelial growth factor (VEGF)-A, soluble VEGF receptor (sVEGFR)-1 and sVEGFR-2 levels as biomarkers for clinical response and survival in advanced colorectal cancer (CRC) patients treated with bevacizumab and modified FOLFOX6 (mFOLFOX6). Forty-six unresectable advanced CRC patients and 20 healthy controls were included in this study. CRC patients were treated with bevacizumab and mFOLFOX6. Pretreatment plasma VEGF-A, sVEGFR-1 and sVEGFR-2 levels were measured using the multiplex immunoassay. Plasma VEGF-A, sVEGFR-1 and sVEGFR-2 levels were significantly higher in CRC patients than in the healthy subjects. The plasma sVEGFR-1 levels in the responder patients [complete response (CR)/partial response (PR)] and stable disease (SD) patients were significantly lower than those in the progressive disease (PD) patients (CR/PR vs. PD, p=0.025; SD vs. PD, p=0.032), while the plasma VEGF-A and sVEGFR-2 levels did not show any significant differences between the two groups of patients. Patients with higher sVEGFR-1 levels showed a significantly poorer progression-free survival (PFS) and overall survival (OS) than those with lower VEGFR-1 levels. In contrast, VEGF-A and sVEGFR-2 did not show any significant relationship between PFS and OS according to the status of each level. In the multivariate Cox proportional hazard regression analysis, sVEGFR-1 levels showed a significant relationship between PFS and OS. These results suggest that plasma sVEGFR-1 levels have a predictive value for clinical response and survival in advanced CRC patients treated with bevacizumab and mFOLFOX6. Larger scale studies are needed to further validate our results.