SDF-1 and VEGF-C as potential circulating angiogenic biomarkers for bevacizumab in patients with metastatic colorectal cancer.

Abstract

480 Background: Bevacizumab (BV) plus chemotherapy (chemo) has been shown to improve survival for metastatic colorectal cancer (mCRC). Stromal cell-derived factor-1 (SDF-1) is known as a ligand for CXCR-4. We previously reported that proportion of CXCR4-positive circulating endothelial cells at baseline was correlated with the prognosis of BV plus chemo (Matsusaka, et al. Cancer. 2011). The aim of this study was to investigate changes during treatment in serum candidate cytokines including SDF-1 as potential markers of treatment response to BV. Methods: Patients receiving first-line BV plus chemo with mCRC were enrolled in this prospective study. Serum samples were analyzed before initiation of treatment and during treatment (on days 14 and 56) and at the time of progressive disease. Correlation between tumor response and changes in serum levels of the cytokines (such as VEGF, SDF-1, Ang-1 and -2, etc.) were investigated. Differences in the means of continuous measurements were tested by the Student’s t test. A two-way repeated-measures analysis of variance was used to evaluate differences between sequential continuous variables. Results: 24 were enrolled at the first interim analysis. 14 patients were assessable; some who got conversion surgery or discontinued treatment due to toxicity in early were excluded. Tumor response was achieved in 57% of the patients. SDF-1 levels at baseline (p=0.045) and on days 14 (p=0.049) were significantly lower in tumor responder, while a trend toward higher on days 56 compared to non-responder. The results of a two-way repeated-measures analysis of variance to evaluate differences between sequential continuous variables showed significant differences in VEGF-C (p=0.043) and SDF-1 (p=0.02), influenced by tumor response. Serum levels of SDF-1 trended toward increase on days 14 and decrease on days 56, whilst VEGF-C trended toward decrease on days 14 and 56. Conclusions: Changes Serum levels of SDF-1 and VEGF-C showed correlation with tumor response to BV plus chemo, suggesting that these surrogate markers may represent anti-angiogenic condition for BV treatment. This study is currently ongoing, and further analysis will be performed in more population.