Coagulo-fibrinolytic activity as a predictor of efficacy in bevacizumab-combined chemotherapy in metastatic colorectal cancer patients.

Abstract

533 Background: The combination of bevacizumab (BV) and chemotherapy in the first-line and second-line treatment of metastatic colorectal cancer (mCRC) has been shown to improve survival. Bevacizumab is a recombinant, humanized monoclonal antibody against vascular endothelial growth factor. However, the relationship between coagulo-fibrinolytic activity factors and treatment efficacy remains to be clarified. The aim of this study was to determine potential coagulo-fibrinolytic activity markers impacting survival. Methods: Among 119 consecutive patients included in the study, 85 received first-line FOLFOX4 plus BV 5 mg/kg and 34 received second-line FOLFIRI plus BV 5 mg/kg until progression of disease or unmanageable toxicity occurred. Coagulo-fibrinolytic activity factors, including D-dimer, thrombin antithrombin complex (TAT) and carbohydrate antigen 125 (CA125) encoded by the MUC16 mucin gene were evaluated as candidate predictors of outcome. Results: In first-line treatment, overall response, median progression-free survival (PFS) and two-year survival rate were 61.9%, 518 days and 67.3%, respectively. In second-line treatment, overall response, median PFS and median overall survival (OS) were 23.5%, 248 days and 651 days, respectively. The outcomes of the univariate analysis were as follows: normal D-dimer and CA125 levels at baseline were associated with better PFS and OS in first-line treatment; normal TAT and CA125 levels at baseline were associated with better PFS and OS in second-line treatment. According to the results of the multivariate analysis, normal D-dimer level was associated with longer PFS in first-line treatment, and only CA125 level at baseline was an independent predictor of both PFS and OS in second-line treatment. Conclusions: The results suggest that coagulo-fibrinolytic activity factors such as TAT, D-dimer or CA125 may be useful predictors of outcome in mCRC patients receiving BV in combination with chemotherapy. No significant financial relationships to disclose.