Association of prior treatment with anti-EGFR monoclonal antibodies with downregulation of circulating TRAIL and upregulation of EGFR and VEGF family ligands in metastatic colorectal cancer.

452 Background: Inhibition of growth factor receptor signaling leads to unintended compensatory pathway activation in preclinical models, which may impact the success of subsequent therapies. We hypothesized that increased circulating levels of receptor ligands after anti-EGFR monoclonal antibody (mAb) therapy, including VEGF ligands or EGFR family ligands, may provide insights into clinically relevant feedback mechanisms. Methods: Plasma was obtained from 96 metastatic colorectal cancer (mCRC) patients: 48 previously treated with anti-EGFR mAbs and 48 mCRC patients previously treated without prior anti-EGFR therapy who were matched for total months of prior chemotherapy and interval since last chemotherapy treatment. Plasma levels of circulating cytokines with emphasis on EGFR and VEGF ligands were determined using suspension bead multiplex assay (BioRad). Comparisons were done by the two-sided nonparametric Wilcoxon signed rank test. Multivariate linear regression analysis was done with forward selectio...