Prognostic significance of VEGF and HIF 1 ? in hepatocellular carcinoma patients receiving sorafenib versus metformin sorafenib combination

Abstract

Introduction: Hepatocellular carcinoma (HCC) is a major health problem. HCC burden has been increasing in Egypt in the last 10 years. Most HCC cases are diagnosed at an advanced stage with limited treatment options. Sorafenib is the standard therapy for advanced HCC, but the effectiveness is not satisfied. Metformin may decrease the possibility of HCC in diabetic patients, reduce tumor invasion and augment sensitivity to Sorafinib, however, safety and efficacy of combined treatment still unclear. As HCC is characterized by high vascularity, and vascular endothelial growth factor (VEGF) plays important role in vascularization; many studies questioned if VEGF and HIF-1 a could be predictive to sorafenib response in HCC. We conducted this study to assess the benefits from adding metformin to HCC treatment. Methods: This prospective, randomized study included 80 advanced HCC patients consecutively treated with sorafenib plus metformin (Arm A) or sorafenib alone (Arm B), prognostic value of plasma and tissue levels of VEGF and HIF 1 a were evaluated Results: We enrolled 61men and 19 women with a median age of 60 years (range 49-68 years). 57patients had Child-Pugh A while 23 had early B, the most common etiology of liver disease was hepatitis C (86%). 60% of patients were diabetic. No significant difference was detected between arm A and arm B regarding response to treatment (52.5% and 55%, p=0.5, respectively), time to disease progression (TDP; p=0.3), or OS (p=0.6. ( Low VEGF and HIF1 a plasma levels were significantly associated with better treatment response (p<0.001 for both), and higher OS (P<0.001). Patients with high expressions of VEGF & HIF had significantly poor treatment outcome (P<0.001, p=0.03; respectively), and poor OS (P<0.001 for both. ( Conclusion: No superior efficacy for adding metformin to sorafenib in advanced HCC treatment with a promising prognostic role of VEGF and HIF1 a in HCC.