High Circulating Endothelial Progenitor Levels Associated with Poor Survival of Advanced Hepatocellular Carcinoma Patients Receiving Sorafenib Combined with Metronomic Chemotherapy

Objectives: We examined whether circulating endothelial progenitor (CEP) and circulating endothelial cell (CEC) levels had associations with the survival of patients who received antiangiogenic therapy for advanced hepatocellular carcinoma (HCC). Methods: Patients with advanced HCC were enrolled into a phase II trial evaluating a combination of sorafenib and metronomic chemotherapy with tegafur/uracil as first-line systemic therapy. CEPs and CECs were enumerated with six-color flow cytometry at baseline, 2 weeks, and 4 weeks after treatment and analyzed for their associations with treatment outcomes along with other clinicopathologic factors. Results: Forty patients were enrolled. Baseline CEP and CEC levels were not associated with tumor stages, alpha-fetoprotein levels, or macrovascular invasion. By univariate analysis, a high baseline CEP level was a significant predictor of poor progression-free survival (PFS) and overall survival (OS) (p = 0.02 and p = 0.004, respectively). The high baseline CEP level remained an independent, significant predictor of poor PFS [hazard ratio (HR) 1.953, p = 0.049] and OS (HR 2.512, p = 0.004) in multivariate analysis. On the other hand, the baseline or posttreatment CEC levels were not associated with PFS or OS. Conclusion: High baseline CEP levels were associated with poor survival in patients with advanced HCC receiving sorafenib-based antiangiogenic combination therapy. Copyright (C) 2011 S. Karger AG, Basel