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, α-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.