Prognostic values of baseline circulating endothelial progenitor level for advanced hepatocellular carcinoma (HCC) patients under antiangiogenic therapy.

Abstract

4063 Background: Antiangiogenic therapy, including sorafenib and metronomic chemotherapy, is effective in the treatment of advanced HCC. Circulating endothelial progenitor cells (CEPs) and circulating endothelial cells (CECs) are potential surrogate markers for angiogenic activity. The study evaluated their significance as prognostic or predictive markers in advanced HCC patients (pts) under anti-angiogenic therapy. Methods: Advanced HCC pts, enrolled in a phase II study (Shen et al: ASCO annual meeting 2009: Abs 4589) and its extended cohort, were treated with sorafenib plus metronomic oral tegafur/uracil until disease progression. Tumor response was performed every two months following RECIST criteria. CEPs and CECs were enumerated before treatment, 2 weeks and 4 weeks after start of therapy by six-color flow-cytometry. CD31+/CD45-/CD146+/CD133- cells were defined as CECs, and CD31+/CD45-/CD146+/CD133+ cells as CEPs. 7-AAD staining was used to differentiate viable and apoptotic cells. Results: 68 pts have been treated with sorafenib plus metronomic tegafur/uracil. The best tumor response were 4 PR (6%) and 35 SD (52%); the median PFS and OS were 3.7 (95% CI, 2.4-5.0) and 7.2 months (95% CI, 2.5-11.8), respectively. 40 pts consented to participate in the biomarker study. Of them, there were 1 (3%) PR and 20 (50%) SD; the median PFS and OS were 3.2 (95% CI, 0.6-5.8) and 5.6 (95% CI, 2.2-8.9) months, respectively. No significant associations between baseline CEP/CEC levels and patient characteristics were found. Baseline CEP/CEC levels did not predict disease control rate (CR+PR+SD). By univariate analysis, however, higher baseline CEP level was a significant predictor for poorer PFS and OS. Higher baseline CEP level remained an independent significant predictor for poor PFS (HR 1.953, p = 0.049) and OS (HR 3.077, p = 0.002) in multivariate analysis. Conclusions: Higher baseline CEP level predicts poorer PFS and OS for advanced HCC pts under anti-angiogenic therapy. This finding mandates further validation in large studies. This study was supported by the grant of NSC 98-3112-B-002-038. No significant financial relationships to disclose.