Hemorrhagic events in hepatocellular carcinoma patients treated with antiangiogenic therapies.

The presence of cirrhosis increases the potential risk of hemorrhage for patients with hepatocellular carcinoma (HCC). We evaluated the relative risk for hemorrhage in patients with HCC treated with antiangiogenic agents. We performed a systematic review and meta-analysis of antiangiogenic studies in HCC from 1995 to 2011. For nonrandomized studies we compared bleeding risk with other HCC single-arm studies that did not include an antiangiogenic agent. To separate disease-specific factors we also performed a comparison analysis with renal cell cancer (RCC)) studies that evaluated sorafenib. Sorafenib was associated with increased bleeding risk compared to control for all grade bleeding events (odds ratio [OR] 1.77; 95% confidence interval [CI] 1.04, 3.0) but not grade 3-5 events in both HCC and RCC (OR 1.46; 95% CI 0.9, 2.36; P=0.45). When comparing the risk of bleeding in single-arm phase 2 studies evaluating antiangiogenic agents, this risk for all events (OR 4.34; 95% CI 2.16, 8.73) was increased compared to control.