Source

Gastrointestinal Malignancy Section, Medical Oncology Branch, National Cancer Institute.

Abstract

BACKGROUND:

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 anti-angiogenic agents.

PATIENTS AND METHODS:

We performed a systematic review and meta-analysis of anti-angiogenic studies in HCC from 1995 to 2011. For non-randomized studies we compared bleeding risk with other HCC single-arm studies which did not include an anti-angiogenic agent. To separate disease-specific factors we also performed a comparison analysis with renal cancer studies which evaluated sorafenib.

RESULTS:

Sorafenib was associated with increased bleeding risk compared to control for all grade bleeding events (OR 1.77; 95% CI 1.04, 3.0) but not grade 3-5 events in both HCC and RCC ((OR1.46 95% CI 0.9, 2.36 [p=0.45]). When comparing the risk of bleeding in single-arm phase 2 studies evaluating anti-angiogenic agents, this risk for all events (OR 4.34; 95% CI 2.16, 8.73) was increased compared to control.

CONCLUSIONS:

This analysis of both randomized and non-randomized studies evaluating an anti-angiogenic agent in HCC showed that whilst the use of sorafenib was associated with an increased risk of bleeding in HCC, this was primarily for lower grade events and similar in magnitude to the risk encountered in RCC.