Journal
CANCERS
Volume 12, Issue 10, Pages -Publisher
MDPI
DOI: 10.3390/cancers12102961
Keywords
hepatocellular carcinoma; sorafenib; vascular complications; thromboembolic events; bleeding complications; metabolic risk factors; cardiovascular risk
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Simple Summary Inhibition of vascular endothelial growth factor receptor (VEGFR) signaling is associated with an increased risk of thromboembolic and bleeding complications in cancer patients and may cause fatal side effects. The multityrosine kinase inhibitor sorafenib represents an important treatment option for patients with hepatocellular carcinoma (HCC), as all currently approved second-line treatments have only been approved in sorafenib-experienced patients. However, safety concerns regarding sorafenib treatment in patients with cardiovascular disease have been raised. Therefore, we retrospectively analyzed the incidence of arterial/venous thromboembolic and bleeding complications in 252 patients with HCC treated with sorafenib. Importantly, the incidence of arterial/venous thromboembolic events was low even though more than half of patients had advanced liver dysfunction and a substantial cardiovascular risk according to Framingham risk score. Bleeding complications occurred in every fifth patient. In conclusion, sorafenib represents a safe treatment option even in patients with an increased cardiovascular risk. VEGF(R)-targeted therapies are associated with an increased risk of thromboembolism and bleeding, which might be pronounced in patients with increased cardiovascular risk. Nevertheless, sorafenib represents an important treatment option in patients with hepatocellular carcinoma (HCC). We retrospectively investigated the risk of arterial/venous thromboembolic and bleeding events in 252 patients treated with sorafenib for HCC between 05/2006 and 03/2020 at the Medical University of Vienna. Cardiovascular risk was assessed using Framingham score. Eight patients (3.2%) experienced 11 arterial/venous thromboembolic events. Only two patients (0.8%) developed arterial thromboembolism even though cardiovascular risk was low, intermediate, and high in 15 (8.7%), 104 (60%), and 54 (31.2%) of 173 assessable patients. Median overall survival (OS) was shorter in the high risk vs. low/intermediate risk group 7.4 (95% CI: 3.4-11.3) vs. 10.0 (95% CI: 6.8-13.2 months) and independently associated with OS in multivariable analysis HR: 1.53 (95% CI: 1.07-2.19; p = 0.019). Forty-eight (19%) patients experienced a bleeding, most commonly gastrointestinal bleeding (14%) followed by epistaxis (4.7%). Advanced liver dysfunction was not associated with an increased incidence of bleeding/venous thromboembolism. Sorafenib represents a safe treatment option even in patients with increased cardiovascular risk. Bleeding complications were comparable with previous reports, even though patients with more advanced liver disease were included.
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