Vascular normalization therapy with targeted localized vessel bevacizumab infusion in hepatocellular carcinoma after transarterial chemoembolization failure

Abstract

Background: Hepatocellular carcinoma (HCC) is a highly vascularized tumor in which abnormal blood vessels contribute to poor treatment efficacy and prognosis. In this study, we assessed the efficacy, safety, and potential ability of bevacizumab to normalize tumor vascularity in patients with advanced HCC. Methods: Patients with histologically or clinically confirmed advanced HCC that were refractory to conventional transarterial chemoembolization (c-TACE) received a transarterial infusion of bevacizumab (5 mg/kg), followed by c-TACE (named as BEVA-TACE). The primary endpoint was overall survival (OS), which was defined as the time from a patient identified as TACE refractory to the occurrence of death. The secondary endpoints included progression-free survival (PFS) and the disease control rate (DCR). Results: From January 2014 to December 2017, 20 patients with Barcelona Clinic Liver Cancer (BCLC) staging scores C (80.0%) or D (20.0%) received BEVA-TACE. The median OS time was 9.2 months [95% confidence interval (CI): 2.1–22.6 months]. The median PFS time was 6.3 months (95% CI: 1.0–10.5 months). Despite the late stage, 1 patient (5.0%) had a complete response (CR), 6 patients (30.0%) had a partial response (PR), and 10 patients (50.0%) had stable disease (SD) [overall response rate (ORR) 30.0%; DCR 85.0%]. The most common adverse events (AEs) were postembolic syndrome (25%), hyperbilirubinemia (10.0%), and melena (10.0%). Severe III–IV oral mucositis and hypertension were observed in only 1 patient (5.0%) during the follow-up period. Conclusions: BEVA-TACE showed clinical efficacy, and patients with TACE-refractory HCC had acceptable AE rates. A low dose of targeted localized vessel bevacizumab infusion may normalize the condition of tumor blood vessels in patients with advanced HCC.