Clinical Trials of Combined Molecular Targeted Therapy and Locoregional Therapy in Hepatocellular Carcinoma: Past, Present, and Future

Abstract

Background: Sorafenib, a multikinase inhibitor that targets angiogenesis in hepatocellular carcinoma (HCC), has become a standard treatment for advanced-stage HCC and has shown survival benefits in recent clinical trials. Transarterial chemoembolization (TACE) and sorafenib are currently standard treatments for intermediate and advanced-stage HCC, respectively. Combined locoregional therapy, including TACE and molecular targeted therapies such as sorafenib, is an issue under active investigation in an attempt to improve the outcomes of patients with unresectable HCC. Summary: Various clinical trials of these combined strategies have been conducted; however, the designs of these studies are diverse in terms of treatment modalities and schedules; comparisons with controls, baseline tumor stages, and hepatic functional reserves; and outcome measures. Key Messages: This article reviews heterogeneity in the design of recent clinical trials of combined locoregional and molecular targeted therapies and briefly addresses future study directions.

Current management of hepatocellular carcinoma: An Eastern perspective

“…Overall survival times were 8.4 and 8.2 mo for sorafenib and other treatments, respectively, and the difference was not significant [82,83] . To improve the efficacy of sorafenib, combination therapy or a multidisciplinary approach may be needed [84] . Several newer molecular target therapeutic agents were evaluated in clinical trials.…”

Sorafenib after Arterial Chemoembolization in Child-Pugh A and B Cirrhotic Patients with Intermediate Hepatocellular Carcinoma: A Retrospective Analysis

“…Other studies have already shown a similar increase in the survival rate of patients treated with sorafenib after TACE, hypothesizing that the prolonged survival would be achieved in these patients because sorafenib can control VEGF levels, which increase after TACE [12].…”

“…One of the first randomized studies showed a longer time for the disease progression in patients with intermediate tumor stage [9]. Many other studies have been conducted worldwide, but when they are critically analyzed the authors have no doubts that more studies are needed to provide more reliable data about the indications of treatment combining TACE and sorafenib [10]- [12].…”

Targeting of growth factors in the treatment of hepatocellular carcinoma: The potentials of polysaccharides

“…Chitosan is a natural polysaccharide composed of randomly distributed β- [1][2][3][4]-linked D-glucosamine and N-acetyl-D-glucosamine. Low molecular weight chitosan (LMWC) can be used as a carrier for RNAi drugs directed against VEGF (106).…”

“…HCC represents the most common histological type of liver cancer, accounting for 70-85% of cases (2). Its treatment may include local ablation, surgical resection, trans-catheter arterial chemoembolization and the administration of chemotherapeutic agents (3,4). However, at the time of their diagnosis, HCC tumors may be too large or may have expanded into nearby major blood vessels or metastasized, rendering the majority of HCC patients unsuitable for treatment by surgical resection (5).…”