Targeted Therapy for Liver Cancer: Updated Review in 2012

Masatoshi      Kudo

Abstract

May 2007, sorafenib (Nexavar®) was approved for “unresectable hepatocellular carcinoma (HCC)”, and was the first molecular targeted agent for use in HCC. To date, sorafenib is the only molecular-targeted agent, whose survival benefit has been demonstrated in two global phase III randomized controlled trials, and has now been approved worldwide. Phase III clinical trials of other molecular targeted agents comparing them with sorafenib as first-line treatment agents are now ongoing. Phase III clinical trials of several targeted agents comparing them with placebo as second-line treatment agents for patients who failed or was intolerable to sorafenib are also ongoing. In addition, combination of sorafenib with standard treatment such as resection, ablation, transarterial chemoembolization, and hepatic arterial infusion chemotherapy are ongoing.This review outlines the clinical utility of sorafenib in the treatment algorithm of HCC. Furthermore, it also reviews the current status of clinical trials of new agents or combination therapy with sorafenib and standard treatment. Finally, further prospect of the paradigm shift of the HCC treatment is also discussed.

Keywords: Brivanib, complete remission, everolimus, hepatocellular carcinoma, molecular targeted agent, sorafenib, acidic fibroblast growth factor, alpha-fetoprotein, alanine transaminase, aspartate transaminase, basic fibroblast growth factor, best supportive care, complete response, des-gamma-carboxyprothrombin, dose-limiting toxicities, epidermal growth factor, epidermal growth factor receptor, fibroblast growth factor