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World J Gastroenterol. Apr 21, 2014; 20(15): 4151-4159
Published online Apr 21, 2014. doi: 10.3748/wjg.v20.i15.4151
Chemotherapy for advanced hepatocellular carcinoma in the sorafenib age
Koji Miyahara, Kazuhiro Nouso, Kazuhide Yamamoto
Koji Miyahara, Kazuhiro Nouso, Kazuhide Yamamoto, Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama-city, Okayama 700-8558, Japan
Kazuhiro Nouso, Department of Molecular Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama-city, Okayama 700-8558, Japan
Author contributions: Miyahara K and Nouso K wrote the paper; Yamamoto K critically revised the manuscript for important intellectual content.
Correspondence to: Koji Miyahara, MD, PhD, Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama-city, Okayama 700-8558, Japan. mkojisup@yahoo.co.jp
Telephone: +81-86-235-7219 Fax: +81-86-225-5991
Received: September 4, 2013
Revised: January 2, 2014
Accepted: February 26, 2014
Published online: April 21, 2014
Processing time: 225 Days and 4.7 Hours
Abstract

The kinase inhibitor sorafenib is the only systemic therapy proven to have a positive effect on survival of patients with advanced hepatocellular carcinoma (HCC). After development of sorafenib and its introduction as a therapeutic agent used in the clinic, several critical questions have been raised. Clinical parameters and biomarkers predicting sorafenib efficacy are the most important issues that need to be elucidated. Although it is difficult to know the responders in advance using conventional characteristics of patients, there are specific serum cytokines and/or gene amplification in tumor tissues that have been reported to predict efficacy of sorafenib. Risk and benefits of continuation of sorafenib beyond radiological progression is another issue to consider because no other standard therapy for advanced HCC as yet exists. In addition, effectiveness of the expanded application of sorafenib is still controversial, although a few studies have shed some light on combinational treatment with sorafenib for intermediate-stage HCC. Recently, over 50 relevant drugs have been developed and are currently under investigation. The efficacy of some of these drugs has been extensively examined, but none have demonstrated any superiority over sorafenib, so far. However, there are several drugs that have shown efficacy for treatment after sorafenib failure, and these are proceeding to further studies. To address these issues and questions, we have done extensive literature review and summarize the most current status of therapeutic application of sorafenib.

Keywords: Biomarker; Molecular targeted therapy; Clinical trial; Hepatic arterial infusion chemotherapy; Hepatocellular carcinoma; Sorafenib

Core tip: Sorafenib is the only systemic therapy proven to have a positive effect on survival and to be well tolerated in patients with advanced hepatocellular carcinoma (HCC). We summarize the most current status of sorafenib therapy, focusing on (1) safety and efficacy of sorafenib for advanced HCC; (2) biomarkers predicting efficacy of sorafenib; (3) expanded application for the treatment of non-advanced HCC; (4) sorafenib efficacy beyond radiological progression; and (5) novel therapeutics and hepatic arterial infusion chemotherapy.