Development of systemic therapy for hepatocellular carcinoma at 2013: updates and insights.
A growing number of multi-targeted tyrosine kinase inhibitor (TKI) has undergone testing for hepatocellular carcinoma (HCC). Unfortunately, this enthusiasm has recently been discouraged by a number of negative phase III studies on several anti-angiogenic TKIs in HCC. Several postulations have been made to account for this phenomenon, namely the plateau effects of anti-angiogenesis approach, the heterogeneity of HCC in terms of background hepatitis/cirrhosis and tumor biology, as well as the way how clinical trials are designed. Regardless of the underlying reasons, these results suggested that alternative strategies are necessary to further develop systemic therapy for HCC. Several new strategies are currently evaluated: for examples, molecular agents with activities against targets other than vascular endothelial growth factor receptor are being evaluated in on-going clinical trials. In addition, different approaches of targeted agents in combination with various treatment modalities, such as concurrently with another molecular agent, cytotoxic chemotherapy or transarterial chemoembolization, are being developed. This review aims to give a summary on the results of recently released clinical trials on TKIs, followed by discussion on some of the potential novel agents and combinational approaches. Future directions for testing innovative systemic agents for HCC will also be discussed.
Stephen L Chan, Winnie Yeo, Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
Stephen L
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Chan
Stephen L Chan, Winnie Yeo, Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
Winnie
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Yeo
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001120:Arginine / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D002986:Clinical Trials as Topic; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008113:Liver Neoplasms / Q000628:therapy*; D008495:Medical Oncology / Q000639:trends*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D001120:Arginine; C546842:MTOR protein, human; D019859:Proto-Oncogene Proteins c-met; D040301:Vascular Endothelial Growth Factor Receptor-2; D058570:TOR Serine-Threonine Kinases
Biologics; Clinical trial; Liver neoplasms; Staging; Systemic treatment