Chemotherapy for advanced hepatocellular carcinoma in the sorafenib age.
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.
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.
Koji
K
Miyahara
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
K
Nouso
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.
Kazuhide
K
Yamamoto
D000465:Algorithms; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D018450:Disease Progression; D006499:Hepatic Artery / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008495:Medical Oncology / Q000639:trends; D058990:Molecular Targeted Therapy / Q000379:methods; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D000077157:Sorafenib; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
Biomarker; Clinical trial; Hepatic arterial infusion chemotherapy; Hepatocellular carcinoma; Molecular targeted therapy; Sorafenib