Systemic therapy of hepatocellular carcinoma: are we making progress?

Adv Ther. 2008 Nov;25(11):1089-104. doi: 10.1007/s12325-008-0113-z.


Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer deaths. Surgical resection, with or without transplantation, can result in long-term survival. However, surgery can only be performed in about 15% of patients with HCC and the 5-year survival rate is only approximately 33%-50% after potentially curative resection. Percutaneous ethanol injection, radiofrequency ablation, and transarterial chemoembolization are invasive techniques that have shown efficacy in reducing tumor bulk. Similarly, systemic chemotherapy may induce tumor responses, but a survival benefit has not been clearly demonstrated. In addition, the lack of efficacy of antiandrogens, tamoxifen, and single-agent interferon has now been confirmed.Sorafenib is a multikinase inhibitor with antiangiogenic, proapoptotic, and Raf kinase inhibitory activity. In a large, multicenter, randomized, phase 3 trial there was a significant improvement in both time to disease progression and overall survival with sorafenib compared with placebo. Sorafenib is the first agent to demonstrate a consistent improvement in overall survival for patients with advanced HCC. Further studies are required to determine the role of other molecular-targeted therapies, either alone or in combination with sorafenib in patients with advanced HCC. Further studies are also required to determine the role of sorafenib in combination with locoregional therapies (eg, transarterial chemoembolization), and the role of sorafenib as adjuvant therapy following surgery.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Benzenesulfonates / therapeutic use
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / surgery
  • Carcinoma, Hepatocellular / therapy*
  • Catheter Ablation
  • Chemoembolization, Therapeutic
  • Estrogens / therapeutic use
  • Humans
  • Injections, Intravenous
  • Interferons / therapeutic use
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / surgery*
  • Niacinamide / analogs & derivatives
  • Palliative Care
  • Phenylurea Compounds
  • Pyridines / therapeutic use
  • Risk Factors
  • Sorafenib
  • Tretinoin / analogs & derivatives
  • Tretinoin / therapeutic use


  • Antineoplastic Agents
  • Benzenesulfonates
  • Estrogens
  • Phenylurea Compounds
  • Pyridines
  • Niacinamide
  • Tretinoin
  • 3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid
  • Interferons
  • Sorafenib