Recent Advances in the Treatment of Hepatocellular Carcinoma

Amit G. Singal; Jorge A. Marrero

Disclosures

Curr Opin Gastroenterol. 2010;26(3):189-195. 

In This Article

Systemic Targeted Therapy

In 2008, the first large randomized controlled trial demonstrating a significant improvement in survival with a systemic therapy was published.[41••] This trial was terminated early after finding that the median survival was improved from 7.9 months with placebo to 10.7 months with sorafenib, a multikinase inhibitor. It is important to note that the majority of the patients included in this trial had Child A cirrhosis (95%) and good performance status (92%) with advanced tumors (53% extrahepatic spread and 70% macroscopic vascular invasion). Its benefit was subsequently confirmed in an Asian-Pacific population, where there was a higher prevalence of noncirrhotic HCC due to hepatitis B.[42] This medication is well tolerated with possible serious side-effects including diarrhea, hand–foot skin reaction, hypertension, and hypophosphatemia. There are also ongoing trials to evaluate any benefit of adding sorafenib to other treatment modalities such as resection[43] or TACE.[44]

There have also been several early trials evaluating other targeted therapies for advanced HCC. Bevacizumab, an antivascular endothelial growth factor monoclonal antibody, was evaluated in 46 patients and had a median survival of 12.4 months.[45] Erlotinib, an EGFR kinase inhibitor, was tested in 38 patients with advanced HCC and showed a median survival of 13 months.[46] When used in combination, the two achieved a median progression-free survival of 9 months and a median overall survival of 15.6 months. Although these results from phase II studies are promising, they must still be confirmed in larger phase III studies.

Sorafenib is now considered standard of care for most patients with advanced HCC, but current trials have been restricted primarily to patients with Child A cirrhosis and good performance status. Systemic targeted therapy is unlikely to be tolerated or of significant benefit in patients with Child C cirrhosis or poor performance status.[47] Patients with Child B cirrhosis should be treated with caution on an individual basis until larger trials provide more data regarding safety and efficacy in these patients.

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