Vol 5, No 6 (2009)
Review paper
Published online: 2010-03-01
Targeted therapy of hepatocellular carcinoma with sorafenib. Finally a breakthrough or maybe just the beginning of a long way?
Onkol. Prak. Klin 2009;5(6):229-236.
Abstract
Hepatocellular carcinoma (HCC) accounts for more than 5% of all cancers and it is the third cause of cancerrelated
deaths worldwide. The main risk factors of HCC include: cirrhosis related to infections caused by
hepatitis B or C virus and to alcohol abuse, and exposure to aflatoxins. Prognosis is poor and a 5-year
survival rate in Europe is 9%. Systemic chemotherapy in inoperable HCC has no proven impact on patient
survival. In recent years due to advances in knowledge of the molecular biology of HCC a targeted therapy
with sorafenib has been introduced. Sorafenib is a multikinase inhibitor that inhibits surface receptors (VEGFR
1-3, PDGFR-β) and intracellular Raf kinases. Two randomized phase III trials, SHARP and the Asia-Pacific region trial consistently showed that patients treated with first-line sorafenib have longer survival in comparison
with placebo. However, both failed to show any improvement in the time to symptomatic progression
which was defined as a significant deterioration in quality of life, or a decrease in ECOG performance status
to 4, or death. Moreover, no clear clinical predictive factors were identified. However, patients with extrahepatic
spread seemed to benefit from sorafenib to far less extent in comparison with patients with disease
confined to liver. A doctor should discuss with her/his patient these issues thoroughly prior to start of sorafenib
therapy. Only patients with Child-Pugh class A liver function and ECOG 0–1 performance status should
be considered for such treatment. The discovery of molecular predictive factors is eagerly awaited.
Keywords: hepatocellular carcinomasorafeniboverall survivalquality of lifepredictive factors
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