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Vol 5, No 6 (2009)
Review paper
Published online: 2010-03-01
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Targeted therapy of hepatocellular carcinoma with sorafenib. Finally a breakthrough or maybe just the beginning of a long way?

Piotr Potemski
Onkol. Prak. Klin 2009;5(6):229-236.

open access

Vol 5, No 6 (2009)
REVIEW ARTICLES
Published online: 2010-03-01

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.

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.
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Keywords

hepatocellular carcinoma; sorafenib; overall survival; quality of life; predictive factors

About this article
Title

Targeted therapy of hepatocellular carcinoma with sorafenib. Finally a breakthrough or maybe just the beginning of a long way?

Journal

Oncology in Clinical Practice

Issue

Vol 5, No 6 (2009)

Article type

Review paper

Pages

229-236

Published online

2010-03-01

Bibliographic record

Onkol. Prak. Klin 2009;5(6):229-236.

Keywords

hepatocellular carcinoma
sorafenib
overall survival
quality of life
predictive factors

Authors

Piotr Potemski

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