The Korean Journal of Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma |
Jeong Heo |
Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea |
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ABSTRACT |
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Background Most cases of hepatocellular carcinoma
occur in the Asia-Pacific region, where
chronic hepatitis B infection is an important aetiological
factor. Assessing the efficacy and safety of
new therapeutic options in an Asia-Pacific population
is thus important. We did a multinational
phase III, randomised, double-blind, placebocontrolled
trial to assess the efficacy and safety of
sorafenib in patients from the Asia-Pacific region
with advanced (unresectable or metastatic) hepatocellular
carcinoma. Methods: Between Sept 20,
2005, and Jan 31, 2007, patients with hepatocellular
carcinoma who had not received previous systemic
therapy and had Child-Pugh liver function class A,
were randomly assigned to receive either oral
sorafenib (400 mg) or placebo twice daily in 6-week
cycles, with efficacy measured at the end of each
6-week period. Eligible patients were stratified by
the presence or absence of macroscopic vascular
invasion or extrahepatic spread (or both), Eastern
Cooperative Oncology Group performance status, and
geographical region. Randomisation was done centrally
and in a 2:1 ratio by means of an interactive
voice-response system. There was no predefined
primary endpoint; overall survival, time to progression
(TTP), time to symptomatic progression
(TTSP), disease control rate (DCR), and safety were
assessed. Efficacy analyses were done by intention
to treat. This trial is registered with Clinical-
Trials.gov, number NCT00492752.
Findings: 271 patients from 23 centers in China,
South Korea, and Taiwan were enrolled in the study.
Of these, 226 patients were randomly assigned to the
experimental group (n=150) or to the placebo group
(n=76). Median overall survival was 6.5 months
(95% CI 5.56-7.56) in patients treated with sorafenib,
compared with 4.2 months (3.75-5.46) in those
who received placebo (hazard ratio [HR] 0.68 [95%
CI 0.50-0.93]; P=0.014). Median TTP was 2.8 months
(2.63-3.58) in the sorafenib group compared with 1.4
months (1.35-1.55) in the placebo group (HR 0.57
[0.42-0.79]; P=0.0005). The most frequently reported
grade 3/4 drug-related adverse events in the 149
assessable patients treated with sorafenib were
hand-foot skin reaction (HFSR; 16 patients [10.7%]),
diarrhoea (nine patients [6.0%]), and fatigue (five
patients [3.4%]). The most common adverse events
resulting in dose reductions were HFSR (17 patients
[11.4%]) and diarrhoea (11 patients [7.4%]); these
adverse events rarely led to discontinuation. Interpretation:
Sorafenib is effective for the treatment of
advanced hepatocellular carcinoma in patients from
the Asia-Pacific region, and is well tolerated. Taken
together with data from the Sorafenib Hepatocellular
Carcinoma Assessment Randomised Protocol (SHARP)
trial, sorafenib seems to be an appropriate option for
the treatment of advanced hepatocellular carcinoma. |
KeyWords:
Carcinoma, Hepatocellular; Tyrosine kinase inhibitor; Sorafenib |
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