الفهرس 
MOLECULAR BIOLOGY OF HCC
Bile Duct CarcinomaOnly 14 pages are availabe for public view
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Abstract
Hepatocellular carcinoma (HCC) is the fifth most
common cancer worldwide and the third most common cause
of cancer mortality, with an estimated worldwide prevalence of
632,000 cases. Accounting for about 90% of all primary liver
cancers, HCC is unique in that it develops in the background of
well-recognized risk factors that are responsible for marked
variations of the tumor prevalence and clinical presentation
worldwide.
The burden of hepatocellular carcinoma (HCC) has been
increasing in Egypt with a doubling in the incidence rate in the
past 10 years. This has been attributed to several biological
(e.g. hepatitis B and C virus infection) and environmental
factors (e.g. aflatoxin, AF). Other factors such as cigarette
smoking, occupational exposure to chemicals such as
pesticides, and endemic infections in the community, such as
schistosomiasis, may have additional roles in the etiology or
progression of the disease.
The only approved systemic therapy for patients with
advanced hepatocellular carcinoma (HCC) till now is
sorafenib. a preliminary study suggested that capecitabine, an
oral fluoropyrimidine may be effective in advanced HCC. We
have testified this hypothesis in this phase 2 study.The study population consisted of patients with
advanced-stage hepatocellular carcinoma, as confirmed by
pathological analysis or by typical radiological criteria. Patients
were classified as having advanced disease if they were not
eligible for or had disease progression after surgical or
locoregional therapies. Patients must have at least one tumor
lesion that is accurately measured in at least one dimension
according to RECIST. Eligibility criteria also include an
ECOG PS of 0, 1, or 2 and Child pugh class A or B. in addition
there should be adequate hepatic, renal and bone marrow
function.
This open label, phase 2 trial was conducted at Ain
shams University hospitals. All eligible patients were assigned
in a 1:1 ratio to receive continuous oral treatment with either
400 mg of sorafenib (consisting of two 200-mg tablets) twice
daily or oral fluoropyrimidines (capecitabine 20 patients/UFT 6
patients). Capecitabine is given orally at a dose of 1000mg/m2
twice daily. It is given daily for 14 days as part of a 21 days
cycle while UFT is given at a dose of 300 mg/m2 daily
administered orally. It is continued for 28 days and one
treatment cycle is defined as a 5- week treatment.
Median overall survival was 7.05 months in the
sorafenib group and 5.07 months in the oral fluoropyrimidines
group (hazard ratio in the oral fluoropyrimidines group, 2.36;
95% confidence interval, 1.174-4.74; P<0.016). The median progression free survival was 6 months in the sorafenib group
and 4 months in the oral fluoropyrimidines group (P<0.005).
Three patients in the sorafenib group (11.5%) and 1
patient in the oral fluoropyrimidines group (3%) had a partial
response; one patient (3%) had a complete response in the
sorafenib group. Hand–foot skin reaction was more frequent in
the sorafenib group; hyperbilirubinemia was more common in
the oral fluoropyrimidines group and diarrhea was equivalent
between both groups.