الفهرس | Only 14 pages are availabe for public view |
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. |