الفهرس 
EpidemiologyOnly 14 pages are availabe for public view
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Abstract
Advanced hepatocellular carcinoma (HCC) that cannot be treated by loco-regional therapies face a dismal outcome. In Asian countries, the median survival of these patients is in the range of 2–4 months with the best supportive care (Cheng et al., 2009).
Conventional cytotoxic chemotherapy has shown little effect. This limited success of conventional cytotoxic chemotherapy has been attributed to the inherent chemo-resistance of HCC cells, as well as chemo-intolerance of HCC patients as a result of concomitant chronic liver disease (Hsu et al., 2010).
Since 2007, sorafenib has been approved for the indication of unresectable HCC. Sorafenib is generally well tolerated and combination therapy may further improve the efficacy of sorafenib in advanced HCC (Worns et al., 2009).
The combination of molecular targeted therapy with metronomic chemotherapy (low-dose cytotoxic agents administered in a frequent and uninterrupted dosing schedule) can improve the anti-tumor efficacy in advanced HCC. Metronomic chemotherapy may exert its anti-tumor effects through inhibition of angiogenesis. It is significantly less toxic, compared with the conventional, maximum-tolerated-dose chemotherapy. The combination regimens can induce disease stabilization in about 50% of patients with advanced HCC and can be safely administered on an outpatient basis (Hsu et al., 2010).
Our study was conducted in two phases:
First phase where 500 patients with HCC attended to the liver cancer unit, National Liver Institute, Menoufiya University, in the period from April 2012 to July 2013were evaluated to assess their feasibility for therapy.
The 2nd phase of our study was conducted on 31 advanced HCC patients who met the inclusion and exclusion criteria for receiving chemotherapy (sorafenib). They were randomly selected and after an informed consent they were divided into two groups:
Group (A): 16 patients were treated with sorafenib plus tegafur-uracil. In each cycle sorafenib was given in a dose of 400 mg PO twice daily for 35 days while tegafur-uracil (UFT- UFUR) in a dose of 125mg/m2 PO/ BID for 28 days. Patients then had a 7 day off UFT.
Group (B): 15 patients were treated with sorafenib alone. In each cycle sorafenib was given in a dose of 400 mg PO twice daily for 35 days.
Diagnosis of HCC was done according to The American Association For The Study Of Liver Disease (AASLD) recommendations(AASLD, 2010).
After signing an informed consent; all participants were subjected to:
Thorough medical history taking.
Complete clinical examination.
Laboratory investigations: Complete blood count, liver tests, renal function tests, serum electrolytes: sodium and potassium, amylase and lipase. random blood glucose, viral markers: HBs Ag, HCV Ab. AFP.
Radiological investigations: Pelvi-abdominal ultrasound
- Triphasic CT :Abdomen and pelvis.
Electrocardiogram.
Clinical scores: Including ECOG, CTP, CLIP and BCLC.
Our results were :
In the first phase: Out of 500 patients, 67 patients (13.4%) were feasible for radiofrequency, only 38 patients (7.6%) were fit for surgical resection, 8 patients (1.6%) were suitable for liver transplantation, 16 patients (3.2%) were suitable for microwave, 175 patients (35%) were for TACE, only 2 patients (0.4%) were suitable for percutanous ethanol injection (PEI), 57 patients (11.4%) were refered to the best supportive care and 137 patients (27.4%) were feasible for sorafenib therapy.
In the second phase: There were no statistically significant differences between the two studied groups with respect to demographic characteristics, as all the patients were males only one patient in group (B) was female. Three patients in group (A) while five in group (B) were diabetic, and only one patient in each group was hypertensive. Eastern Cooperative Oncology Group (ECOG) performance status was 0 in all patients except one patient in each group with PS 1. All the patients recruited in both groups were chronic hepatitis C virus infection related chronic liver disease as it is endemic in Egypt.
In our study patients in both groups had preserved liver functions with Child Pugh Score (CTP) A in 70% of cases with no difference between two groups. As regard BCLC staging 75% of patients in both groups were BCLC C and 25% of patients were BCLC B and this is explained by absence of screening program for high risk group of HCC.
In group (A) six patients (40%) had prior therapy for HCC either RFA, TACE or hepatic resection. Five patients (30%) had prior TACE, three patients (18%) had prior surgical resection.
In our study the median overall survival in group B(sorafenib) was 10.6 months which is higher than group A (combined sorafenib and UFT) 6.6 months. and this was statistically significant (P value <0.05).
The group treated with BSC had overall survival 10 months and when compared to group (B)was statistically not significant (P value >0.05).While in comparison to group (A) was statistically significant (P value <0.05).
The time to radiological progression in group (B) was 6.6 months compared to 4.8 months in group (A), but was not statisticaly significant (P value <0.05).
There was statistically significant increase in hazard in group (A) than BSC and group (B) (P value <0.05).
The most frequent adverse events were hand foot syndrome and less common were diarrhea, fatigue, abdominal pain, hypertension, weight loss hyperglycemia and hypoglycemia.