Transarterial Chemoembolization Combined With Sorafenib In Intermediate/Advanced Hepatocellular Carcinoma: Safety, Efficacy And Prognosis Factors

Part ⅠThe Safety of Transarterial Chemoembolization Combined withSorafenib in Intermediate/Advanced Hepatocellular CarcinomaBackground and Aim: Hepatectomy, local ablation and liver transplantation has beenaccepted as the conventional curative treatments for Hepatocellular carcinoma (HCC), butonly about30%of patients are amenable to such curative treatments at the time of diagnosis.Transarterial chemoembolization (TACE) and sorafenib are main palliative treatmentsperformed in the therapy of intermediate/advanced HCC. The outcome, however, is not verysatisfied for HCC patients treated with TACE or sorafenib monotherapy. So far, some studieshave found the anti-angiogenesis of sorafenib has the potential to decrease the rate of tumorneo-angiogenesis which is one of the principal causes contributing to the failure of TACE.Our main aim is to evaluate the safety of sorafenib in patients with intermediate/advancedHCC who are undergoing TACE through retrospective analysis.Methods: From July2008to December2011, a total of65patients who were performedTACE and sorafenib were enrolled in the study for a retrospective analysis per the EasternHepatobiliary Surgery Hospital. The patients were followed up by clinic reexamination ortelephones to evaluate the adverse events (AEs), which is graded according to the CommonTerminology Criteria for Adverse Events (CTCAE) version3.0.Results: All patients treated with sorafenib experienced at least one drug-related adverseevent during the study. The most common AEs were hand-foot skin reaction (55.4%),diarrhoea (47.7%) and rash (29.2%). Most of the grade3and4AEs included hand-foot skinreaction (9.2%) and diarrhoea(7.8%). No toxicity-related death was recorded.Conclusion: The combination of sorafenib and TACE is well tolerated inintermediate/advanced HCC patients. PART ⅡThe Efficacy of Transarterial Chemoembolization Combined withSorafenib in Intermediate/Advanced Hepatocellular CarcinomaBackground and Aim: The safety of TACE combined with sorafenib has been demonstratedby several clinical trials. Nevertheless, the data on overall survival is little. Our main aim is toevaluate the efficacy of TACE combined with sorafenib in patients withintermediate/advanced HCC through retrospective comparative analysis.Methods: From July2008to December2011, a total of114patients were enrolled in thestudy for a retrospective comparative analysis per the Eastern Hepatobiliary Surgery Hospital.57patients treated with TACE plus sorafenib were included in the TACE+sorafenib group andother57patients with similar baseline characteristics who received TACE alone were selectedin the TACE group. All patients with Barcelona Clinic Liver Cancer (BCLC) stage C (n=59)had the macrovascular invasion but no extrahepatic metastasis prior to first TACE. Theprimary endpoint of the study was the overall survival in the study.Results: The median overall survival time was13months (95%CI:9.8,16.2months) forTACE+sorafenib group and8months (95%CI:6.2,9.8months) for the TACE group(P=0.008). The1-year survival rates in the TACE+sorafenib group and TACE group were45.6%and35.1%, respectively, and their2-year survival rates were32.4%and17.6%,respectively.Conclusion: The combination of sorafenib and TACE resulted in significantly longer overallsurvival time than TACE monotherapy in intermediate/advanced HCC patients withoutextrahepatic metastasis. PART ⅢA Study of Prognostic Factors in Patients withIntermediate/Advanced HCC Treated with TACEAim: To investigate the major prognostic factors in intermediate/advanced HCC patientstreated with TACE.Methods: From July2008to December2011, a total of114HCC patients who wereperformed TACE were enrolled in the study for a retrospective analysis per the EasternHepatobiliary Surgery Hospital. The primary endpoint of the study was the overall survival inthe study. The Mantel-Cox test was used to determine univariate prognostic factors, and theCOX regression model was used to analyse the multivariate prognostic factors.Results: In multivariate analysis, independent prognostic factors for longer survival included:different treatments (HR:0.484, P=0.002), BCLC stage/macrovascular invasion (HR:2.255,P=0.002), tumor size (HR:2.147, P=0.001), prealbumin levels (HR:0.586, P=0.040) andHBV reactivation (HR:2.137, P=0.001). For patients with intermediate/advanced HCC, thetreatment of TACE combined sorafenib and prealbumin≥170mg/L can decrease the risk ofdeath.Conclusion: Careful monitoring HBV-DNA and serum prealbumin level is crucial to improvethe prognosis of intermediate/advanced HCC patients who were treated with TACE.