The Study On Safety And Clinical Efficacy Of The Combination Of Surgery And Sorafenib In The Treatment Of Intermediate-advanced Hepatocellular Carcinoma

Background and Aim: Majority of HCC patients are diagnosed at a late stage whereno effective treatments are available. Recently, the multikinase inhibitor sorafenib wasfound to improve the survival of patients with advanced HCC. However, the efficacy ofmonotherapy for intermediate-advanced HCC is still not satisfactory and multimodal andcombination therapies have emerged as alternative treatment modalities for HCC.Herein, we aimed to evaluate the safety and efficacy of the combination of sorafenib andsurgery in the treatment of intermediate-advanced HCC.Methods:From June2008to June2011One hundred and eighty-sixty consecutivepatients with intermediate-advanced HCC who were treated with sorafenib were enrolledin this study. For patients with intermediate HCC and advanced HCC, they were bothdivided into two groups: sorafenib group (control group) and sorafenib combined withsurgery group (trial group). Survival rates of the patients were analyzed by theKaplan-Meier method. Cox’s proportional hazards model was used to analyze variablesassociated with survival. Adverse events induced by sorafenib were observed andrecorded.Results：The median follow-up duration was13.0months (range1-41months). Thereare seventy-seven (41.4%) patients with intermediate HCC (BCLC stage B) and onehundred and nine (58.6%) patients with advanced HCC (BCLC stage C). Patients whoreceived liver resection were administered sorafenib with a median of30days afteroperation (range,26-53days). The overall survival was greater in patients withintermediate HCC than patients with advanced HCC (P=0.011). Patients in BCLC stage Bconsisted of69men and8women, with a median age of54years (range,16-74). Amongthe77patients,19patients underwent hepatectomy before the treatment of sorafenib.Among the BCLC stage C patients, there were102men and7women. The median agewas49years (range,16-80).106(97.2%) patients presented with macrovascular invasionand28(25.7%) patients presented with extrahepatic spread.24(22.0%) patients wereinflicted with both macrovascular invasion and extrahepatic spread. Twenty of the109patients underwent surgery before administration of sorafenib. The complication rate was50.0%and the most common complications were ascites and pleural effusion, whichusually resolved with diuretics or paracentesis. No one died during the hospitalization period. Surgery before administration of sorafenib did not contribute to overall survival ofpatients with intermediate HCC (p=0.312). For patients with advanced HCC, survival ofpatients who underwent surgery before sorafenib was signifcantly longer than that ofpatients who received sorafenib alone (15.0months,95%CI12.3-17.7vs.8.0months,95%CI5.5-10.5; p=0.024) and surgery before sorafenib was identified as only predictor ofsurvival for patients with advanced HCC (HR,0.582;95%CI,0.353-0.932; p=0.035). Allpatients experienced at least one adverse event in the duration of sorafenib administration.The most common adverse events were hand-foot-skin reaction (70.9%), diarrhea (55.1%)and fatigue (44.9%) and there were30(16.4%) serious adverse events (grade3/4).17patients received reduced doses of sorafenib (400or600mg/day) and5patientsdiscontinued drug administration,3for hyperbilirubinemia and2for diarrhea.Conclusions：No clinicopathological factors were found to be associated with theprognosis of patients with intermediate HCC. The combination of sorafenib and surgery issafe and significantly prolongs overall survival of patients with advanced HCC.