AIM:To evaluate the clinical efficacy and safety of epirubicin,cisplatin,and 5-FU combination chemotherapy for the sorafenib-refractory metastatic hepatocellular carcinoma(HCC).METHODS:From April 2009 to June 2012,31 patients who were diagnosed with metastatic and progressive HCC after sorafenib treatment were retrospectively reviewed.Patients were treated with the combination of epirubicin(50 mg/m2Ⅳ;day 1),cisplatin(60 mg/m2Ⅳ;day 1),and 5-FU(1000 mg/m2Ⅳ;day 1-3)[Epirubicin,cisplatin,5-FU combination(ECF)],repeated every 4 wk.RESULTS:The overall response rate was 12.9%.Patients who responded to ECF chemotherapy showed a longer overall survival(OS)and time to progression(TTP)relative to those in the non-responder group(OS:20.4 mo vs 4.9 mo,P<0.001,TTP:9.4 mo vs 2.2 mo,P<0.001).Patients with a stable primary liver mass also exhibited a longer OS and TTP relative to those with progressive disease(OS:13.4 mo vs 5.3 mo,P=0.003;TTP:9.4 mo vs 2.3 mo,P=0.003).The most common hematologic toxicity was thrombocytopenia(87.2%),and the incidence of grade 3-4 neutropenia was 53.9%.Age older than 60,a stable primary mass,and a good response to chemotherapy were prognostic factors for OS and TTP.CONCLUSION:This combination cytotoxic chemotherapy can serve as another treatment option after sorafenib failure for the subset of patients with advanced metastatic HCC. AIM: To evaluate the clinical efficacy and safety of epirubicin, cisplatin, and 5-FU combination chemotherapy for the sorafenib-refractory metastatic hepatocellular carcinoma (HCC). METHODS: From April 2009 to June 2012,31 patients who were diagnosed with metastatic and progressive HCC after sorafenib treatment were retrospectively reviewed. Patients were treated with the combination of epirubicin (50 mg / m2 IV; day 1), cisplatin (60 mg / m2 IV; day 1), and 5-FU 3) [Epirubicin, cisplatin, 5-FU combination (ECF)], repeated every 4 wk .RESULTS: The overall response rate was 12.9%. Patients who responded to ECF chemotherapy showed a longer overall survival (OS) and time to progression TTP) relative to those in the non-responder group (OS: 20.4 mo vs 4.9 mo, P <0.001, TTP: 9.4 mo vs 2.2 mo, P <0.001) TTP relative to those with progressive disease (OS: 13.4 mo vs 5.3 mo, P = 0.003; TTP: 9.4 mo vs 2.3 mo, P = 0.003) .The most common hematologic toxicity was thrombocytopenia (87.2%), and the incidence of grade 3-4 neutropenia was 53.9%. Age older than 60, a stable primary mass, and a good response to chemotherapy were prognostic factors for OS and TTP.CONCLUSION: This combination cytotoxic chemotherapy can serve as another treatment option after sorafenib failure for the subset of patients with advanced metastatic HCC.