Epirubicin, cisplatin, 5-FU combination chemotherapy in sorafenib-refractory metastatic hepatocellular carcinoma

Abstract

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/m(2) IV; day 1), cisplatin (60 mg/m(2) IV; day 1), and 5-FU (1000 mg/m(2) IV; 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.

Keywords: 5-FU; Cisplatin; Epirubicin; Hepatocellular carcinoma; Sorafenib.

Figure 1

Survival analysis according to response to chemotherapy. A: The group with controlled disease (PR + SD) showed longer overall survival (OS) outcome than those with progressive disease (PD): median 20.4 mo (full line) vs 4.9 mo (imaginary line); B: In time to progression (TTP), the group with controlled disease groups showed better outcome than those with progressive disease: median 9.4 mo (full line) vs 2.2 mo (imaginary line).

Figure 2

Survival outcomes according to status of primary liver mass. A: The group with stable primary mass showed longer overall survival than those with progressive primary liver mass: median 13.4 mo (full line) vs 5.3 mo (imaginary line); B: In TTP, the group with stable primary mass showed better outcome than those with progressive primary liver mass: median 9.4 mo (full line) vs 2.3 mo (imaginary line). TTP: Time to progression; OS: Overall survival.