First-line gemcitabine and oxaliplatin (GEMOX) plus sorafenib, followed by sorafenib as maintenance therapy, for patients with advanced hepatocellular carcinoma: a preliminary study.

BACKGROUND: Because of the poor prognosis of unresectable or metastatic hepatocellular carcinoma there is a need for effective systemic therapy. The purpose of this study was to assess the efficacy and safety of gemcitabine and oxaliplatin (GEMOX) combined with sorafenib, as first-line therapy, followed by sorafenib as maintenance therapy for patients with advanced hepatocellular carcinoma (HCC).

METHODS: In this open-label, multicenter, single-group, prospective study, eligible patients with advanced HCC received oral sorafenib 400 mg twice daily, gemcitabine 1,000 mg/m(2) intravenously (i.v.) on day 1 and oxaliplatin 85 mg/m(2) i.v. on day 2 every 14 days for up to six cycles. Patients without disease progression were then treated further with sorafenib as maintenance therapy until disease progression.

RESULTS: All forty-nine patients completed six cycles of combined GEMOX and sorafenib therapy. The objective response was 26.5 %. The median time to progression was 10.3 months (95 % CI: 8.7-11.9 months) and median overall survival was 15.7 months (95 % CI: 13.0-18.4 months). During the combination therapy, the most common grade 3/4 hematologic toxicity was neutropenia (22.4 %, 11/49 patients) and thrombocytopenia (14.3 %, 7/49 patients); grade 3/4 non-hematologic toxicity was fatigue (22.4 %, 11/49 patients) and appetite loss (18.4 %, 9/49 patients). During the maintenance therapy, grade 3/4 adverse events were nonhematologic toxicity, for example fatigue (16.0 %, 4/25 patients) and appetite loss (16.0 %, 4/25 patients).

CONCLUSIONS: GEMOX combined with sorafenib as first-line therapy followed by sorafenib as maintenance therapy was effective with manageable toxicity for patients with advanced hepatocellular carcinoma. However, the results should be further validated in controlled phase II trials.