Treating patients with advanced hepatocellular carcinoma (HCC) with a combination of doxorubicin and sorafenib may increase median time to progression, overall survival, and progression-free survival compared with doxorubicin alone, a new study suggests.
Leonard B. Saltz, MD, of Memorial Sloan-Kettering Cancer Center, New York, and his associates enrolled 96 patients with advanced HCC, Eastern Cooperative Oncology Group performance status 0 to 2, Child-Pugh A status who had not received prior systemic therapy in a phase 2 multinational study. Patients were randomly assigned to treatment with 60 mg/m2 of doxorubicin intravenously every 21 days plus either 400 mg of the multikinase inhibitor sorafenib or placebo orally twice a day. The trial was stopped after an unplanned early analysis for efficacy by an independent data monitoring committee.
Median time to progression was 6.4 months in patients who received sorafenib plus doxorubicin compared with 2.8 months in the doxorubicin-placebo group. Of the 96 patients, 63 died: 25 in the doxorubicin-sorafenib group and 38 in the doxorubicin-placebo group. Median overall survival was 13.7 months in the doxorubicin-sorafenib group versus 6.5 months in the doxorubicin-placebo group, and progression-free survival was 6.0 months and 2.7 months in these groups, respectively.
Adverse effects of the two agents were additive and similar to what would be expected with each agent used alone.
The extent to which the improvement in median time to progression, overall survival, and progression-free survival seen with the combination of sorafenib and doxorubicin is due to synergism of the two drug remains to be determined, the researchers note. Based on the results of the study, a phase 3 trial of sorafenib plus doxorubicin vs sorafenib alone is being conducted.