JAMA Logo Hepatocellular [liver] carcinoma (HCC), an inoperable advanced liver cancer apparently provides a median survival of not more than just a few months. Usually patients with HCC may be subjected to doxorubicin, but the help received is unclear. A groundbreaking study suggests that inclusion of doxorubicin together with agent sorafenib in the treatment of inoperable advanced liver cancer enhances overall survival and progression-free survival rates.

A randomized, phase 2 study was undertaken on 96 advanced HCC patients from April 2005 to October 2006. While 76 percent were men, the median age was 65 years. Participants were randomly selected to either receive doxorubicin intravenously and sorafenib every 21 days or placebo orally twice a day. By the time of the follow-up which ended in April 2008, 2 patients belonging to the placebo group were given sorafenib. 51 total time-to-disease progression events were registered in 24 patients from the doxorubicin plus sorafenib group and 27 subjected to doxorubicin along with placebo.

Investigators comment, “In summary, among patients with advanced HCC, treatment with sorafenib doxorubicin compared with doxorubicin plus placebo resulted in greater median time to progression, overall survival, and progression-free survival. The degree to which this improvement may represent synergism between sorafenib and doxorubicin remains to be defined. This trial has served as the basis for the ongoing phase 3 trial of sorafenib plus doxorubicin vs. sorafenib alone.”

The time for disease progression was a median of 6.4 months for patients taking a combination of doxorubicin plus sorafenib and 2.8 months for those on doxorubicin with placebo. In the study 25 from the doxorubicin-sorafenib group and 38 of the doxorubicin-placebo group died. The median of overall survival was 13.7 months in doxorubicin plus sorafenib group and 6.5 months among those provided with doxorubicin together with placebo. Risk of death in patients treated with doxorubicin and sorafenib was apparently reduced by 51 percent.

Total progression-free survival events were 32 in the doxorubicin-sorafenib group and 38 in the doxorubicin-placebo group. The median progression-free survival supposedly was 6 months in doxorubicin plus sorafenib group and 2.7 months among those who received doxorubicin plus placebo. A 46 percent reduction in the risk of progression or death was reported by patients treated with doxorubicin plus sorafenib. Ghassan K. Abou-Alfa, M.D., of Memorial Sloan-Kettering Cancer Center, New York, and colleagues pointed out that toxicity of both the medications were probably the same.

The study was published in the November 17 issue of JAMA.