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Combining Systemic Therapies for Patients with Advanced Liver Cancer

Name of the Trial

Phase III Randomized Study of Sorafenib Tosylate with Versus without Doxorubicin Hydrochloride in Patients with Locally Advanced or Metastatic Hepatocellular Carcinoma (CALGB-80802). See the protocol summary.

Principal Investigator

Dr. Ghassan Abou-Alfa, Cancer and Leukemia Group B

Dr. Ghassan Abou-Alfa
Principal Investigator

Why This Trial Is Important  

Primary liver cancer (hepatocellular carcinoma) is one of the leading causes of cancer death worldwide. Although it is still relatively uncommon in the United States, liver cancer incidence in this country nearly tripled between 1975 and 2008 and continues to rise. Much of the increase in the U.S. population can be traced to rising rates of infection with hepatitis C virus. Other risk factors include alcohol-related cirrhosis of the liver, which accounts for about one-third of U.S. liver cancers, as well as a condition called nonalcoholic steatohepatitis (NASH), which can develop among diabetic and morbidly obese people. As the incidence of diabetes and obesity increases, liver cancer related to NASH is likely to increase as well.

Localized liver cancer that can be surgically removed (resected) is potentially curable, but most patients are not diagnosed until the cancer has become advanced. Until recently, patients with advanced unresectable liver cancer were often treated with the drug doxorubicin, despite little evidence of a survival benefit. In 2007, however, a large randomized phase III trial found that patients with advanced liver cancer who were treated with the targeted drug sorafenib survived nearly 3 months longer than those treated with a placebo.

At the same time, Dr. Abou-Alfa and other researchers were conducting a randomized phase II trial to evaluate the addition of sorafenib to doxorubicin. The analysis of data from the trial showed that patients who received sorafenib plus doxorubicin experienced longer overall survival and progression-free survival than those who received doxorubicin plus a placebo. On the basis of these findings, together with preclinical data that suggest a possible synergistic effect between doxorubicin and sorafenib, researchers decided to compare the combination treatment with sorafenib alone.

In this phase III trial, patients with unresectable, locally advanced or metastatic primary liver cancer who have good liver function (Child-Pugh score A) will receive sorafenib and be randomly assigned to also receive either doxorubicin or no additional therapy. Doctors will compare overall survival between the groups, as well as progression-free survival and tumor responses.  

“Doxorubicin was historically accepted based on the experience of individual doctors, but it was not a proven standard of care,” said Dr. Abou-Alfa. “In this context, and before sorafenib became recognized as a standard of care, we carried out our phase II study comparing doxorubicin and sorafenib to doxorubicin alone. We noticed improved survival but we cannot say if that improvement was entirely due to sorafenib or if doxorubicin also contributed to the benefit. The current study should answer that question.”    

For More Information

See the lists of entry criteria and trial contact information or call the NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The toll-free call is confidential.

  • Posted: March 20, 2012