Drug & Device Development

Thalidomide of little value for advanced hepatocellular carcinoma

Last Updated: 2005-01-27 12:42:14 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Though well tolerated by most patients, thalidomide treatment of advanced hepatocellular carcinoma (HCC) results in only modest responses, according to a report in the January 1st issue of Cancer.

Animal studies have shown thalidomide to be effective in models of angiogenesis, the authors explain, and clinical studies have shown it to be potentially effective against a variety of cancers.

Dr. Albert Y. Lin from Santa Clara Valley Medical Center, San Jose, California and colleagues investigated whether thalidomide could improve outcomes in 27 patients with unresectable HCC, 31% of whom had metastatic disease at the time of study entry.

With a median daily dose of thalidomide of 300 mg, the authors report, the median time to disease progression was 42 days, and the median survival was 123 days.

Only one patient (3.9%) experienced a partial response, the report indicates, with his alpha-fetoprotein level falling from 34,630 ng/mL to 18 ng/mL after 10 weeks of treatment and with radiographic imaging showing more than 80% decrease in tumor bulk.

"These dramatic results suggest that although they are infrequent, responses of HCC to thalidomide can occur and may be clinically significant," the investigators write.

Patients commonly experienced fatigue, somnolence, and constipation during therapy, the researchers note, but there were few severe adverse events related to thalidomide treatment.

"The results of the current phase II study indicate that thalidomide treatment in patients with unresectable HCC is relatively well tolerated," the authors conclude. "However, the associated response rate is modest."

"In the future," the researchers add, "combining thalidomide or the more potent analogue CC5013 with other targeted agents, such as epidermal growth factor receptor inhibitor, may produce better treatment outcomes."

"The study confirms the original findings of [others] who showed that thalidomide lacks clinical activity in HCC and has relatively increased toxic effects," writes Dr. Scott Wadler from Weill Medical College, Cornell University School of Medicine, New York in a related editorial.

"At many institutions, thalidomide is routinely offered to patients with HCC in lieu of enrollment into clinical trials," Dr. Wadler adds. "The article by Lin and colleagues serves as an important course correction for the academic oncologist."

Cancer 2005;103:1-3,119-125.