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Erlotinib Shows Early Activity in Liver Cancer

Erlotinib Shows Early Activity in Liver Cancer

HOUSTON-Erlotinib (Tarceva) is active in hepatocellular carcinoma and is well tolerated, according to interim findings of a phase II trial at The University of Texas M.D. Anderson Cancer Center. The results also suggest that higher expression of the epidermal growth factor receptor (EGFR) may be correlated with response to the drug, said Melanie Thomas, MD, an assistant professor in the Department of GI medical oncology at M.D. Anderson, who discussed the findings in a poster presentation (abstract 4038). The trial is designed to accrue 80 patients who are stratified into subgroups according to high or low expression of EGFR, the target of erlotinib. With 33 of 80 patients accrued to the current trial, 25% had reached the primary study endpoint of progression- free survival at 16 weeks. Median survival was 6 months. There were two minor responses among 22 evaluable patients, for a response rate of 9%. Response did not correlate with other factors, such as age, sex, presence of cirrhosis, etiology, or alpha fetoprotein expression. EGFR Expression Survival Trend Of the eight patients who were progression- free at 16 weeks, six had high EGFR expression in tumor cells and two had low expression. While not statistically significant, the difference suggests that expression may be a factor. "There did seem to be a trend toward correlation of survival with high EGFR expression," said Keith E. Stuart, MD, director of hepatobiliary and gastrointestinal oncology at Beth Israel Deaconess Medical Center, Boston, in discussing the study. The drug appeared to be safe and well tolerated. Grade 3 toxicities occurred in about one-fourth of patientsand included abdominal pain, anemia, increased bilirubin and AST (aspartate aminotransferase), skin infection, vomiting, and diarrhea. All responding patients developed skin rash, a common event associated with erlotinib and other tyrosine kinase inhibitors. In discussing this trial, Dr. Stuart noted that it was one of many studies seeking new approaches to liver cancer. Hepatocellular carcinoma is oneof the most common causes of death in the world, he said, and "survival is uniformly miserable." Five-year survival rates in the United States have gone from 2% in the late 1970s to 5% in the late 1990s. Most patients are not eligible for resection, he added, and systemic therapies to date have had little impact on the disease. Because hepatocellular carcinomas are hypervascular tumors, treatments targeted at proteins that control angiogenesis are of interest. These include drugs that target EGFR, such as erlotinib and gefitinib (Iressa), and those that target the vascular endothelial growth factor, such as bevacizumab (Avastin). A trial of erlotinib and bevacizumab combined to treat hepatocellular carcinoma is being instituted at M.D. Anderson, Dr. Thomas said, and if the combination shows efficacy, the next step could be to combine the two drugs with chemotherapy.

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