Erlotinib Shows Early Activity in Liver Cancer

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Oncology NEWS InternationalOncology NEWS International Vol 14 No 8
Volume 14
Issue 8

This supplement to Oncology News International includes more than 15 reportson presentations made at the 41st annual meeting of the American Society of Clinical Oncology.Reviews focus on the use of targeted agents in non–small-cell lung cancer and other solid tumors,evaluating the novel therapies bevacizumab, cetuximab, bortezomib, erlotinib, and gefitinib, aloneand/or in combination with other chemotherapy agents. Continuing medical education credit isavailable by completing a post-test and evaluation online at www.cancernetwork.com/cme.

HOUSTON-Erlotinib(Tarceva) is active in hepatocellularcarcinoma and is well tolerated, accordingto interim findings of a phaseII trial at The University of Texas M.D.Anderson Cancer Center. The resultsalso suggest that higher expression ofthe epidermal growth factor receptor(EGFR) may be correlated with responseto the drug, said Melanie Thomas,MD, an assistant professor in theDepartment of GI medical oncology atM.D. Anderson, who discussed thefindings in a poster presentation (abstract4038).The trial is designed to accrue 80patients who are stratified into subgroupsaccording to high or low expressionof EGFR, the target of erlotinib.With 33 of 80 patients accrued tothe current trial, 25% had reached theprimary study endpoint of progression-free survival at 16 weeks. Mediansurvival was 6 months. There were twominor responses among 22 evaluablepatients, for a response rate of 9%.Response did not correlate with otherfactors, such as age, sex, presence ofcirrhosis, etiology, or alpha fetoproteinexpression.EGFR ExpressionSurvival TrendOf the eight patients who were progression-free at 16 weeks, six had highEGFR expression in tumor cells andtwo had low expression. While notstatistically significant, the differencesuggests that expression may be a factor."There did seem to be a trendtoward correlation of survival with highEGFR expression," said Keith E. Stuart,MD, director of hepatobiliary andgastrointestinal oncology at Beth IsraelDeaconess Medical Center, Boston,in discussing the study.The drug appeared to be safe andwell tolerated. Grade 3 toxicities occurredin about one-fourth of patientsand included abdominal pain, anemia,increased bilirubin and AST (aspartateaminotransferase), skin infection,vomiting, and diarrhea. Allresponding patients developed skinrash, a common event associated witherlotinib and other tyrosine kinase inhibitors.In discussing this trial, Dr. Stuartnoted that it was one of many studiesseeking new approaches to liver cancer.Hepatocellular carcinoma is oneof the most common causes of deathin the world, he said, and "survival isuniformly miserable." Five-year survivalrates in the United States havegone from 2% in the late 1970s to 5%in the late 1990s. Most patients are noteligible for resection, he added, andsystemic therapies to date have hadlittle impact on the disease.Because hepatocellular carcinomasare hypervascular tumors, treatmentstargeted at proteins that control angiogenesisare of interest. These includedrugs that target EGFR, such aserlotinib and gefitinib (Iressa), andthose that target the vascular endothelialgrowth factor, such as bevacizumab(Avastin).A trial of erlotinib and bevacizumabcombined to treat hepatocellularcarcinoma is being instituted at M.D.Anderson, Dr. Thomas said, and if thecombination shows efficacy, the nextstep could be to combine the two drugswith chemotherapy.

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