Early tests indicate that the monoclonal antibodies cetuximab and erlotinib may be effective for one form of glioblastoma.
After finding the deletion mutation within the EGFR carboxyl-terminus domain (CTD) that causes this specific brain tumor, which affects fewer than 5% of all patients with glioblastoma, researchers tested the effectiveness of both erlotinib and the stronger cetuximab to treat and eradicate the tumors. Both drugs prolonged survival in animal studies, according to the team of researchers at the University of California San Diego School of Medicine and Moores UCSD Cancer Center, in collaboration with colleagues in Boston and South Korea.
"What we've found is that actually the drugs are very receptive in certain brain cancers that have specific mutations that make them really responsive to those drugs," Santosh Kesari, MD, PhD, the co-corresponding author of the study published in Cancer Research (2011:71;7587–7596), said in a telephone interview. But, because the gene mutation identified is associated with fewer than 5% of all brain tumors, only that limited population of glioblastoma patients would potentially benefit from the drug.
The researchers analyzed 400 glioblastoma patient samples from The Cancer Genome Atlas (TCGA) database, sequenced the DNA of tumors with amplification of the EGFR, and found the deletion of the exon 27 mutation to be associated with those specific tumors. And because both cetuximab and erlotinib have been responsive on other types of lung and colon cancers with the same EGFR proteins (by binding to specific sites on the proteins to stop tumor growth), these drugs were chosen for initial testing.
Cetuximab, which functions like erlotinib, but is stronger, yielded more successful results, and is the drug the researchers would like to continue investigating with clinical trials. A total of 90% of mice xenograft with the EGFR CTD deletion mutants given doses of cetuximab survived the duration of the 92-day test period, and 100% of the mice given the drug for an additional 60 days were still alive at the end of that period without any sign of the initial tumor.
SANTOSH KESARI, MD, ...Image Tools
The researchers are now working to validate these findings reviewing past trials and testing only cetuximab in only patients with the mutation (previous studies had included patients with all types of glioblastoma).
© 2012 Lippincott Williams & Wilkins, Inc.