NEW YORK (Reuters Health) - It is possible to predict which patients with glioblastoma will benefit from temozolomide chemotherapy by determining the methylation status of the DNA repair gene O-6-methylguanine DNA methyltransferase (MGMT) in the tumor, according to findings presented at a cancer conference in Switzerland.
Temozolomide preferentially targets glioblastoma with a methylated or silent MGMT promotor gene and hence an impaired DNA repair system.
Dr. Monika Hegi from University Hospital of Lausanne, explained that “MGMT repairs damage that is done by temozolomide. Thus it reverses part of the beneficial effect of the drug.” There is a “significant survival advantage” for glioblastoma patients with methylated MGMT, she reported to the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics underway in Geneva.
The conference is sponsored by the European Organization for Research and Treatment of Cancer (EORTC), the U.S. National Cancer Institute (NCI) and the American Association for Cancer Research (AACR).
Temozolomide, approved in 1999 for relapsed glioblastoma, is the first chemotherapy in 30 years proven to be effective for glioblastoma, which accounts for up to 15% of all brain cancers.
Dr. Hegi’s team determined the methylation status of MGMT in 206 glioblastoma biopsies collected from patients participating in a large trial of temozolomide added to standard radiotherapy. They observed methylated MGMT in 45% of the biopsies.
In a subset of 106 patients treated with both temozolomide and radiotherapy in the trial, the two-year survival rate was significantly higher among the 46 patients with methylated compared with the 60 patients with non-methylated MGMT promotor (46% versus 13.8%).
At a news briefing, Dr. Hegi said that the methylation status of MGMT is a “predictive factor for glioblastoma patients that should be taken up into the clinic. It is an easy test to do and will help to identify the patients that are likely to profit from temozolomide.”
“For the over 50% of patients who have no methylation of this gene,” she continued, “they derive little if any benefit from temozolomide.” They may benefit from alternative treatments which are not as yet established.
MeSH Headings:Alkylation: Biological Sciences: Biology: Brain Neoplasms: Chemistry: Chemistry, Organic: Genetics: Genetics, Biochemical: Methylation: Molecular Biology: Neoplasms: Neoplasms by Site: Nervous System Diseases: Nervous System Neoplasms: Physical Sciences: Central Nervous System Neoplasms: DNA Methylation: Biological Sciences: Diseases: Physical SciencesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
