The genetic predictive test on tumour biopsies to identify who will benefit from the drug could be carried out fairly easily in any genetics laboratory and takes only two to three days, although the availability and quality of the tissue is an important issue. If implemented widely it would mean that temozolomide would become a targeted treatment.
Dr. Monika Hegi told the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Geneva today (Wednesday 29 September) that the key to predicting which patients will gain from temozolomide was a gene called O-6-methylguanine-DNA methyltransferase (MGMT) which is involved in DNA repair and its respective methylation status in the patient's tumour.
Methylation is one of the ways that cells control which genetic information they will use. If the MGMT promoter is methylated, the MGMT gene is silenced and this means that no MGMT repair enzyme will be produced, thus preventing correction of faults in the DNA.
Dr. Hegi, head of the laboratory of tumour biology and genetics at the Department of Neurosurgery, University Hospital of Lausanne, Switzerland, said that of a total of 573 patients, biopsies from 206 glioblastoma patients had been tested successfully so far in a seven-country trial organised by the EORTC and National Cancer Institute of Canada Clinical Trials Group (NCIC). 45% had a methylated MGMT promoter, meaning that the MGMT gene was silent and their DNA repair system was impaired.
In this tested group 106 of the patients have been treated with radiotherapy and temozolomide. There was a 46% survival rate at two years for the 46 patients in the group who had a
Contact: Margaret Willson
European Organisation for Research and Treatment of Cancer