Older patients over the age of 65 who have been diagnosed with a malignant brain tumor (glioma) benefit from a chemotherapy with the effective ingredient temozolomide as well as younger patients with this type of cancer. Genetic testing can demonstrate whether older patients will respond to the therapy. These were the results of a clinical study undertaken by a study group of the German Cancer Society’s Neuro-Oncology Working Group (NOA), headed by Prof. Wolfgang Wick, Heidelberg University Hospital and German Cancer Research Center (DKFZ), and Prof. Michael Weller, University Hospital Zurich. The largest study on the treatment of older patients with malignant brain tumors to date has now been published online in the respected medical journal The Lancet Oncology.
Gliomas are especially aggressive tumors. The average survival time with standard therapy is only about a year, although it can also be much longer in individual cases. Nearly 50 % of the patients with gliomas are over the age of 65. In the past, these patients were usually excluded from clinical studies, because the more intensive treatment did not appear to be promising and was expected to produce severe side effects. As a result, older patients only underwent surgery and radiation.
Chemotherapy is as effective as radiotherapy
“Today, many patients over the age of 65 do not have any additional illnesses that would speak against them undergoing chemotherapy,” explained Prof. Wick, Medical Director of the Department of Neurooncology at Heidelberg University Hospital. For this reason, the NOA-08 study was initiated. Involving 23 German centers and one Swiss center, it investigated the effectiveness of chemotherapy in older patients with certain gliomas – the glioblastoma and the anaplastic astrocytoma. As part of the study, the standard treatment, the removal of the tumor followed by radiotherapy, was compared with chemotherapy with temozolomide after surgery.
In addition, the scientists studied the tumor tissue for a specific genetic mutation, the methylation of the gene of the protein O6-methyl-guanyl-methyltransferase (MGMT), which indicates whether a patient will tend to benefit more from radiotherapy or from chemotherapy with temozolomide.
“The results of the NOA-08 study show that after surgery, chemotherapy with temozolomide is as effective as radiotherapy,” explained Prof. Weller, Director of the Department of Neurology at University Hospital Zurich. The study therefore points to a new option for treating older patients with malignant gliomas, namely chemotherapy with temozolomide without radiotherapy.
Genetic testing (biomarkers) can help predict the efficacy of chemotherapy
For the scientists, another finding is even more important: the MGMT genetic modification in the tumor can be used to predict the patient’s response to chemotherapy or radiotherapy. MGMT enhances the efficacy of certain chemotherapies such as temozolomide. Patients with inactive MGMT should therefore always be treated with chemotherapy, while patients with active MGMT should undergo radiotherapy. “This means that for older patients as well, we have a biomarker that we can use to help make treatment decisions,” Prof. Wick said.
A large-scale international study is currently investigating whether the combination of radiotherapy and chemotherapy with temozolomide improves treatment results, which is the case for younger patients. Until the results are available, the scientists explained, testing the methylation of the MGMT promoter, i.e., of the resistance test, should supplement the standard diagnostic repertoire for older patients. This will allow treatment to be more successful thanks to targeted use of radiotherapy or chemotherapy and avoid unnecessary side effects.
Prof Wolfgang Wick, MD; Prof Michael Platten, MD; Christoph Meisner, PhD; Jörg Felsberg, MD; Ghazaleh Tabatabai, MD; Matthias Simon, MD; Prof Guido Nikkhah, MD; Kirsten Papsdorf, MD; Prof Joachim P Steinbach, MD; Michael Sabel, MD; Stephanie E Combs, MD; Jan Vesper, MD; Christian Braun, MD; Prof Jürgen Meixensberger, MD; Ralf Ketter, MD; Regine Mayer-Steinacker, MD; Prof Guido Reifenberger, MD; Prof Michael Weller, MD; for the NOA-08 Study Group of the Neuro-oncology Working Group (NOA) of the German Cancer Society.
Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial.
The Lancet Oncology. Published online before print May 9, 2012.
Prof. Wolfgang Wick
Medical Director, Department of Neurooncology
Heidelberg University Hospital
Im Neuenheimer Feld 400, 69120 Heidelberg
Prof. Michael Weller, Department of Neurology
University Hospital Zurich
Frauenklinikstraße 26, CH-8091 Zurich
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