Drug Helps Cognitive Function In Brain Tumor Patients After Radiation

After the patients were treated for six months with donepezil (trade name: Aricept), there was a significant improvement in their symptoms, the researchers reported in the March 17 issue of the Journal of Clinical Oncology.

"Each year more than 15,000 Americans are diagnosed with a primary brain tumors, and as many as 200,000 with metastatic brain tumors, nearly all of whom receive radiation therapy," said Edward G. Shaw, M.D. "For survivors of brain tumor radiation, symptoms of short-term memory loss and mood changes similar to those seen in Alzheimer's disease, as well as fatigue, frequently occur, leading to a poor quality of life."

Donepezil, part of a class of drugs called acetylcholinesterase (AChE) inhibitors, "has demonstrated efficacy in mild to severe Alzheimer's disease and vascular dementia," said Stephen R. Rapp, Ph.D., professor of psychiatry and behavioral medicine and senior author on the paper. It is approved by the U.S. Food and Drug Administration for that purpose.

"The results of this initial study encourage continued investigation of donepezil and other AChE inhibitors," Rapp said.

The research team is planning a clinical trial in which treatment of brain tumor patients with donepezil will be compared to an inert placebo, and neither the doctor nor the patient will know which pill they received until the study is completed.

"To our knowledge, this is the first study of an AChE inhibitor or any other drug administered to long-term survivors of partial or whole brain radiation therapy in an attempt to reduce the symptoms associated with a brain tumor and its treatments," said Shaw, professor and chairman of the Department of Radiation Oncology and a co-author.

"The pretreatment assessment of thinking, memory, mood and energy level revealed symptoms that clearly affected quality of life," Shaw said.

The researchers decided to try donepezil after observing that radiation-induced brain injury resembles Alzheimer's disease and other forms of dementia not only in the clinical symptoms but also in what is seen with brain imaging, particularly with magnetic resonance imaging (MRI) and positron emission tomography (PET).

The team hypothesized that radiation therapy for brain tumors resulted in injury to neurons that in turn caused a deficiency of a brain chemical called acetylcholine. They thought use of an AChE inhibitor -- such as donepezil -- might increase the acetylcholine level in the brain, decrease cognitive symptoms and improve mood and quality of life. Their study indicated it did.

"Additional research is needed to further evaluate donepezil and other AChE inhibitors in this population." Rapp said.

The other members of the team were Robin Rosdhal, R.N., O.C.N., and Mike E. Robbins, Ph.D., both from radiation oncology, and Ralph B. D'Agostino Jr., Ph.D., James Lovato, M.S. and Michelle J. Naughton, Ph.D., all from public health sciences.