Drug may reduce cognitive decline following radiation for brain metastases

Memantine, which is already approved to help improve cognition in some patients with dementia, may limit declines in memory and cognitive function in patients who are undergoing whole-brain radiation therapy (WBRT) to treat cancer that has spread to the brain.

More than 60% of patients with brain metastases who undergo WBRT experience problems with cognitive function within 4 months after completing treatment. This trial sought to determine if memantine could prevent memory decline in patients, and it was not testing if the drug improved progression-free or overall survival.

This phase III randomized trial enrolled more than 550 patients who either received memantine or placebo during WBRT and for 6 months afterwards. The researchers assessed the patients' memory and other cognitive functions, such as the ability to process information and make decisions, before and after treatment. Many patients in the trial died or had cancer that continued to progress, however, so after 24 weeks only 149 patients could be evaluated. Because the patients whose disease progressed often refused testing, the evaluation was largely of patients who had not progressed.

In the patients treated with memantine, memory decline took longer to appear and was less severe, although the improvement was not statistically significant. However, the risk of cognitive decline fell 17%, which was statistically significant.

“Although memantine was discontinued at 6 months, the effect on cognitive function was maintained for the duration of the trial, suggesting that memantine may be preventing radiation injury rather than simply treating cognitive dysfunction,” explained lead investigator Nadia Laack, MD, of the Mayo Clinic Cancer Center.

The trial's results mean that memantine will likely now be used as standard therapy for patients undergoing WBRT to treat brain metastases, explained Laack, who added, “We do feel that this is going to impact practice tomorrow and that, for future trials, memantine will be the standard against which other agents are tested.”

This research was presented at the American Society for Radiation Oncology (ASTRO) annual meeting, October 28-31, 2012, in Boston, Massachusetts.
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