Alzheimer’s Drug Suppresses Cognitive Decline in Brain Tumor Patients Who Undergo Whole Brain Radiotherapy

An N-Methyl-D-aspartate receptor antagonist called memantin, which is usually prescribed to Alzheimer’s disease (AD) patients, has been shown to slow cognitive decline in brain cancer patients who receive whole brain radiation therapy (WBRT).

The findings were presented October 31, 2012, at the American Society for Radiation Oncology’s (ASTRO’s) 54th annual meeting, held October 2012 in Boston (MA, USA). The phase III trial assessed the possible protective effects of memantine on cognitive function in 508 patients with brain tumors who received WBRT between March 2008 and July 2010. In addition to cognitive function, the study examined the length of time before suffering cognitive decline, overall survival (OS), and progression-free survival (PFS). Patients received WBRT of 37.5 Gy in 15 fractions and they were randomized to receive placebo or a 20-mg dose of memantine a day within three days of initiating radiotherapy for 24 weeks. Results demonstrate that memantine delays cognitive decline of recognition memory, global and executive function, and processing speed regions of the brain.

Patients in the memantine group experienced a 17% relative reduction in cognitive decline at 24 weeks compared to those in the placebo group. Patients’ cognitive function as assessed utilizing the Controlled Oral Word Association test at 8 and 16 weeks and the Trail Making Test Part A at 24 weeks also revealed fewer patients in the memantine group experienced decline. Patients were also evaluated at 24 weeks with the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-R DR), which showed a median decline of 0 for patients who received memantine in comparison to those in the placebo group, who had a decline of -2. The trends of all three cognitive tests for the 149 eligible patients who survived 24 weeks indicate that the memantine group produced superior results than the placebo at all points. There was no difference in patients’ PFS or OS between the treatment arms.

Patients in the study included adults who had brain metastases and were categorized by recursive partitioning analysis in either class I or II with or without or surgical resection or prior radiosurger. Patients underwent standardized tests of cognitive function, which were performed at baseline, eight, 16, 24, and 52 weeks. Just 32% of patients completed the drug therapy and evaluations principally because of poorer than estimated survival and progressive disease, which led to poor compliance with the treatment protocol. Patients in both groups reported similar levels of grade 3 and 4 toxicities, including headache, fatigue, hair loss, and nausea.

“We are excited to see that adding memantine to the treatment plan for brain tumor patients helps preserve their cognitive function after whole brain radiotherapy even six months after treatment,” said Nadia N. Laack, MD, coauthor of the study and a radiation oncologist at the Mayo Clinic (Rochester, MN, USA). “Our findings suggest that memantine may prevent the changes that occur in the brain following radiation therapy, impacting future treatment practices for these patients and suggest a role for further study in other patient populations receiving radiation to the brain.”

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