Memantine with whole brain radiation therapy slows cognitive decline

November 2, 2012 - Memantine, an N-Methyl-D-aspartate receptor antagonist typically prescribed to Alzheimer’s patients, slows cognitive decline in brain cancer patients who receive whole brain radiation therapy (WBRT), according to research presented today at the American Society for Radiation Oncology’s (ASTRO’s) 54th Annual Meeting.

WBRT for brain metastases in this case* correlated with survival and improved neurocognitive function.
*Regression After Whole-Brain Radiation Therapy for Brain Metastases Correlates Jing Li. With Survival and Improved Neurocognitive Function. J Clin Oncol. 2007;10:1260-1266.

In a recent study, patients in the memantine group experienced a 17% reduction in cognitive decline at 24 weeks compared to those in the placebo group. “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, co-author of the study and a radiation oncologist at the Mayo Clinic in Rochester, MN.

The phase III trial evaluated the potential 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 analyzed the length of time before experiencing cognitive decline, overall survival (OS) and progression-free survival (PFS). Patients received WBRT of 37.5 Gy in 15 fractions and were randomized to receive placebo or a 20mg dose of memantine per day within 3 days of initiating radiotherapy for 24 weeks. Results demonstrate that memantine delays cognitive decline in areas of recognition memory, global function, executive function and processing speed.

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 indicated 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 yielded better results than the placebo at all points. There was no difference in patients’ OS or PFS between the treatment arms.

Patients in the study included adults who exhibited brain metastases and were stratified by recursive partitioning analysis in either Class I or II with or without prior radiosurgery or surgical resection. Patients underwent standardized tests of cognitive function, which were performed at baseline, eight, 16, 24 and 52 weeks. Only 32 percent of patients completed the drug therapy and assessments mainly due to 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 hair loss, fatigue, headache and nausea.

“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,” indicated Dr. Laack.

The abstract, “Memantine for the Prevention of Cognitive Dysfunction in Patients Receiving Whole-brain Radiation Therapy (WBRT): First Report of RTOG 0614, a Placebo-controlled, Double-blind, Randomized Trial,” was presented in detail during the plenary session at ASTRO’s 54th Annual Meeting.

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