December 2012, Vol 1, No 6

← Back to Issue

Memantine Delays Cognitive Decline in Patients With Brain Metastases Treated With Whole-Brain Radiation

Phoebe Starr


Memantine delayed cognitive decline in patients treated with whole-brain radiation therapy (WBRT) for brain metastases, according to results of a randomized phase 3 trial presented at the 54th Annual Meeting of ASTRO.

Cognitive decline is common with WBRT, occurring in 50% to 60% of patients 4 months following radiation treatment. Since the mechanism of radiation-induced cognitive decline appears to be similar to that of vascular or Alzheimer’s dementia, the researchers postulated that memantine, a drug used to treat Alzheimer’s disease, would be of benefit in patients treated with WBRT.

“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 6 months after treatment. 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 patients receiving radiation to the brain,” said lead author Nadia N. Laack, MD, radiation oncologist at the Mayo Clinic in Rochester, MN.

Formal discussant of this trial, Vinai Gondi, MD, Associate Director of the CDH Proton Center in Warrenville, IL, called this study “a good first step” in understanding the cognitive changes resulting from brain radiation and the role of memantine in preventing or delaying them. He said that the effect of memantine was modest in this trial, and that other strategies to improve cognitive effects of radiation are being pursued by researchers.

The study included 508 patients with brain metastases who received WBRT between March 2008 and June 2010. WBRT was delivered as 37.5 Gy in 15 daily fractions. Patients were randomized to memantine 20 mg/day or placebo within 3 days of the start of radiation therapy. Six domains of cognitive function (memory, processing speed, executive function, global function, self-reported cognitive function, and quality of life) were assessed by different instruments at baseline and weeks 8, 16, 24, and 52. The primary end point was memory as assessed by the Hopkins Verbal Learning Test-Revised (HVLT-R).

Compliance with the cognitive testing protocol was suboptimal, with 32% of patients completing drug therapy and cognitive assessments. The reasons for noncompliance appeared to be death, disease progression, and difficulty in getting patients to stay longer during a clinic visit or in physicians scheduling the extra 20 minutes to 1 hour required for cognitive testing. Of the 508 patients randomized to the 2 arms, only 149 were available for analysis at 24 weeks.
For the primary end point, memantine reduced the decline in HVLT-R delayed recall, with a median decline of 0 versus –2 for placebo at 24 weeks, with a statistical significance of P=.059, “teetering on the edge of significance,” according to Laack.

At 24 weeks, memantine reduced the relative risk of cognitive decline by 17% versus placebo (P=.01) and reduced the rate of decline in cognitive, executive, and global function as well as processing speed (P<.01).

Patients in both groups experienced similar rates of grade 3 and 4 toxicities, including alopecia, fatigue, headache, and nausea.

The investigators plan to evaluate the effect of memantine on overall survival and progression-free survival in these patients. Also, tissue specimens will be studied to identify biomarkers of cognitive decline as well as of response to memantine.

Uncategorized - December 20, 2012

Activating HER2 Mutations Found in HER2-Negative Patients

Approximately 4000 breast cancer patients in the United States harbor HER2 mutations amenable to treatment with anti-HER2 therapy but are not receiving it because they are not HER2-positive on fluorescence in situ hybridization or immunohistochemical testing. However, genomic sequencing can identify patients with these mutations, who are likely to benefit [ Read More ]

The Last Word - December 21, 2012

Companion Diagnostics and the Paradoxical Return of the Blockbuster Drug

In my article in the inaugural issue of Personalized Medicine in Oncology, I got a bit dogmatic in proclaiming that personalized medicine (PM) drug treatment selectivity spelled the end of population-based medicine, and with it, the blockbuster drug. This is true only insofar as we define blockbuster drug from within [ Read More ]