Neuro-oncology 2013-10
Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial.
Abstract
Background
To determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy (WBRT).
Methods
Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine (20 mg/d), within 3 days of initiating radiotherapy for 24 weeks. Serial standardized tests of cognitive function were performed.
Results
Of 554 patients who were accrued, 508 were eligible. Grade 3 or 4 toxicities and study compliance were similar in the 2 arms. There was less decline in delayed recall in the memantine arm at 24 weeks (P = .059), but the difference was not statistically significant, possibly because there were only 149 analyzable patients at 24 weeks, resulting in only 35% statistical power. The memantine arm had significantly longer time to cognitive decline (hazard ratio 0.78, 95% confidence interval 0.62-0.99, P = .01); the probability of cognitive function failure at 24 weeks was 53.8% in the memantine arm and 64.9% in the placebo arm. Superior results were seen in the memantine arm for executive function at 8 (P = .008) and 16 weeks (P = .0041) and for processing speed (P = .0137) and delayed recognition (P = .0149) at 24 weeks.
Conclusions
Memantine was well tolerated and had a toxicity profile very similar to placebo. Although there was less decline in the primary endpoint of delayed recall at 24 weeks, this lacked statistical significance possibly due to significant patient loss. Overall, patients treated with memantine had better cognitive function over time; specifically, memantine delayed time to cognitive decline and reduced the rate of decline in memory, executive function, and processing speed in patients receiving WBRT. RTOG 0614, ClinicalTrials.gov number CT00566852.
Related Questions
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Aizer et al., JCO 2025 - A multi-instituitional Brigham Dana-Farber-led trial randomized 196 patients with 5-20 brain metastases to stereotactic radiosurgery (SRS) or hippocampal avoidance whole brain radiotherapy (HA-WBRT). Patients treated on the SRS arm had significantly less symptom burden, wit...
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The study by Brown et al., PMID 23956241 showing the benefit to memantine in terms of delay/decrease in neurocognitive function was in patients receiving whole brain radiation therapy. That is why I routinely offer memantine to patients receiving WBRT. (Even with the study results, I almost always h...
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I do not as there is currently no evidence to support this. There was a trial conducted by the RTOG for whole brain RT patients with mets which demonstrated a trend towards improvement in time to cognitive decline (53.8 % at 24 weeks for memantine vs 64.9 % for placebo), executive function at 8 and ...
What is the rate of dementia following whole brain radiotherapy in patients with brain metastases who survive for over a year?
To answer this question we need to have a common understanding of "dementia." I think that those of us who follow patients long-term after WBRT all agree that there are cognitive changes that develop. From the placebo arm of RTOG 0614 we know that at 6 months 65% of patients experienced cognitive dy...
Do you use either memantine or hippocampal sparing technique to preserve cognitive function when giving whole brain radiotherapy?
Dr. @Dr. First Last and I put together the response below:We use memantine and hippocampal sparing technique for all brain metastasis patients who are planning to receive WBRT. This is based off the recently published phase III trial NRG CC001 that found hippocampal avoidance WBRT plus memantine res...