Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: A randomized, double-blind, placebo-controlled trial

Paul D. Brown, Stephanie Pugh, Nadia N Laack, Jeffrey S. Wefel, Deepak Khuntia, Christina Meyers, Ali Choucair, Sherry Fox, John H. Suh, David Roberge, Vivek Kavadi, Soren M. Bentzen, Minesh P. Mehta, Deborah Watkins-Bruner

Research output: Contribution to journalArticle

347 Citations (Scopus)

Abstract

BackgroundTo determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy (WBRT).MethodsAdult 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.ResultsOf 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.ConclusionsMemantine 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.

Original languageEnglish (US)
Pages (from-to)1429-1437
Number of pages9
JournalNeuro-Oncology
Volume15
Issue number10
DOIs
StatePublished - Oct 2013

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Memantine
Radiotherapy
Placebos
Brain
Cognition
Executive Function
Cognitive Dysfunction
Compliance
Confidence Intervals
Neoplasm Metastasis

Keywords

  • brain metastases
  • cognition
  • memantine
  • neuroprotective agents
  • radiotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology

Cite this

Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy : A randomized, double-blind, placebo-controlled trial. / Brown, Paul D.; Pugh, Stephanie; Laack, Nadia N; Wefel, Jeffrey S.; Khuntia, Deepak; Meyers, Christina; Choucair, Ali; Fox, Sherry; Suh, John H.; Roberge, David; Kavadi, Vivek; Bentzen, Soren M.; Mehta, Minesh P.; Watkins-Bruner, Deborah.

In: Neuro-Oncology, Vol. 15, No. 10, 10.2013, p. 1429-1437.

Research output: Contribution to journalArticle

Brown, PD, Pugh, S, Laack, NN, Wefel, JS, Khuntia, D, Meyers, C, Choucair, A, Fox, S, Suh, JH, Roberge, D, Kavadi, V, Bentzen, SM, Mehta, MP & Watkins-Bruner, D 2013, 'Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: A randomized, double-blind, placebo-controlled trial', Neuro-Oncology, vol. 15, no. 10, pp. 1429-1437. https://doi.org/10.1093/neuonc/not114
Brown, Paul D. ; Pugh, Stephanie ; Laack, Nadia N ; Wefel, Jeffrey S. ; Khuntia, Deepak ; Meyers, Christina ; Choucair, Ali ; Fox, Sherry ; Suh, John H. ; Roberge, David ; Kavadi, Vivek ; Bentzen, Soren M. ; Mehta, Minesh P. ; Watkins-Bruner, Deborah. / Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy : A randomized, double-blind, placebo-controlled trial. In: Neuro-Oncology. 2013 ; Vol. 15, No. 10. pp. 1429-1437.
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title = "Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: A randomized, double-blind, placebo-controlled trial",
abstract = "BackgroundTo determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy (WBRT).MethodsAdult 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.ResultsOf 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.ConclusionsMemantine 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.",
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T1 - Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy

T2 - A randomized, double-blind, placebo-controlled trial

AU - Brown, Paul D.

AU - Pugh, Stephanie

AU - Laack, Nadia N

AU - Wefel, Jeffrey S.

AU - Khuntia, Deepak

AU - Meyers, Christina

AU - Choucair, Ali

AU - Fox, Sherry

AU - Suh, John H.

AU - Roberge, David

AU - Kavadi, Vivek

AU - Bentzen, Soren M.

AU - Mehta, Minesh P.

AU - Watkins-Bruner, Deborah

PY - 2013/10

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N2 - BackgroundTo determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy (WBRT).MethodsAdult 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.ResultsOf 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.ConclusionsMemantine 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.

AB - BackgroundTo determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy (WBRT).MethodsAdult 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.ResultsOf 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.ConclusionsMemantine 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.

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KW - cognition

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KW - neuroprotective agents

KW - radiotherapy

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