title: 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.
authors: Corresponding Author: Paul D. Brown, MD, Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 97, Houston, TX 77030. pdbrown@mdanderson.org.
authors: Paul D
authors: PD
authors: Brown
authors: Stephanie
authors: S
authors: Pugh
authors: Nadia N
authors: NN
authors: Laack
authors: Jeffrey S
authors: JS
authors: Wefel
authors: Deepak
authors: D
authors: Khuntia
authors: Christina
authors: C
authors: Meyers
authors: Ali
authors: A
authors: Choucair
authors: Sherry
authors: S
authors: Fox
authors: John H
authors: JH
authors: Suh
authors: David
authors: D
authors: Roberge
authors: Vivek
authors: V
authors: Kavadi
authors: Soren M
authors: SM
authors: Bentzen
authors: Minesh P
authors: MP
authors: Mehta
authors: Deborah
authors: D
authors: Watkins-Bruner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000532:radiotherapy*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D016371:Cranial Irradiation / Q000009:adverse effects*; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D008875:Middle Aged; D009367:Neoplasm Staging; D009483:Neuropsychological Tests; D011379:Prognosis; D015996:Survival Rate
chemical_list: D018691:Excitatory Amino Acid Antagonists; D008559:Memantine
keywords: brain metastases; cognition; memantine; neuroprotective agents; radiotherapy
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