Therapeutic role of memantine for the prevention of cognitive decline in cancer patients with brain metastasis receiving whole-brain radiotherapy: a narrative review

Folloso, Melmar Cerilo; Torres, Mazelle; Ciocon, Stephen Lowell; Ong, Jed Noel; Flores, Jerickson Abbie; Catindig, Joseree-Ann

doi:10.1590/1980-5764-DN-2021-0102

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Dementia & Neuropsychologia

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Articles • Dement. neuropsychol. 16 (3) • jul-sep 2022 • https://doi.org/10.1590/1980-5764-DN-2021-0102 copy

Therapeutic role of memantine for the prevention of cognitive decline in cancer patients with brain metastasis receiving whole-brain radiotherapy: a narrative review

PAPEL TERAPÊUTICO DA MEMANTINA NA PREVENÇÃO DO DECLÍNIO COGNITIVO EM PACIENTES COM CÂNCER COM METÁSTASE CEREBRAL RECEBENDO RADIOTERAPIA CEREBRAL TOTAL: UMA REVISÃO NARRATIVA

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT.

Brain metastases are the most common central nervous system tumors. The mainstay treatment for this tumor in low to middle income countries is whole brain radiation therapy. Irreversible cognitive decline is associated with the use of whole brain radiotherapy. Several pharmacologic and nonpharmacologic options have been employed in studies focusing on the prevention of cognitive decline following whole-brain radiation therapy. Memantine use has been shown to provide some benefit in reducing the rate of decline in cognitive function and time to cognitive failure. The objective of this review article is to provide a summary on available primary literature on the therapeutic role of memantine for the prevention of cognitive decline in cancer patients with brain metastasis receiving whole brain radiotherapy.

Keywords:
Memantine; Radiotherapy; Brain neoplasms; Cognition

Author (year)	Study design	Level of evidence	n¹	Inclusion criteria	Study arms	Outcome	Result of outcome
Brown et al. (2013)²⁶26. Brown PD, Pugh S, Laack NN, Wefel JS, Khuntia D, Meyers C, et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro Oncol. 2013;15(10):1429-37. https://doi.org/10.1093/neuonc/not114 https://doi.org/https://doi.org/10.1093/...	Randomized double-blind, placebo-controlled trial	1	554	Adult patients with brain metastases receiving WBRT²	WBRT+memantine WBRT+placebo	HVLT-R for Delayed Recall at 24 weeks	No significant difference in delayed recall (primary outcome) between the two arms p=0.059)
Brown et al. (2020)²⁸28. Brown PD, Gondi V, Pugh S, Tome WA, Wefel JS, Armstrong TS, et al. Hippocampal avoidance during whole-brain radiotherapy plus memantine for patients with brain metastases: phase III trial NRG oncology CC001. J Clin Oncol. 2020;38(10):1019-29. https://doi.org/10.1200/JCO.19 https://doi.org/https://doi.org/10.1200/...	Randomized parallel, open-label controlled trial	1	518	Adult patients with brain metastases outside a 5-mm margin around either hippocampus receiving WBRT	WBRT+memantine HA-WBRT⁴+memantine	Time to cognitive function failure	Significant reduction in cognitive failure in patients under HA-WBRT plus memantine (adjusted hazard ratio, 0.74; 95%CI 0.58-0.95; p=0.02).
Wong et al. (2016)²⁷27. Wong P, Leppert IR, Roberge D, Boudam K, Brown PD, Muanza T, et al. A pilot study using dynamic contrast enhanced-MRI as a response biomarker of the radioprotective effect of memantine in patients receiving whole brain radiotherapy. Oncotarget. 2016;7(32):50986-96. https://doi.org/10.18632/oncotarget.9653 https://doi.org/https://doi.org/10.18632...	Randomized parallel, open-label placebo-controlled trial	1	14	Adult patients with brain metastases receiving WBRT (12 from RTOG 0614)	WBRT+placebo WBRT+Memantine*	DCE-MRI measures of tumor tissue and normal-appearing white matter (NAWM) vascular permeability	significantly (p=0.01) reduced normal-appearing vascular permeability changes following radiotherapy
Laack et al. (2018)²⁵25. Laack NN, Pugh SL, Brown PD, Fox S, Wefel JS, Meyers C, et al. The association of health-related quality of life and cognitive function in patients receiving memantine for the prevention of cognitive dysfunction during whole-brain radiotherapy. Neurooncol Pract. 2019;6(4):274-82. https://doi.org/10.1093/nop/npy038 https://doi.org/https://doi.org/10.1093/...	Randomized parallel, open-label controlled trial	1	442	Adult patients with brain metastases receiving WBRT (from RTOG 0614)	WBRT+memantine WBRT+placebo	Association of health-related quality of life and cognitive function	Baseline cognitive function correlated significantly with Medical Outcomes Scale-Cognitive Functioning Scale (MOS-C).

Academia Brasileira de Neurologia, Departamento de Neurologia Cognitiva e Envelhecimento R. Vergueiro, 1353 sl.1404 - Ed. Top Towers Offices, Torre Norte, São Paulo, SP, Brazil, CEP 04101-000, Tel.: +55 11 5084-9463 | +55 11 5083-3876 - São Paulo - SP - Brazil
E-mail: revistadementia@abneuro.org.br | demneuropsy@uol.com.br

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[1] Correspondence: Melmar Cerilo Folloso; Email: melmar.folloso@gmail.com.