Donepezil for Irradiated Brain Tumor Survivors: A Phase III Randomized Placebo-Controlled Clinical Trial

Rapp, Stéphen R.; Case, L. D.; Peiffer, Ann M.; Naughton, Michelle M.; Chan, Michael D.; Stieber, Volker W.; Moore, Dennis F.; Falchuk, Steven C.; Piephoff, James; Edenfield, William J.; Giguere, Jeffrey K.; Loghin, Monica; Shaw, Edward G.

doi:10.1200/jco.2014.58.4508

Cited by 209 publications

(158 citation statements)

References 27 publications

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“…The adult brain has historically been considered relatively refractory to WBRT, which is administered to roughly 200,000 cancer patients per year. 71 Increasing recognition of the cognitive toll incurred by adults following WBRT is now prompting critical reevaluation of the role of WBRT in adults with brain metastases. 7 At the other extreme, stereotactic radiosurgery (SRS) minimizes off-target radiation exposure, serving as an adjunct to or alternative for discrete resections.…”

Section: Multiple Paths To Radiation-induced Brain Injurymentioning

confidence: 99%

Radiation-induced brain injury: low-hanging fruit for neuroregeneration

Burns

Awad

et al. 2016

FOC

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Brain radiation is a fundamental tool in neurooncology to improve local tumor control, but it leads to profound and progressive impairments in cognitive function. Increased attention to quality of life in neurooncology has accelerated efforts to understand and ameliorate radiation-induced cognitive sequelae. Such progress has coincided with a new understanding of the role of CNS progenitor cell populations in normal cognition and in their potential utility for the treatment of neurological diseases. The irradiated brain exhibits a host of biochemical and cellular derangements, including loss of endogenous neurogenesis, demyelination, and ablation of endogenous oligodendrocyte progenitor cells. These changes, in combination with a state of chronic neuroinflammation, underlie impairments in memory, attention, executive function, and acquisition of motor and language skills. Animal models of radiation-induced brain injury have demonstrated a robust capacity of both neural stem cells and oligodendrocyte progenitor cells to restore cognitive function after brain irradiation, likely through a combination of cell replacement and trophic effects. Oligodendrocyte progenitor cells exhibit a remarkable capacity to migrate, integrate, and functionally remyelinate damaged white matter tracts in a variety of preclinical models. The authors here critically address the opportunities and challenges in translating regenerative cell therapies from rodents to humans. Although valiant attempts to translate neuroprotective therapies in recent decades have almost uniformly failed, the authors make the case that harnessing human radiation-induced brain injury as a scientific tool represents a unique opportunity to both successfully translate a neuroregenerative therapy and to acquire tools to facilitate future restorative therapies for human traumatic and degenerative diseases of the central nervous system.

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Section: Multiple Paths To Radiation-induced Brain Injurymentioning

confidence: 99%

Radiation-induced brain injury: low-hanging fruit for neuroregeneration

Burns

Awad

et al. 2016

FOC

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“…However, significant differences favoring donepezil were observed for memory, motor speed and dexterity. Not unexpectedly, the benefit of donepezil was found to be greater in those patients who were more cognitively impaired at baseline 47 .…”

Section: Treatment and Mitigationmentioning

confidence: 89%

Radiation Toxicity in the Central Nervous System: Mechanisms and Strategies for Injury Reduction

Smart

2017

Seminars in Radiation Oncology

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The potential for radiation-induced toxicities in the brain produce significant anxiety, both among patients receiving radiation therapy and those radiation oncologists providing treatment. These concerns often play a significant role in the medical decision making process for most patients with diseases in which radiotherapy may be a treatment consideration1. While the precise mechanisms of neurotoxicity and neurodegeneration following ionizing radiation exposure continue to be poorly understood from a biological perspective, there is an increasing body of scientific and clinical literature that is producing a better understanding of how radiation causes brain injury, factors which determine whether toxicities occur, and potential preventative, treatment and mitigation strategies for patients at high risk or with symptoms of injury. This review will focus primarily on injuries and biological processes described in mature brain.

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“…Two effective remedies were memantine (26,27) and donepezil (28,29). Both are drugs to treat Alzheimer's disease and both have different targets of action (30).…”

Section: Similarity and Relationship To Forms Of Senile Dementia Inclmentioning

confidence: 99%

A link between vascular damage and cognitive deficits after whole-brain radiation therapy for cancer: A clue to other types of dementia?

Yamada

2016

DD&T

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Donepezil for Irradiated Brain Tumor Survivors: A Phase III Randomized Placebo-Controlled Clinical Trial

Cited by 209 publications

References 27 publications

Radiation-induced brain injury: low-hanging fruit for neuroregeneration

Radiation-induced brain injury: low-hanging fruit for neuroregeneration

Radiation Toxicity in the Central Nervous System: Mechanisms and Strategies for Injury Reduction

A link between vascular damage and cognitive deficits after whole-brain radiation therapy for cancer: A clue to other types of dementia?

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