| dc.contributor.author | Patrick, Fiona | |
| dc.date.accessioned | 2023-08-09T09:53:39Z | |
| dc.date.available | 2023-08-09T09:53:39Z | |
| dc.date.issued | 2023-05 | |
| dc.identifier.citation | Steven C. R. Williams, Ndaba Mazibuko, Owen O’Daly, Christian Zurth, Fiona Patrick, Christian Kappeler, Iris Kuss & Patricia E. Cole . Comparison of Cerebral Blood Flow in Regions Relevant to Cognition After Enzalutamide, Darolutamide, and Placebo in Healthy Volunteers: A Randomized Crossover Trial. Targ Oncol 18, 403–413 (2023). | en |
| dc.identifier.uri | https://oxfordhealth-nhs.archive.knowledgearc.net/handle/123456789/1266 | |
| dc.description | Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/. | en |
| dc.description.abstract | Off-target central nervous system (CNS) effects are associated with androgen receptor (AR)-targeting treatments for prostate cancer. Darolutamide is a structurally distinct AR inhibitor with low blood–brain barrier penetration.
Objective
We compared cerebral blood flow (CBF) in grey matter and specific regions related to cognition after darolutamide, enzalutamide, or placebo administration, using arterial spin-label magnetic resonance imaging (ASL-MRI).
Methods
This phase I, randomized, placebo-controlled, three-period crossover study administered single doses of darolutamide, enzalutamide, or placebo to 23 healthy males (aged 18–45 years) at 6-week intervals. ASL-MRI mapped CBF 4 h post-treatment. Treatments were compared using paired t-tests.
Results
Drug concentrations during scans confirmed similar unbound exposure of darolutamide and enzalutamide, with complete washout between treatments. A significant localized 5.2% (p = 0.01) and 5.9% (p < 0.001) CBF reduction in the temporo-occipital cortices was observed for enzalutamide versus placebo and versus darolutamide, respectively, with no significant differences for darolutamide versus placebo. Enzalutamide reduced CBF in all prespecified regions, with significant reductions versus placebo (3.9%, p = 0.045) and versus darolutamide (4.4%, p = 0.037) in the left and right dorsolateral prefrontal cortices, respectively. Darolutamide showed minimal changes in CBF versus placebo in cognition-relevant regions.
Conclusions
Darolutamide did not significantly alter CBF, consistent with its low blood–brain barrier penetration and low risk of CNS-related adverse events. A significant reduction in CBF was observed with enzalutamide. These results may be relevant to cognitive function with early and extended use of second-generation AR inhibitors, and warrant further investigation in patients with prostate cancer. | en |
| dc.description.uri | https://doi.org/10.1007/s11523-023-00959-5 | en |
| dc.language.iso | en | en |
| dc.subject | Brain Activity | en |
| dc.title | Comparison of Cerebral Blood Flow in Regions Relevant to Cognition After Enzalutamide, Darolutamide, and Placebo in Healthy Volunteers: A Randomized Crossover Trial | en |
| dc.type | Article | en |
| dc.contributor.discipline | Trainee Clinical Psychologist | en |
