Trial reportTargeted oncology2023
Comparison of Cerebral Blood Flow in Regions Relevant to Cognition After Enzalutamide, Darolutamide, and Placebo in Healthy Volunteers: A Randomized Crossover Trial.
Trial report in Targeted oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03704519 (A Phase I, Randomized, Placebo-controlled, Open-label, Three Period Crossover Study to Investigate the Effect of Darolutamide and Enzalutamide on Cerebral Blood Flow in Healthy Male Volunteers.), which is not on this map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I, Randomized, Placebo-controlled, Open-label, Three Period Crossover Study to Investigate the Effect of Darolutamide and Enzalutamide on Cerebral Blood Flow in Healthy Male Volunteers.
Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Functional assessment in patients with castration-resistant prostate cancer treated with darolutamide: results from the DaroAcT study.The oncologist · 2025Trial
- Darolutamide plus androgen-deprivation therapy: propensity score matching of ARASEC and historic clinical trial patients.Future oncology (London, England) · 2025Trial
- Darolutamide in Combination With Androgen-Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer From the Phase III ARANOTE Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Trial
- Darolutamide in Japanese patients with metastatic hormone-sensitive prostate cancer: Phase 3 ARASENS subgroup analysis.Cancer medicine · 2024Trial
- Extended Safety and Tolerability of Darolutamide for Nonmetastatic Castration-Resistant Prostate Cancer and Adverse Event Time Course in ARAMIS.The oncologist · 2024Trial
- Pharmacovigilance of Androgen Receptor Pathway Inhibitors in Prostate Cancer: The Impact of Docetaxel Co-Reporting.Cancers · 2026Article
- Comparative Pharmacovigilance Analysis of Safety Signals Among Advanced Prostate Cancer Therapies Using FAERS (FDA Adverse Event Reporting System).Current oncology (Toronto, Ont.) · 2026Article
- DARolutamide ObservationaL (DAROL) study in patients with nonmetastatic castration-resistant prostate cancer: prespecified third interim analysis.Prostate cancer and prostatic diseases · 2026Observational
- [Artificial intelligence in the care of geriatric patients-more of a curse or more of a blessing?]Urologie (Heidelberg, Germany) · 2026Review
- Utilization patterns of second-generation androgen receptor pathway inhibitors as first-line therapy for prostate cancer in the United States.Prostate cancer and prostatic diseases · 2026Article
- The interplay between molecular architecture, pharmacology, and suspected adverse drug reactions associated with nonsteroidal androgen antagonists in the United Kingdom.British journal of clinical pharmacology · 2026Article
- Empirical-Null Calibration Challenges Comparative CNS Safety Signals for Androgen-Receptor Pathway Inhibitors: A FAERS Re-Analysis.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Vigilance for drug safety of darolutamide in the cancer therapies: a disproportionality analysis from the FDA Adverse Event Reporting System.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Enzalutamide effectively inhibits the growth of meningiomas via p21-dependent senescence induction.Molecular biology reports · 2026Article
- [How can the suitability of a geriatric patient for uro-oncological treatment be determined?]Urologie (Heidelberg, Germany) · 2026Review
- Integration of Darolutamide in the Treatment Landscape for Metastatic Hormone-sensitive Prostate Cancer: A Systematic Review and Network Meta-analysis of Efficacy and Safety.European urology open science · 2026Article
- The intricate interplay between circadian rhythm, androgen signaling, hormone therapy, and cellular senescence in prostate cancer.Cancer metastasis reviews · 2025Review
- Assessing the efficacy of darolutamide in metastatic hormone-sensitive prostate cancer based on subgroup meta-analysis and reconstructed individual patient data.Discover oncology · 2025Article
- Article
- Imaging characteristics of brain microstructure and cerebral perfusion in Crohn's disease patients with anxiety: A prospective comparative study.World journal of gastroenterology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOff-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.
objectiveWe 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).
methodsThis 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.
resultsDrug 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.
conclusionsDarolutamide 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. TRIAL REGISTRATION NUMBER: NCT03704519; date of registration: October 2018.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.