Central Nervous System Toxicity in Prostate Cancer Patients Treated with Androgen Receptor Signaling Inhibitors: A Systematic Review, Meta-analysis, and Network Meta-analysis
Language English Country United States Media print-electronic
Document type Journal Article, Systematic Review, Meta-Analysis, Review
PubMed
39571519
DOI
10.1016/j.clgc.2024.102251
PII: S1558-7673(24)00221-0
Knihovny.cz E-resources
- Keywords
- ARSI, Central Nervous System, Meta-analysis, Network Meta-analysis, Prostate Cancer,
- MeSH
- Androgen Receptor Antagonists * adverse effects administration & dosage therapeutic use MeSH
- Benzamides MeSH
- Phenylthiohydantoin adverse effects administration & dosage MeSH
- Humans MeSH
- Prostatic Neoplasms * drug therapy pathology MeSH
- Central Nervous System Diseases chemically induced MeSH
- Nitriles MeSH
- Pyrazoles MeSH
- Randomized Controlled Trials as Topic MeSH
- Network Meta-Analysis as Topic * MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
- Review MeSH
- Systematic Review MeSH
- Names of Substances
- Androgen Receptor Antagonists * MeSH
- Benzamides MeSH
- darolutamide MeSH Browser
- enzalutamide MeSH Browser
- Phenylthiohydantoin MeSH
- Nitriles MeSH
- Pyrazoles MeSH
BACKGROUND: Androgen-receptor signaling inhibitors (ARSIs) significantly improve survival in systemic therapy for advanced/metastatic prostate cancer (PCa) patients; however possible central nervous system (CNS) toxicity is an unaddressed concern. We aimed to assess and compare the incidence of CNS-related adverse events (AEs) secondary to the treatment of PCa patients with different ARSIs. MATERIALS: In August 2023, a comprehensive seach was conducted in three databases for randomized controlled trials (RCTs) of PCa patients receiving ARSIs plus ADT. The primary endpoints included mental impairment, cognitive impairment, seizure, fatigue, and falls. RESULTS: Twenty-six RCTs, comprising 20,328 patients, were included in meta-analyses and network meta-analyses (NMAs). ARSIs increased the risk of mental impairment (RR: 1.72; 95% CI, 1.09-2.71), cognitive impairment (RR: 2.25; 95% CI, 1.78-2.86), seizure (RR: 2.20, 95% CI, 1.09-4.45), fatigue (RR: 1.31, 95% CI, 1.20-1.43), and falls (RR: 2.07, 95% CI, 1.60-2.67) compared to standard of care (SOC). Based on NMAs, Enzalutamide showed a significant increase in risk for all assessed CNS-related AEs, while Abiraterone demonstrated significant risk increases in cognitive impairment, fatigue, and falls. Conversely, Darolutamide did not exhibit significant increases in risk for any CNS-related AEs, except for fatigue. CONCLUSIONS: The addition of ARSIs to ADT increased all examined CNS-related AEs compared to SOC. Each ARSI is associated with a distinct profile of CNS-related AEs. Careful patient selection and monitoring for CNS sequelae is necessary to achieve the best quality of life in patients on ARSI + ADT for PCa.
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