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Risk Factors for and Incidence of Seizures in Metastatic Castration-Resistant Prostate Cancer: A Real-World Retrospective Cohort Study

Abstract

Background and Objective

This real-world study assessed the prevalence, risk factors for, and incidence of seizures in patients with metastatic castration-resistant prostate cancer (mCRPC).

Methods

Patients with mCRPC were selected from MarketScan Commercial and Medicare Supplemental Databases between 1 January 2009 and 31 July 2012. Prevalence of seizure risk factors were described separately and in combination with other risk factors. Seizure incidence was calculated overall and for each risk factor group.

Results

The most common risk factors were history of seizure threshold-lowering medication use (35%), history of loss of consciousness (6%), history of transient ischemic attack or cerebrovascular accident (2%), treated brain metastasis (0.9%), history of seizure (0.6%), and dementia (0.5%). Overall, seizure incidence was 1.8 per 100 person-years (PYs) (95% confidence interval [CI] 1.5–2.1), being higher among patients with at least one risk factor (2.8 per 100 PYs; 95% CI 2.2–3.4) than those without risk factors (1.2 per 100 PYs; 95% CI 1.0–1.6). Seizure incidence was highest among a few patients (0.6%) with a history of seizure (82.0 per 100 PYs; 95% CI 45.9–135.2) and within this small subpopulation, higher among those with a history of anticonvulsant use (120.9 per 100 PYs; 95% CI 60.3–216.3) than without anticonvulsant use (43.5 per 100 PYs; 95% CI 11.9–111.3).

Conclusion

History of seizure is an important risk factor for seizure occurrence in patients with mCRPC, particularly in those with a history of anticonvulsant use. These findings improve understanding of the risk of seizure occurrence in patients with mCRPC, who are potential users of androgen receptor antagonists, including enzalutamide.

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Acknowledgements

The authors would like to thank Edward Faught, John Messenheimer, Roger Porter, and Howard Scher who sat on the Expert Panel of neurologists and oncologists providing guidance on the selection of important potential risk factors for seizures in the prostate cancer patient population. The authors acknowledge Noah Jamie Robinson and Michael Okobia for their valuable comments on earlier drafts of this manuscript.

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Correspondence to Charles Dharmani.

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This article does not report on any studies with human participants or animals performed by any of the authors.

Conflict of interest

Charles Dharmani is an employee of Astellas. Machaon Bonafede is an employee of Truven Health Analytics, an IBM Company, which was awarded a research contract to conduct this study with and on behalf of Astellas Pharma, Inc. Andrew Krivoshik is an employee of Astellas and holds stock in AbbVie and Abbott.

Funding

This study was funded by Astellas Pharma, Inc. and Medivation, Inc., which was acquired by Pfizer, Inc. in September 2016, the co-developers of enzalutamide. Medical writing assistance and editorial support, funded by both sponsor companies, was provided by Mei Lye and Lauren Smith from Complete HealthVizion.

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Dharmani, C., Bonafede, M. & Krivoshik, A. Risk Factors for and Incidence of Seizures in Metastatic Castration-Resistant Prostate Cancer: A Real-World Retrospective Cohort Study. Clin Drug Investig 37, 1183–1190 (2017). https://doi.org/10.1007/s40261-017-0578-0

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