Enzalutamide may not increase the incidence of seizure among patients with metastatic castration-resistant prostate cancer (mCRPC) and seizure risk factors, according to a study published in JAMA Oncology.1

Previous studies showed that enzalutamide, an androgen receptor inhibitor, improves survival outcomes among men with mCRPC, but may increase the seizure rate.

For the open-label, UPWARD study (ClinicalTrials.gov Identifier: NCT01977651), researchers identified 423 patients with mCRPC and at least 1 risk factor for seizure. Risk factors included history of brain injury, use of concomitant medications that lower the seizure threshold, and history of cerebrovascular accident or transient ischemic attack.

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The median duration of enzalutamide treatment was 223 days; 76.1% of patients received treatment for at least 4 months.

Of the 366 evaluable patients, 4 had at least 1 confirmed seizure during the 4 months of enzalutamide treatment, and 3 had a seizure within 4 months following the initial 4-month treatment period.

The rate of confirmed seizures was 2.6 per 100 patient-years (7 seizures total), which compared favorably with a retrospective study that noted a seizure rate of 2.8 per 100 patient-years among patients with mCRPC and risk factors for seizure who did not receive enzalutamide.

Approximately 84% of all enrolled patients had at least 1 treatment-emergent adverse event (TEAE), and 33.3% of patients reported 1 serious TEAE. Nearly 7% of patients had at least 1 drug-related serious adverse event.

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Thirty-eight deaths occurred during or within 1 month of treatment discontinuation; investigators determined 4 deaths were drug related. None were due to seizure.

The authors concluded that “these data suggest enzalutamide did not increase seizure incidence in men with mCRPC and seizure risk factors and is an option for patients with seizure risk factors. However, it should be used with caution and input from neurology specialists.”


  1. Slovin S, Clark W, Carles J, et al. Seizure rates in enzalutamide-treated men with metastatic castration-resistant prostate cancer and risk of seizure: the UPWARD study. JAMA Oncol. 2017 Dec 7. doi: 10.1001/jamaoncol.2017.3361 [Epub ahead of print]