Safety evaluation of enzalutamide dose-escalation strategy in patients with castration-resistant prostate cancer

Enzalutamide (ENZ) is an androgen receptor inhibitor used for the treatment of castration-resistant prostate cancer (CRPC). The aim of this study was to evaluate the safety of the ENZ by dose-escalation strategy in patients with CRPC.

We retrospectively reviewed patients with CRPC who received standard ENZ (started at 160 mg) or dose-escalation ENZ (started at 80 mg followed by dose escalation) from May 2014 to June 2019 in our hospital. Safety and time to treatment failure (TTF) were evaluated. Multivariate logistic regression analysis was used to evaluate adverse events and drug discontinuation. Multivariate Cox regression analysis was used to evaluate TTF.

Among 107 patients, 17 patients received standard ENZ and 90 patients received dose-escalation ENZ therapy. Adverse events (any grade) were observed in 88.2% of patients in the standard group and 63.3% in the dose-escalation group (P = 0.020). Grade ≥3 adverse events were observed in 23.5% and 6.7% of the patients in the standard and dose-escalation groups, respectively, (P = 0.021). Discontinuation due to adverse events was 35.3% and 12.2% in the standard and dose-escalation groups, respectively (P = 0.070). Median TTF was 10.4 months (95% confidential interval [CI]: 2.6-31.3 months) and 18.0 months (95% CI: 11.5-22.8 months) in the standard and dose-escalation groups, respectively (Hazard ratio: 0.60, 95% CI: 0.29-1.30, P = 0.194).

With the ENZ dose-escalation strategy, adverse events related to ENZ of any grade and grade ≥3 were significantly decreased, and discontinuation due to adverse events also decreased. Therefore, the dose-escalation strategy could be useful in optimizing the dose of ENZ.