Initial dose reduction of enzalutamide does not decrease the incidence of adverse events in castration-resistant prostate cancer

Abstract

Background There was no clear evidence whether the initial dose of enzalutamide affects the incidence of adverse events (AEs), and oncological outcome in patients with castration-resistant prostate cancer (CRPC). Methods The clinical charts of 233 patients with CRPC treated with enzalutamide were reviewed retrospectively. After 1:3 propensity score matching (PSM), 124 patients were divided into a reduced dose group and a standard dose group, and the prostate specific antigen (PSA) response and the incidence of AEs were compared. Results 190 patients with CRPC initiated with standard dose enzalutamide were younger and better performance status compared with 43 patients beginning with reduced dose. After PSM, the baseline characteristics were not different between the standard and the reduced dose group. In the PSM cohort, the PSA response rate was significantly lower in the reduced dose group than in the standard dose group (-66.3% and -87.4%, p = 0.02). The incidence rates of AEs were not statistically different between the groups (22.6% and 34.4%, respectively, p = 0.24). Conclusion Initiating treatment with a reduced dose of enzalutamide did not significantly decrease the incidence rate of AEs, and it showed poorer PSA response rate. There is no clear rationale for treating with a reduced initial dose of enzalutamide to reduce the incidence of AEs.

Pharmacist-Urologist Collaborative Management Improves Clinical Outcomes in Patients With Castration-Resistant Prostate Cancer Receiving Enzalutamide

“…Other factors, such as higher PSA at the start of enzalutamide, shorter duration of ADT before CRPC, and previous treatments were significantly associated with the time to enzalutamide discontinuation. These results are consistent with those of previous studies ( Emamekhoo et al, 2018 ; Terada et al, 2016 ; Tsuzuki et al, 2021 ; Yokomizo et al, 2022).…”

“…Gastrointestinal toxicities including constipation (30 suggestions) and anorexia (16 suggestions) were the most frequent suggestions among supportive care. Pharmacists have suggested dose adjustment of enzalutamide based on the severity of fatigue, because some studies suggest this as a potential approach to managing this symptom ( Terada et al, 2016 ; Vinh-Hung et al, 2020 ; Miura et al, 2021 ; Tsuzuki et al, 2021 ). The various interventions by pharmacists seemed to contribute to prolonging the time to enzalutamide discontinuation and time to PSA progression.…”

“…If we analyze data which including the patients who started enzalutamide at 160 mg/day, the time to enzalutamide discontinuation and time to PSA progression were still significantly prolonged in the collaborative management group (data not shown). Several studies have reported that this factor had no effect on the time to enzalutamide discontinuation or PSA progression ( Terada et al, 2016 ; Vinh-Hung et al, 2020 ; Miura et al, 2021 ; Tsuzuki et al, 2021 ). On contrary, one retrospective study suggested inferior oncological outcomes when treated with reduced-dose androgen receptor pathway inhibitors for CRPC ( Yamada et al, 2022 ).…”

“…Before January 2015, all patients received enzalutamide at 160 mg/day, and the dose was modified according to each patient’s condition. Thereafter, most patients started enzalutamide at 80–120 mg/day (initial dose reduction), and the dose was escalated to 120 and 160 mg sequentially while confirming tolerability ( Vinh-Hung et al, 2020 ; Miura et al, 2021 ; Tsuzuki et al, 2021 ). Thus, we excluded 16 patients who were started enzalutamide at 160 mg/day in this study.…”

Functional impact of androgen‐targeted therapy on patients with castration‐resistant prostate cancer

“… 50 Some methods of improving tolerability by modifying the dose, such as starting at a low dose or, in the case of abiraterone acetate, taking treatment with food, have also been tried. 51 , 52 , 53 , 54 , 55 , 56 , 57 These approaches, however, alter drug exposure and, particularly in the case of a food effect on abiraterone exposure, the impact on treatment effectiveness and safety is inconsistent; as a result, the prescribing information for abiraterone acetate mandates against taking the drug with food. 58 , 59 The need for dose reduction may be higher in patients receiving enzalutamide than in those receiving abiraterone acetate.…”