A Prospective Randomised Trial to Determine the Effect of a Reduced Versus Standard Dose of Enzalutamide on Side Effects in Frail Patients with Prostate Cancer

Emmy Boerrigter; Joanneke K Overbeek; Guillemette E Benoist; Diederik M Somford; Paul Hamberg; Jolien Tol; Brian Scholtes; Annelieke E C A B Willemsen; Laurien M Buffart; Roy P C Kessels; Niven Mehra; Inge M van Oort; Nielka P van Erp

doi:10.1016/j.euo.2024.02.009

A Prospective Randomised Trial to Determine the Effect of a Reduced Versus Standard Dose of Enzalutamide on Side Effects in Frail Patients with Prostate Cancer

Eur Urol Oncol. 2024 Mar 13:S2588-9311(24)00057-9. doi: 10.1016/j.euo.2024.02.009. Online ahead of print.

Affiliations

¹ Department of Pharmacy, Radboudumc Research Institute for Medical Innovation, Nijmegen, The Netherlands.
² Department of Clinical Pharmacy and Pharmacology, Deventer Hospital, Deventer, The Netherlands.
³ Department of Urology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
⁴ Department of Medical Oncology, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands.
⁵ Department of Medical Oncology, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands.
⁶ Department of Medical Oncology, Maasziekenhuis Pantein, Beugen, The Netherlands.
⁷ Department of Internal Medicine, Tergooi Medical Center, Hilversum, The Netherlands.
⁸ Department of Medical BioSciences, Radboudumc Research Institute for Medical Innovation, Nijmegen, The Netherlands.
⁹ Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands; Department of Medical Psychology and Radboudumc Alzheimer Center, Radboudumc, Nijmegen, The Netherlands; Vincent van Gogh Institute for Psychiatry, Venray, The Netherlands.
¹⁰ Department of Medical Oncology, Radboudumc Research Institute for Medical Innovation, Nijmegen, The Netherlands.
¹¹ Department of Urology, Radboudumc Research Institute for Medical Innovation, Nijmegen, The Netherlands.
¹² Department of Pharmacy, Radboudumc Research Institute for Medical Innovation, Nijmegen, The Netherlands. Electronic address: Nielka.vanErp@radboudumc.nl.

PMID: 38485614
DOI: 10.1016/j.euo.2024.02.009

Abstract

Background and objective: Enzalutamide is a potent androgen receptor signalling inhibitor, effectively used for the treatment of different stages of prostate cancer. Side effects occur frequently at the registered dose, whilst a lower dose might be equally effective. Therefore, the aim of this study is to determine the effect of a reduced dose of enzalutamide on side effects in frail patients with prostate cancer.

Methods: This multicentre randomised trial compared the standard enzalutamide dose of 160 mg once daily (OD) with a reduced dose of 120 mg OD in frail patients with prostate cancer. Fatigue, cognitive side effects, and depressive symptoms were measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaire, Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) questionnaire, and Geriatric Depression Scale-15 (GDS-15). Linear mixed-effect models were used to study differences in side effects over time between both groups.

Key findings and limitations: In total, 52 patients were included in the analysis (25 reduced dose and 27 standard dose). Patients treated with the reduced dose had significantly lower fatigue after 24 wk than those with the standard dose (difference FACIT-Fatigue 6.2; 95% confidence interval 1.4-11.0; p = 0.01). Patients treated with the reduced dose showed stable fatigue, cognitive side effects, and depressive symptoms over time, whilst patients with the standard dose showed significantly worse side effects after 24 wk than at baseline.

Conclusions and clinical implications: A reduced dose of enzalutamide results in less fatigue, cognitive side effects, and depressive symptoms in frail patients with prostate cancer than the standard dose, without any indication of interference with efficacy endpoints.

Patient summary: In this report, we looked at the side effects of enzalutamide at two dose levels. We found that, in frail patients, three tablets a day result in less fatigue than four tablets a day. Patients treated with four tablets a day showed an increase in fatigue, cognitive side effects, and depression. We conclude that a lower dose of three tablets can be used to alleviate side effects without indications for less efficacy.

Keywords: Dose; Enzalutamide; Frail patients; Prostate cancer; Side effects.