The impact of patient characteristics on enzalutamide pharmacokinetics and how this relates to treatment toxicity and efficacy in metastatic prostate cancer patients.

Abstract

PURPOSE:

The aim of the study is to investigate the influence of patient characteristics, age and body mass index (BMI), on pharmacokinetics of enzalutamide, and to study the relationships between drug exposure and enzalutamide efficacy and toxicity, in mCRPC patients.

METHODS:

Data were collected in a longitudinal cohort study (ANDROPS) and a prospective observational study (ILUMINATE), both in mCRPC patients treated with enzalutamide. To investigate the influence of age and BMI on exposure, enzalutamide and N-desmethylenzalutamide levels were compared by ANOVA. To investigate the relation of exposure versus time to progression (TTP), the sum plasma levels were divided into quartiles and compared by Kaplan-Meier analysis. To assess the relation of exposure with fatigue, plasma levels in patients experiencing fatigue vs. no fatigue were compared by and independent t test.

RESULTS:

Data of 68 mCRPC patients were included for analysis. Plasma levels were not different for age or BMI. No difference in TTP between both studies was observed (383 days (95% CI 287-859), and 567 days (95% CI 351-NR), p = 0.36). Kaplan-Meier analysis of quartiles of sum levels showed no difference for TTP. Fatigue was reported by 22 patients, no difference in sum plasma levels was observed between patients with and without fatigue.

CONCLUSIONS:

We observed that age and BMI did not influence systemic exposure in patients treated with enzalutamide. No relation of exposure with efficacy or fatigue was observed. Further research using enzalutamide at a lower dose is needed to understand the relation of enzalutamide exposure and fatigue.

• Authors: Guillemette E Benoist, Inge M van Oort, David M Burger, Niven Mehra, Nielka P van Erp
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 85 Issue 4 Pg. 753-760 (04 2020) ISSN: 1432-0843 [Electronic] Germany
• PMID: 32076807 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)

Chemical References

• Benzamides
• Nitriles
• Phenylthiohydantoin
• enzalutamide

Topics

• Aged
• Benzamides
• Drug-Related Side Effects and Adverse Reactions (epidemiology, etiology)
• Follow-Up Studies
• Humans
• Longitudinal Studies
• Male
• Netherlands (epidemiology)
• Nitriles
• Phenylthiohydantoin (analogs & derivatives, pharmacokinetics, pharmacology)
• Prognosis
• Prospective Studies
• Prostatic Neoplasms, Castration-Resistant (drug therapy, pathology)
• Survival Rate
• Tissue Distribution