Enzalutamide
Enzalutamide is a second-generation androgen-receptor antagonist for prostate cancer. Unlike older agents it also blocks receptor nuclear translocation and DNA binding, giving stronger androgen-signalling inhibition. It improves survival in castration-resistant disease but carries seizure risk and fatigue.
01 Overview
Marketed as Xtandi, enzalutamide is a mainstay of castration-resistant and metastatic hormone-sensitive prostate cancer, backed by large randomised trials showing survival benefit. It is far more potent than first-generation antagonists.
Its principal safety concerns are a small increased seizure risk (it crosses the blood-brain barrier and affects GABA signalling), fatigue, hypertension, and falls in older patients.
02 Mechanism
Binds the androgen receptor with high affinity and blocks androgen binding, receptor nuclear translocation, and DNA binding, producing more complete inhibition of androgen signalling than earlier antagonists.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Prostate cancer | 160 mg/day | Oral | 160 mg once daily |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Improved survival in prostate cancerProlongs overall and progression-free survival in castration-resistant disease. | Survival benefit in RCTs | Clinical | |
| Potent androgen-signalling blockadeMore complete AR inhibition than first-generation antagonists. | Strong | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| SeizuresSmall dose-related increase in seizure risk. | Severe | Rare | Clinical | |
| Fatigue and fallsTiredness, asthenia, and increased fall risk, notably in older men. | Moderate | Very common | Clinical | |
| HypertensionElevated blood pressure during treatment. | Moderate | Common | Clinical |