Enzalutamide is an orally administered androgen-receptor signaling inhibitor used in specified prostate cancer treatment settings.
Its clinical role is based on the importance of androgen-receptor signaling in prostate cancer. Although androgen deprivation reduces circulating testosterone, prostate-cancer cells can continue to depend on androgen-receptor signaling. Enzalutamide directly interferes with that signaling pathway.
The European Medicines Agency describes Xtandi, containing enzalutamide, for several prostate-cancer settings, including high-risk biochemical recurrent non-metastatic hormone-sensitive prostate cancer, metastatic hormone-sensitive prostate cancer and castration-resistant prostate cancer.
Pharmacological Class
Enzalutamide is an androgen-receptor inhibitor.
The androgen receptor is a steroid hormone receptor that functions as a transcriptional regulator. When activated by androgen hormones, it can enter the nucleus and influence the expression of genes involved in cellular growth and survival.
Enzalutamide interferes with this process.
Mechanism of Action
The medicine has several effects on androgen-receptor signaling.
Enzalutamide:
- Competes with androgens for the androgen receptor.
- Reduces androgen-receptor activation.
- Interferes with movement of the receptor into the cell nucleus.
- Reduces recruitment of androgen-receptor signaling machinery to DNA.
Together, these effects reduce androgen-receptor-driven gene transcription.
The result is suppression of an important growth pathway in prostate cancer.
Clinical Role in Hormone-Sensitive Disease
Hormone-sensitive prostate cancer remains responsive to treatments that suppress or block androgen signaling.
For metastatic hormone-sensitive prostate cancer, current EMA information describes enzalutamide in combination with androgen-deprivation therapy.
In selected high-risk biochemical recurrent non-metastatic hormone-sensitive prostate cancer, enzalutamide may have a role in patients who are unsuitable for salvage radiotherapy, according to the applicable product information.
Clinical Role in Castration-Resistant Disease
Castration-resistant prostate cancer has progressed despite androgen-deprivation therapy and low testosterone levels.
The term does not mean that the androgen receptor is no longer involved. Prostate-cancer cells may maintain androgen-receptor activity through multiple biological adaptations.
By directly inhibiting androgen-receptor signaling, enzalutamide addresses a pathway that may remain important after conventional androgen deprivation.
Administration
Current European product information describes oral administration once daily. The reference product’s recommended adult dose is 160 mg once daily.
The supplied product for this website is Enzamide 40 mg. A 40 mg dosage unit should not be confused with the total prescribed daily dose.
Patients should use the dose specifically prescribed for them.
Pharmacokinetic Considerations
Enzalutamide is absorbed after oral administration and undergoes metabolism to active and inactive metabolites.
The active metabolite contributes to the overall pharmacological effect.
The medicine has a relatively long elimination half-life, supporting once-daily administration.
Because enzalutamide can influence drug-metabolizing enzymes, its interaction profile is clinically important.
Drug Interactions
Enzalutamide can induce several metabolic enzymes and transport systems. As a result, it may reduce exposure to medicines that depend on those pathways.
This means the patient’s medication list should be reviewed before treatment.
Important information to provide to a healthcare professional includes:
- Prescription medicines
- Over-the-counter medicines
- Anticoagulants
- Antiepileptic medicines
- Cardiovascular medicines
- Diabetes medicines
- Herbal preparations
- Vitamins and supplements
A medication should not be stopped simply because an interaction is suspected. The prescribing clinician or pharmacist should determine the appropriate management.
Neurological Considerations
Seizures are an important safety consideration with enzalutamide.
Patients with previous seizure disorders or other conditions that may lower the seizure threshold should inform their healthcare professional before treatment.
Other neurological or predisposing factors should also be considered.
Cardiovascular Considerations
Ischemic heart disease is another important clinical consideration identified in European product information.
Patients with cardiovascular disease should discuss their medical history before starting treatment.
Blood pressure and cardiovascular symptoms may require clinical attention during therapy.
Falls and Fractures
Prostate-cancer patients may already have an increased risk of falls or fractures because of age, disease, hormonal treatment or bone involvement.
Enzalutamide treatment has been associated with falls and fractures, making assessment of overall fall and bone health relevant.
Monitoring
Monitoring depends on the patient’s condition and treatment plan.
Healthcare professionals may monitor:
- Prostate-specific antigen
- Disease symptoms
- Treatment response
- Blood pressure
- Cardiovascular status
- Neurological symptoms
- Fall risk
- Bone health
- Concomitant medications
- Adverse reactions
Monitoring does not necessarily mean that every test is required for every patient.
Clinical Evidence
Enzalutamide’s clinical development has included large randomized studies evaluating its use in different prostate-cancer populations.
Results from clinical trials support its role in selected treatment settings, but clinical-trial outcomes should not be interpreted as guarantees for individual patients.
The relevance of evidence depends on:
- Disease stage
- Prior treatment
- Patient characteristics
- Study population
- Comparator
- Treatment combination
- Regulatory indication
Clinical Decision-Making
The choice of enzalutamide is part of a broader prostate-cancer treatment strategy.
A specialist may consider alternative or additional approaches, including:
- Androgen-deprivation therapy
- Other androgen-receptor pathway inhibitors
- Chemotherapy
- Radiotherapy
- Surgery
- Radiopharmaceutical treatment
- Targeted therapies
- Other systemic treatments
The appropriate approach depends on the patient’s specific disease.
Enzalutamide is a targeted hormonal therapy that blocks androgen-receptor signaling. Its clinical role extends across selected hormone-sensitive and castration-resistant prostate-cancer settings.
Because of its pharmacological activity and interaction profile, treatment requires appropriate medical supervision.