From the Guidelines
Enzalutamide is recommended for both non-metastatic and metastatic castration-resistant prostate cancer (CRPC) at a dosage of 160 mg daily, alongside continued androgen deprivation therapy (ADT). This treatment aims to delay metastasis development and prolong survival. For non-metastatic CRPC, enzalutamide is typically administered once daily, with or without food. For metastatic CRPC, the same dosage of 160 mg daily is recommended, either as a first-line treatment or following docetaxel chemotherapy, also with continued ADT.
Key Points
- The dosage of enzalutamide is 160 mg daily, which can be taken with or without food.
- Common side effects include fatigue, hot flashes, and hypertension.
- Dose reduction to 120 mg or 80 mg daily may be necessary if significant adverse effects occur.
- Regular monitoring of PSA levels, imaging studies, and clinical assessments are essential to evaluate treatment response.
- Enzalutamide works by blocking androgen receptors, preventing testosterone from binding and inhibiting nuclear translocation and DNA binding, thereby halting cancer cell growth even when testosterone levels are low.
Evidence
The recommendation is based on the most recent and highest quality study, which demonstrated the efficacy and safety of enzalutamide in patients with non-metastatic and metastatic CRPC 1. The study showed that enzalutamide improved metastasis-free survival and overall survival compared to placebo, with a median metastasis-free survival of 36.6 months versus 14.7 months (HR, 0.29; 95% CI, 0.24-0.35; P<0.001) 1. Additionally, enzalutamide has been shown to be superior to bicalutamide in terms of cancer control in metastatic CRPC, with a median time to progression of 15.7 months versus 5.8 months (HR, 0.44; 95% CI, 0.34-0.57) 1.
Administration and Monitoring
Patients should take enzalutamide at the same time each day, with or without food. Regular monitoring of PSA levels, imaging studies, and clinical assessments are essential to evaluate treatment response. Adverse events should be closely monitored, and dose reduction may be necessary if significant adverse effects occur.
Conclusion is not allowed, so the response ends here.
From the FDA Drug Label
XTANDI® is indicated for the treatment of patients with: • castration-resistant prostate cancer (CRPC) • metastatic castration-sensitive prostate cancer (mCSPC) • non‑metastatic castration‑sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR)
The recommended dosage of XTANDI is 160 mg administered orally once daily with or without food [see Clinical Pharmacology (12. 3)] until disease progression or unacceptable toxicity.
Patients with CRPC or mCSPC receiving XTANDI should also receive a gonadotropic-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.
Patients with nmCSPC with high-risk BCR may be treated with XTANDI with or without a GnRH analog.
The recommended treatment and management for non-metastatic and metastatic castration-resistant prostate cancer using Enzalutamide is:
- Dosage: 160 mg administered orally once daily with or without food
- Concomitant treatment:
- For metastatic castration-resistant prostate cancer, a gonadotropic-releasing hormone (GnRH) analog should be given concurrently or bilateral orchiectomy should have been performed
- For non-metastatic castration-resistant prostate cancer, treatment with a GnRH analog may or may not be given, depending on the clinical scenario
- Treatment duration: until disease progression or unacceptable toxicity 2 2 2
From the Research
Treatment and Management of Non-Metastatic and Metastatic Castration-Resistant Prostate Cancer using Enzalutamide
- Enzalutamide is indicated for the treatment of castration-resistant prostate cancer (CRPC) in numerous countries worldwide, with specific indications varying between individual countries 3.
- The recommended dose of enzalutamide is 160 mg once daily, which has been shown to be effective and generally well-tolerated in a broad spectrum of patients with CRPC, including those with non-metastatic and metastatic disease 3.
Efficacy in Non-Metastatic Castration-Resistant Prostate Cancer
- Enzalutamide has been shown to significantly improve metastasis-free survival among men with non-metastatic, castration-resistant prostate cancer and rapidly increasing prostate-specific antigen (PSA) levels while taking androgen-deprivation therapy 4, 5.
- In a double-blind, phase 3 trial, enzalutamide treatment led to a clinically meaningful and significant 71% lower risk of metastasis or death than placebo among men with non-metastatic, castration-resistant prostate cancer with a rapidly rising PSA level 5.
Efficacy in Metastatic Castration-Resistant Prostate Cancer
- Enzalutamide has been approved for the treatment of metastatic castration-resistant prostate cancer (CRPC) in both the post-docetaxel and chemotherapy-naïve settings 6.
- Enzalutamide plus androgen-deprivation therapy has been shown to result in longer median overall survival than placebo plus androgen-deprivation therapy among men with non-metastatic, castration-resistant prostate cancer and a rapidly rising PSA level 4.
Safety Profile
- The safety profile of enzalutamide is well-established, with adverse events of grade 3 or higher occurring in 31% of patients receiving enzalutamide, compared to 23% of those receiving placebo 5.
- The most frequently reported adverse events associated with enzalutamide are fatigue and musculoskeletal events 4.
Resistance Mechanisms
- Despite its efficacy, resistance to enzalutamide is a significant challenge, with most patients ultimately developing resistance to the treatment 7.
- Proposed mechanisms driving resistance to enzalutamide include genomic or epigenomic events that result in enhanced androgen receptor (AR) signaling, as well as alternative oncogenic pathways 7.