Enzalutamide
Overview
Enzalutamide is an oral androgen receptor inhibitor used in the treatment of prostate cancer, particularly in advanced and metastatic stages. It works by blocking multiple steps in the androgen receptor signaling pathway, preventing testosterone from stimulating cancer growth. Unlike earlier hormonal therapies, enzalutamide has a stronger affinity for the androgen receptor and effectively prevents nuclear translocation and DNA binding. It is administered orally and is commonly prescribed for men with metastatic castration-resistant prostate cancer and non-metastatic castration-resistant prostate cancer. Its ability to delay disease progression and improve overall survival has made it a key therapy in modern oncology.
Background and Date of Approval
Enzalutamide was developed to overcome resistance mechanisms associated with traditional anti-androgens. The U.S. Food and Drug Administration first approved it in 2012 for metastatic castration-resistant prostate cancer after prior chemotherapy. In 2014, approval was expanded to men who had not yet received chemotherapy, reflecting strong clinical trial data showing survival benefits. In 2018, the approval extended to non-metastatic castration-resistant prostate cancer, based on studies such as the PROSPER trial, which demonstrated a significant improvement in metastasis-free survival. The European Medicines Agency and regulatory bodies in other regions also authorized its use, making it an internationally recognized therapy. Clinical evidence confirms enzalutamide’s efficacy in improving progression-free survival, delaying skeletal complications, and enhancing quality of life in prostate cancer patients.
Uses
Enzalutamide is indicated for the treatment of metastatic castration-resistant prostate cancer in men who have or have not received prior chemotherapy. It is also approved for non-metastatic castration-resistant prostate cancer in men at high risk of developing metastases. In addition, ongoing clinical research explores its role in earlier stages of prostate cancer, in combination with androgen deprivation therapy, and in metastatic hormone-sensitive prostate cancer. Its broad application across different stages of prostate cancer highlights its versatility and importance in long-term disease management.
Administration
Enzalutamide is taken orally once daily at a standard dose of 160 mg, with or without food. Tablets should be swallowed whole and taken at the same time each day. No dose modifications are generally required for mild to moderate renal impairment, but adjustments may be necessary for patients with hepatic impairment. In cases of intolerable side effects, treatment interruption or dose reduction may be required. Regular monitoring of blood pressure, liver function, and overall tolerance is recommended throughout therapy.
Side Effects
The most common side effects of enzalutamide include fatigue, hot flashes, musculoskeletal pain, headache, hypertension, dizziness, decreased appetite, constipation, diarrhea, and peripheral edema. Some patients may also experience falls, weight loss, or memory impairment. Most of these side effects are manageable with supportive care or dose modifications, and many improve with continued treatment.
Warnings
Enzalutamide may cause seizures, particularly in patients with a history of seizure disorders or other predisposing conditions. It has also been associated with posterior reversible encephalopathy syndrome, although this is rare. Other serious risks include severe hypertension, ischemic heart disease, and hepatotoxicity. Patients with cardiovascular disease require careful monitoring during treatment. Enzalutamide should not be used in women, especially those who are pregnant, due to potential harm to a developing fetus.
Precautions
Caution is advised in patients with a history of seizures, cardiovascular disease, or liver dysfunction. Enzalutamide is metabolized by CYP2C8 and CYP3A4 enzymes and may interact with drugs metabolized by these pathways. Strong CYP2C8 inhibitors can increase enzalutamide exposure and toxicity, while strong CYP3A4 inducers may reduce efficacy. Patients should avoid medications with a high risk of interaction unless supervised by a physician. Contraception is advised for male patients with partners of childbearing potential during treatment and for several months after discontinuation.
Expert Tips
Enzalutamide is best used in patients with castration-resistant disease in combination with ongoing androgen deprivation therapy. Prescribers should monitor blood pressure regularly and be alert to neurological symptoms such as seizures or cognitive decline. Pharmacists should counsel patients about taking the medicine at the same time daily, recognizing side effects like fatigue or dizziness, and reporting any neurological events promptly. Encouraging adherence is essential, as consistent daily dosing directly impacts efficacy.