Enzalutamide for Prostate Cancer (Xtandi)

Enzalutamide, marketed as

Xtandi

, is an androgen receptor inhibitor used primarily to treat advanced prostate cancer. It blocks testosterone and other androgens from binding to cancer cells, slowing their growth and spread.

About enzalutamide

Enzalutamide is a targeted hormone therapy for men with prostate cancer that has progressed despite other treatments. It is effective for castration-resistant prostate cancer (CRPC), where tumors grow despite low testosterone levels, and metastatic castration-sensitive prostate cancer (mCSPC). The drug is taken orally as capsules and has shown benefits in extending survival, delaying metastasis, and improving quality of life in clinical trials.

Developed by Astellas Pharma and Pfizer, enzalutamide was first approved by the FDA in 2012 for metastatic CRPC post-chemotherapy. Subsequent approvals expanded its use to earlier stages, including non-metastatic CRPC and high-risk biochemical recurrence in non-metastatic hormone-sensitive prostate cancer (nmHSPC).

Key facts about enzalutamide

• Drug group: Androgen receptor inhibitor (nonsteroidal antiandrogen).
• Brand name: Xtandi.
• Used for: Prostate cancer at various advanced stages.
• Dose: Typically 160 mg once daily.
• Available as: 40 mg and 80 mg capsules.

About prostate cancer

Prostate cancer develops in the prostate gland and relies on male hormones like testosterone for growth. Early-stage cancers may be managed with surgery, radiation, or active surveillance. Advanced cases, including metastatic disease, often require hormone therapies like enzalutamide to suppress androgen signaling.

Hormone-sensitive prostate cancer responds to androgen deprivation therapy (ADT), such as leuprolide. However, many cases become castration-resistant, continuing to grow despite low testosterone. Enzalutamide addresses this by directly inhibiting androgen receptors on cancer cells.

How enzalutamide works

Enzalutamide competitively binds to the androgen receptor, preventing testosterone and dihydrotestosterone from activating it. This inhibits nuclear translocation of the receptor, DNA binding, and co-activator recruitment, ultimately halting prostate cancer cell proliferation and inducing apoptosis.

In clinical settings, it extends metastasis-free survival, particularly in high-risk patients with rising PSA post-local therapy. For instance, the EMBARK trial demonstrated superior outcomes with enzalutamide plus leuprolide versus leuprolide alone in non-metastatic castration-sensitive cancer with biochemical recurrence.

How and when to take or use enzalutamide

Dosage

The standard dose is

160 mg (four 40 mg capsules) taken once daily

, at the same time each day. It can be taken with or without food. Swallow capsules whole with water; do not chew, dissolve, or open them.

Duration

Treatment continues until disease progression or unacceptable toxicity. In some protocols, like EMBARK, treatment pauses if PSA becomes undetectable, resuming upon rise (treatment holiday).

Missed dose

Take the missed dose as soon as remembered unless close to the next dose. Do not double up. If multiple doses are missed, consult your doctor.

Storage

Store at room temperature (68°F to 77°F / 20°C to 25°C), away from moisture and heat. Keep out of reach of children.

Dosage for enzalutamide

Condition	Adult Dosage	Notes
Metastatic CRPC	160 mg once daily	Monotherapy or with ADT
Non-metastatic CRPC	160 mg once daily	High-risk no-mets
mCSPC	160 mg once daily + ADT	Combination therapy
nmHSPC high-risk BCR	160 mg once daily ± leuprolide	Per EMBARK; unsuitable for RT

Getting the most from your treatment

• Attend all doctor appointments for blood tests and scans to monitor PSA and progression.
• Avoid grapefruit juice, as it may increase drug levels and side effects.
• Maintain a healthy diet, exercise, and bone health with calcium/vitamin D if on long-term therapy.
• Inform your doctor of all medications to avoid interactions, especially with strong CYP2C8 or CYP3A4 inhibitors/inducers.
• Regularly assess treatment response; discuss treatment holidays if eligible.

Side effects of enzalutamide

Common side effects are manageable but require monitoring. Serious effects like seizures occur in about 1% of patients.

Common side effects

• Fatigue (up to 34%)
• Hot flushes
• Diarrhea
• Musculoskeletal pain
• Headache
• Gynecomastia (breast enlargement/tenderness)
• Decreased appetite, weight loss

Serious side effects

• Seizures: Risk factors include brain metastases, head trauma. Discontinue if occurs.
• Posterior reversible encephalopathy syndrome (PRES): Rare; symptoms include headache, seizures, confusion.
• Rhabdomyolysis: Muscle breakdown; monitor for pain/weakness.
• Falls/Fractures: Due to muscle weakness, fatigue.
• Hypertension and cardiac issues.

Report persistent or worsening symptoms immediately. In trials, quality of life was preserved with enzalutamide plus ADT.

How to cope with side effects of enzalutamide

• Fatigue: Rest, light exercise, balanced diet.
• Hot flushes: Dress in layers, avoid triggers like caffeine.
• Diarrhea: Hydrate, eat bland foods; seek anti-diarrheals if needed.
• Pain: Over-the-counter analgesics; physical therapy.
• Muscle weakness: Strength training, fall precautions.
• Seizure risk: Avoid driving if at risk; discuss anticonvulsants.

Precautions while taking enzalutamide

• Contraindicated in pregnancy (teratogenic); use contraception for patients and female partners.
• Monitor blood pressure, liver function, PSA regularly.
• Avoid in uncontrolled hypertension or seizure history without specialist advice.
• Drug interactions: Adjust dose with CYP2C8 inhibitors (e.g., gemfibrozil) to 80 mg; avoid strong inducers (e.g., rifampin).

Pregnancy and breastfeeding

Enzalutamide causes fetal harm. Men must use effective contraception during treatment and for 3 months after. Advise female partners of potential risk.

Other medicines, food, drink, and enzalutamide

• Interactions: CYP3A4 inducers (e.g., phenytoin) reduce efficacy; inhibitors increase exposure.
• Avoid St. John’s wort, grapefruit.
• Inform doctor of warfarin use (INR monitoring needed).

Common questions about enzalutamide

Who can and cannot take enzalutamide tablets?

Adults with confirmed prostate cancer diagnoses per above indications. Not for women or children. Caution in seizure disorders, liver impairment.

How and when will you take enzalutamide tablets?

Once daily, 160 mg, anytime. Consistent timing aids adherence.

How long do you take enzalutamide tablets for?

Until progression or intolerance; potentially years with holidays.

Is enzalutamide a chemotherapy treatment?

No, it’s targeted hormone therapy, not cytotoxic chemo.

Does enzalutamide affect fertility?

May impair fertility; discuss sperm banking pre-treatment.

Can you drive or ride a bike on enzalutamide?

Yes, unless seizures or dizziness occur.

Can you drink alcohol on enzalutamide?

Moderate alcohol likely fine; consult doctor.

Id=”frequently-asked-questions”>Frequently asked questions about enzalutamide

Will enzalutamide shrink my prostate cancer?

It slows growth and delays spread; PSA reductions common.

What if I forget to take a dose?

Take soon as possible; skip if near next dose. No doubling.

Are there simpler alternatives?

Discuss with oncologist; options like abiraterone, apalutamide exist.

Will I have side effects that mean I have to stop?

Most tolerate; dose reduction to 120 mg or 80 mg possible.