Xtandi (enzalutamide) is a prescription medication used to treat prostate cancer. It is FDA-approved for several stages of the disease, from early-stage cancer that hasn’t spread to advanced cancer that has metastasized to other parts of the body. The drug works by blocking the activity of male hormones that fuel prostate cancer growth, and it’s taken as a daily oral pill.
Approved Uses for Xtandi
Xtandi is approved for three broad categories of prostate cancer:
- Castration-resistant prostate cancer (CRPC): Cancer that continues to grow even after treatments that lower testosterone, whether or not it has spread beyond the prostate.
- Metastatic castration-sensitive prostate cancer (mCSPC): Cancer that has spread to other parts of the body but still responds to hormone-lowering therapy.
- Non-metastatic castration-sensitive prostate cancer with high-risk biochemical recurrence (nmCSPC with high-risk BCR): Cancer that hasn’t visibly spread on imaging, but PSA levels are rising in a pattern that suggests a high likelihood of future metastasis.
The most recent of these approvals came in November 2023, when the FDA expanded Xtandi’s label to include that last category. This was significant because it moved Xtandi earlier in the treatment timeline, giving it a role for men whose cancer shows warning signs of spreading but hasn’t done so yet.
In all of these settings, Xtandi is typically used alongside another form of hormone therapy that suppresses testosterone production, or after surgical removal of the testicles.
How Xtandi Works
Prostate cancer cells rely on male hormones, especially testosterone, to grow and survive. Standard hormone therapy works by reducing the amount of testosterone the body produces. But cancer cells can adapt, finding ways to keep using even very low levels of testosterone to fuel their growth. This is what makes cancer “castration-resistant.”
Xtandi attacks this problem at a different point. Instead of lowering testosterone levels, it blocks the receptor on cancer cells that testosterone binds to. It does this in three specific ways: it prevents testosterone from attaching to the receptor in the first place, it stops the receptor from changing shape in the way it needs to in order to become active, and it prevents the activated receptor from entering the cell’s nucleus where it would switch on genes that drive cancer growth. By disrupting all three steps, Xtandi is more thorough than older anti-androgen drugs at shutting down this signaling pathway.
How Well Does It Work?
In one of the key clinical trials (called PROSPER), men with non-metastatic castration-resistant prostate cancer who took Xtandi lived a median of 67 months before dying from any cause, compared to 56.3 months for men who took a placebo. That’s roughly an additional 11 months of overall survival. The drug also dramatically delayed the cancer from spreading: the risk of metastasis or death dropped by 71% compared to placebo.
These results are particularly meaningful because the men in this trial had cancer that wasn’t yet visible on scans but was showing signs of progression through rising PSA levels. Xtandi gave them significantly more time before the disease became metastatic.
How It’s Taken
The standard dose is 160 mg taken once a day, with or without food. It comes in 40 mg capsules and 40 mg or 80 mg tablets, so the exact number of pills depends on the formulation. Treatment continues until the cancer progresses or side effects become unmanageable.
Unlike chemotherapy, Xtandi doesn’t require visits to an infusion center. You take it at home as a daily pill, which for many patients is a more manageable routine.
Common Side Effects
Fatigue is by far the most common side effect. In clinical trials, roughly half of patients experienced tiredness or weakness. This isn’t the kind of fatigue you can simply sleep off; many patients describe it as a persistent lack of energy that affects daily activities.
Other side effects that affected at least 10% of patients in trials include:
- Hot flashes (18 to 20% of patients)
- Back pain and joint pain
- Decreased appetite and weight loss
- High blood pressure (6 to 14%, depending on the trial)
- Constipation and diarrhea
- Headache and dizziness
- Swelling in the hands or feet
- Upper respiratory infections
Most of these side effects are mild to moderate. They’re a direct consequence of blocking hormone signaling, so they overlap with many of the effects men experience from other forms of hormone therapy.
Seizure Risk
Seizures are a rare but serious concern with Xtandi. In controlled clinical trials, about 0.5% of patients (10 out of 2,051) experienced a seizure at the standard 160 mg dose. A dedicated safety study called UPWARD found a slightly higher rate of 1.1%, with 4 out of 366 patients having a confirmed seizure within the first four months of treatment. At higher experimental doses above 360 mg daily, the rate was notably higher at 2%, which is why the approved dose was set at 160 mg.
People with a history of seizures, brain injuries, strokes, or other conditions that lower the seizure threshold may face elevated risk. Certain medications that lower the seizure threshold can also be a concern when combined with Xtandi.
Drug Interactions
Xtandi is a strong activator of certain liver enzymes that break down other medications. This means it can reduce the effectiveness of a wide range of drugs by causing your body to metabolize them faster than normal. Blood thinners, some heart medications, certain antifungal drugs, and even some over-the-counter medications can be affected. If you’re starting Xtandi, your oncologist will review your full medication list and may need to adjust doses or switch certain prescriptions.