Xtandi (enzalutamide) is an oral medication that blocks testosterone from fueling prostate cancer growth. It works at multiple points in the signaling chain that cancer cells rely on to survive and multiply, making it one of the more comprehensive hormone-blocking treatments available. The FDA has approved it for several stages of prostate cancer, from early biochemical recurrence all the way to advanced metastatic disease.
How Xtandi Blocks Cancer Growth
Prostate cancer cells depend on male hormones, primarily testosterone, to grow. These hormones work by attaching to a protein inside the cancer cell called the androgen receptor, which then travels to the cell’s nucleus and switches on genes that tell the cell to divide. Xtandi disrupts this process at four distinct steps: it prevents testosterone from attaching to the receptor, stops the receptor from moving into the nucleus, blocks the receptor from binding to DNA, and prevents the cell from reading the growth signals. By hitting all four steps, Xtandi is more thorough than older hormone therapies that only block one part of the chain.
This is why Xtandi works even in cancers that have found ways to keep growing despite standard hormone therapy. Many prostate cancers eventually adapt to low testosterone levels by becoming hypersensitive to whatever small amounts remain. Xtandi’s multi-step blockade makes it harder for cancer cells to use that workaround.
Which Stages of Prostate Cancer It Treats
Xtandi is approved for a broader range of prostate cancer stages than many patients realize. It covers three main scenarios:
- Castration-resistant prostate cancer (CRPC): Cancer that keeps growing despite hormone therapy that lowers testosterone to very low levels. This includes both metastatic (spread to other parts of the body) and non-metastatic forms.
- Metastatic castration-sensitive prostate cancer (mCSPC): Cancer that has spread but still responds to standard hormone therapy. Here, Xtandi is added on top of hormone therapy to improve outcomes.
- Non-metastatic castration-sensitive prostate cancer with high-risk biochemical recurrence: Cancer that hasn’t visibly spread on scans but shows rising PSA levels after initial treatment, with features suggesting a high risk of eventual spread.
In practice, this means Xtandi can be part of a treatment plan at very different points in the disease, from relatively early stages through advanced cancer.
How Well It Works
The strongest survival data comes from a large clinical trial called ARCHES, which studied men with metastatic hormone-sensitive prostate cancer. Adding Xtandi to standard hormone therapy reduced the risk of death by 34% compared to hormone therapy alone. After five years of follow-up, that benefit held steady, with a 30% reduction in the risk of death. In both analyses, median overall survival hadn’t been reached in either group, meaning most patients in the trial were still alive at the time of analysis.
Xtandi also drives significant drops in PSA, the blood marker used to track prostate cancer activity. In studies of castration-resistant prostate cancer, patients on the standard dose saw their PSA levels drop by an average of 87%, and nearly half achieved a PSA decline of more than 90%. PSA isn’t a perfect measure of what’s happening with the cancer, but large sustained drops generally signal that treatment is working.
What Taking Xtandi Is Like
Xtandi is a daily oral medication, taken as capsules or tablets. It can be taken with or without food, which makes it relatively convenient compared to treatments that require infusions or injections. Most patients take it alongside ongoing hormone therapy rather than as a standalone treatment.
The most common side effects are fatigue, hot flashes, joint pain, decreased appetite, dizziness, headache, high blood pressure, and weight loss. These occur in at least 10% of patients and are noticeably more frequent than with a placebo. Fatigue tends to be the most prominent complaint and can range from mild tiredness to significant exhaustion that affects daily routines.
Serious Risks to Be Aware Of
Most side effects are manageable, but Xtandi carries a few serious risks worth understanding.
Seizures occur in about 0.4% of patients overall. In a separate study that specifically enrolled patients with risk factors for seizures (such as a history of brain injury, stroke, or certain medications), the rate was higher at 2.2%. Seizures can happen anywhere from two weeks to nearly two years after starting the drug, and patients who experience one are taken off it permanently. All seizures in the clinical trials resolved after stopping treatment.
Heart-related problems are another concern. Ischemic heart disease, which includes heart attacks and reduced blood flow to the heart, occurred in 2.7% of patients on Xtandi compared to 1.2% on placebo in combined trial data. Severe cases were uncommon but real: 0.4% of patients on Xtandi died from heart-related events versus 0.1% on placebo.
Falls and fractures are more common than many patients expect. Falls affected 10% of patients on Xtandi compared to 4% on placebo, and these weren’t related to seizures or loss of consciousness. Fractures occurred in 8% of Xtandi patients versus 3% on placebo. This is particularly relevant for older men who may already have thinning bones from long-term hormone therapy. Staying physically active, addressing fall hazards at home, and monitoring bone health become especially important while on this medication.
Why Xtandi Can Stop Working
Like most cancer treatments, Xtandi doesn’t work indefinitely for everyone. The most well-understood reason involves a genetic workaround that cancer cells can develop. Normally, Xtandi works by latching onto a specific part of the androgen receptor called the ligand-binding domain. Over time, some cancer cells start producing a shortened version of the receptor, known as AR-V7, that’s missing this domain entirely. Without the target Xtandi is designed to block, the drug can no longer prevent the receptor from doing its job. The shortened receptor stays permanently active, driving cancer growth regardless of Xtandi’s presence.
AR-V7 is the most common of these altered receptors found in castration-resistant prostate cancer, and its presence is associated with resistance not only to Xtandi but to other hormone-blocking treatments as well. When Xtandi stops controlling the cancer, oncologists typically shift to a different class of therapy, such as chemotherapy or targeted treatments that work through entirely different mechanisms.