A drug tested in a clinical trial shows a powerful effect in men with prostate cancer whose prostate-specific antigen (PSA) levels continue to escalate despite hormone therapy.

In the phase 3 trial, which companies Pfizer and Astellas Pharma sponsored, enzalutamide was shown to lower the risk of metastasis or death by 71% when compared with a placebo.

Enzalutamide (brand name Xtandi) is approved in the United States to treat metastatic prostate cancer that is "castrate resistant."

The new trial tested the effectiveness of the drug in aggressive, but not metastatic, castrate-resistant disease.

The drug is currently under review in the US for approval to include men who have this disease.

The scientists report the findings of the trial in a paper now published in The New England Journal of Medicine.

Lead study author Professor Maha Hussain, at Northwestern University Feinberg School of Medicine in Chicago, IL, says that she is "delighted" with the results. She led the trial while she was at the University of Michigan in Ann Arbor.

"Not only did the drug reduce cancer spread," she adds, "but many other disease-related effects were [also] impacted."

Castrate-resistant nonmetastatic cancer

Castrate-resistant prostate cancer, also called castration-resistant, means that the cancer continues to grow even after hormone treatment has greatly reduced levels of testosterone in the body.

Prostate cancer cells need testosterone to grow. At first, the cancer may respond well to treatment that reduces the male hormone, but then it often becomes resistant.

There are currently no effective treatments able to improve prospects once the cancer reaches this stage.

Metastatic prostate cancer means that the cancer has outgrown the primary tumor—that is, the place where it started—in the prostate, which is a small gland between the bladder and the penis.

Through the metastasis process, the cancer invades tissue in and around the prostate. It also sends out migrating cells that give rise to secondary tumors in more remote parts of the body.

Nonmetastatic cancer is confined to the primary site and has not (yet) undergone metastasis.

Drug blocks hormone receptor

Enzalutamide works by blocking the ability of prostate cancer cells to feed on testosterone, as well as other substances that are similar to it, by disabling the cell receptor that binds to the hormone. The cancer cells either die or go into a dormant state.

While hormone therapy for prostate cancer reduces levels of testosterone, it does not shut down all sources of it in the body. Professor Hussain says that "even a whiff of male hormone stimulates the cancer."

"By treating men earlier when they have less cancer, the drug can be more effective."

–Professor Maha Hussain

The trial tested the effects of enzalutamide in 1,400 men with nonmetastatic prostate cancer whose PSA "levels had doubled in 10 months or less" despite undergoing hormone-reducing therapy, which they continued with through the study.

PSA is a protein that is produced by normal and cancer cells in the prostate. It is used as a measure of disease progression in men with prostate cancer.

The men received either a single 160-milligram dose of enzalutamide or placebo once per day. For every two men who took enzalutamide, one took the placebo.

The authors note that "[t]he median metastasis-free survival was 36.6 months in the enzalutamide group vs 14.7 months in the placebo group."

'Delayed reappearance of cancer'

Compared with those who took the placebo, men who took enzalutamide had a 71% reduced risk of their cancer becoming metastatic or of dying before the end of the 3-year trial.

The drug also postponed cancer re-emergence for nearly 2 years compared with the placebo. And, at the end of the trial, the men who were on the placebo switched to enzalutamide.

"Our goal was to see if we could delay the reappearance of cancer with the hope it will lead to prolonged life," Hussain explains.

The team still has to carry on with further follow-ups to assess the long-term impact of the drug on survival, but Professor Hussain says that "there are early positive trends."