Five More Months of Life

Advanced prostate cancer responds to Enzalutamide

(RxWiki News) Male hormones known as androgens, including testosterone, feed prostate cancer to help it grow and spread. So going after the processes that produce androgens is a key treatment strategy. 

An international phase III clinical trial of enzalutamide finds the drug gives men with advanced prostate cancer five more months of life.

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Researchers from around the world participated in this study which was conducted at 156 sites in 15 countries.

"This is a major advance. Not only do we see more survival benefit than from traditional chemotherapy, but the side effects of enzalutamide are much lower, said the study co-author, Thomas Flaig, MD, medical director of the University of Colorado Cancer Center's Clinical Investigations Shared Resource, in a press release announcing the results.

"It provides both more benefit and less harm – you get the quantification of more life, but also see quality of life improvements," said Dr. Flaig, who is also associate professor of medicine at the University of Colorado School of Medicine.

The study known as the AFFIRM (A Study Evaluating the Efficacy and Safety of the Investigational Drug MDV3100) involved about 1,200 men whose prostate cancer progressed despite treatment. When prostate cancer reaches this stage, it's known as castration-resistant prostate cancer.

All of the men in the study had received at least one round of chemotherapy.

For this study, some 800 participants, enrolled between September 2009 through November 2010, received a enzalutamide pill daily and the others had a placebo.

The men taking enzalutamide lived a median of 18.4 months, compared with 13.6 months for men who received a placebo.

Additionally, the disease took longer to progress in the treated patients - 8.3 months versus 2.9 months progression-free survival in those who did not receive the drug.

The most common side effects were fatigue, diarrhea and hot flashes.

Scientists found that the drug works by blocking prostate cancer's capacity for grabbing onto and feeding off of androgens.

The authors wrote, "In this phase III study, we found that enzalutamide, an oral androgen-receptor–signaling inhibitor, significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy by a median of 4.8 months and reduced the risk of death from any cause by 37 percent versus placebo."

Dr. Flaig described that prostate cancers have been seen as having two phases.

At first they depend on hormones to thrive. Then, in the second phase, many prostate cancers get to the point where hormones no longer play the key role in the disease. That's when stronger - and more toxic - chemotherapies are needed.

The second phase was thought to be untouchable with hormone-blocking drugs. This drug is changing that thinking.

"Enzalutamide is a key member of a half dozen new and emerging drugs and the challenge of the next five years is to discover how to best time and potentially combine these new agents.

But even at this early stage, Enzalutamide is a game changer," said Dr. Flaig.

Additional studies are under way with this drug and are in planning stages for the future.

This drug has not yet received approval from the U.S. Food & Drug Administration and is not currently available. However, phase III trials are the last hurdle before applying for FDA approval.

This study was published August 15 in The New England Journal of Medicine.

This work was supported by Medivation and Astellas Pharma Global Development, the makers of Enzalutamide.

A number of the authors disclosed financial relationships with pharmaceutical companies including those that funded this research. 

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Review Date: 
August 17, 2012