|| This Experimental Prostate Cancer Treatment Is Shrinking Tumors

This Experimental Prostate Cancer Treatment Is Shrinking Tumors

There may be new hope for men with this deadly disease

One day several years ago, Samuel Denmeade, M.D., a professor of oncology and urology at Johns Hopkins University, got a phone call from his home state of Ohio. The man on the other end was J. Bruce Hunsicker, an Akron-based lawyer with prostate cancer who had started a foundation to raise money for research into the disease. He wanted to connect with Dr. Denmeade, a leader in the field.

Hunsicker's nonprofit, the One-in-Six Foundation, eventually gave funding to Dr. Denmeade's lab. Although Hunsicker died of prostate cancer in 2010, his tenacity lives on. "It was inspiring to me to keep him in mind as we try to do all this stuff to make a difference and not make a profit," Dr. Denmeade says.

Dr. Denmeade has invested that money into a crazy idea that flips conventional wisdom about prostate cancer on its head.

Doctors have long looked to the hormone testosterone as a piece of the prostate cancer puzzle. Back in the 1940s, Charles Huggins, M.D., a professor at the University of Chicago, found that he could kill prostate cancer cells if he blocked testosterone production. Since then, oncologists have used a testosterone-reducing treatment known as androgen deprivation therapy in men with advanced prostate cancer. Kill the T, kill the cancer—or so the theory goes, because the cancer lives on androgen receptors that testosterone binds to.

In the lab, however, Dr. Denmeade's team found that the link between testosterone and prostate cancer may be more complex. When they exposed testosterone-starved cancer cells to a sudden high dose of T, the cancer was suppressed. That T influx, it seemed, might shock the cells and break their DNA.
Now Dr. Denmeade's team is trying this method, known as bipolar androgen therapy, in some men with advanced prostate cancer. Patients are injected with a "rapid shock" of testosterone to spike blood levels, which then taper off over the course of a month.

Giving high doses of testosterone to prostate cancer patients is novel, but if it works, the benefits could be big. Compared with treatments that cost thousands of dollars, testosterone is cheap and widely available.
In Dr. Denmeade's first small study, half the patients exhibited dips in a common cancer marker, and about a third had tumors shrink. The patients were happy, and some even regained sexual function.

As the next phase of research begins (it should end next year), Dr. Denmeade is trying to figure out which patients respond best to bipolar androgen therapy. It's being tested in 17 medical centers, but it's still too early to use the therapy outside a study setting.

Even if it works, Dr. Denmeade's bipolar androgen therapy won't necessarily be a cure-all for prostate cancer. "The disease is a whole bunch of different cells," says Eugene Kwon, M.D., a professor of immunology and urology at the Mayo Clinic. Some are sensitive to chemo, some to radiation, and some to hormone therapy. "The cell manipulations they're exploring are a slice of the pie when you talk about the spectrum of prostate cancer," he says.

Dr. Denmeade is cautiously optimistic. "There's a fine line between hope and hype," he says. But if further research deems the treatment a bust, he has more ideas.

This is an important mission: A projected 161,360 American men will be diagnosed with prostate cancer this year. Most will survive with treatment; some strategies are described below. Within five years of their diagnosis, however, up to 20 percent of patients will learn that their cancer has spread beyond the prostate and is defying treatment. This is when prostate cancer turns deadly. It will likely kill more than 26,000 men this year.

"There's a lot of media out there that says we shouldn't screen for prostate cancer, that we shouldn't treat prostate cancer, and that you're going to die with it, not of it. That's just not true," says Charles Ryan, M.D., a professor of urology at UC San Francisco. "There are plenty of men who suffer and die horrible deaths from prostate cancer. The key to understanding the difference is collecting data and making a risk-adapted decision."

Fortunately, a slew of new treatments are now available.

"There are things that didn't exist five years ago that are now standards of care," says Fred Saad, M.D., director of prostate cancer research at the Montreal Cancer Institute.

Men are living longer and better lives even with late-stage disease. For instance, the cancer-fighting drugs abiraterone acetate and enzalutamide were approved by the FDA in 2011 and 2012, respectively. In 2013, the FDA approved radium-223 dichloride, a form of radiation therapy for men whose cancer has spread to their bones. For men with certain genetic mutations, poly ADP-ribose polymerase (PARP) inhibitors—designated a "breakthrough therapy" by the FDA—can preferentially kill cancer cells.

Some centers now have imaging tests to track tumors every few months and see which treatments work.

Some offer genetic tests to personalize treatment. After all, not all prostate cancers are the same. One tumor can require a completely different protocol than the next.

"We can go from one therapy to another, so we're constantly trying to bring patients back into remission," says Dr. Saad. In other words, men with late-stage prostate cancer have more reason than ever to be optimistic.

If a doctor tells you that you're out of options, seek a second opinion, ideally from a specialized center for prostate cancer. "It's sad to say, but for some people, their end of the road is not necessarily the same as at other centers that are doing a lot of research," says Dr. Saad.


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