New treatment option for prostate cancer that has spread to the bones

By Peter Wehrwein

Prostate cancer starts in the prostate gland. Of course. But in more than 90% of men with advanced cases of the disease, the cancer spreads (metastasizes) to the bone. Bone disease and its complications are responsible for more deaths from prostate cancer than they are for many other types of cancer. That’s why there’s some real excitement about Xofigo, a new treatment for advanced prostate cancer that attacks the disease once it has spread to the bone.

“This is likely to be an important advance for patients and physicians who are in significant need of drugs that help address the problems of bone metastases,” says Dr. Marc Garnick, editor in chief of Harvard Medical School’s Annual Report on Prostate Diseases.

The FDA approved Xofigo in May 2013. The drug was in the news again recently after favorable final results from an important study were published in the July 18, 2013, issue of The New England Journal of Medicine.

Xofigo is the brand-name for radium-223 dichloride, which you’ll see frequently shortened to radium-223.

Today’s generation of cancer drugs gum up the machinery of cancer cells in all kinds of ways and with increasingly cancer-specific accuracy.

Radium-223 seems a little sci-fi. It goes after prostate cancer cells lurking in bone by zapping them high-energy alpha-particle radiation.

The alpha particles emitted by the compound are potent enough to wreak havoc on the DNA of those cells. But for all their punch, they travel just a tiny distance before petering out—less than 100 micrometers, which is about a quarter of the diameter of the period at the end of this sentence. As a result, the effects on bone marrow are limited, which means far fewer side effects

Radium-223 also has a relatively short half-life of about 11 days. And because of its chemical similarity to calcium, once in the body (it’s administered by injection into a vein), the drug travels to and stays in the bone.

“A bone-seeking calcium mimetic” is how researchers put it.

The newsworthy study in The New England Journal of Medicine was an industry-sponsored Phase 3 trial that included a total of 921 men with who were randomly assigned to receive either six intravenous injections of radium-223 or a like number of  injections of a placebo. The injections were given four weeks apart.

The trial and its results were notable for a several reasons. First, the main outcome was that men who assigned to receive radium-223 lived longer than men who received the placebo (14.9 months vs. 11.3 months). That difference may seem small, but remember that is a median and that these men had very advanced cancer. Also, overall survival is the gold standard outcome for Phase 3 trials like these.

Second, the trial was designed so the men who participated were also receiving the best standard of care at the same time. That’s important because it means the results will be more applicable to broad population of advanced cancer patients, rather than a select group on some very specialized regimen, say Dr. Garnick and others.

And third, notes Dr. Garnick, the investigators focused on symptomatic “real world” bone and skeletal events, rather than some arbitrarily defined, nonsymptomatic x-ray measurement of bone disease.

The FDA approved Xofigo for treatment of men with very advanced prostate cancer that has spread to the bone, not to other organs, and only after efforts to control prostate cancer by lowering testosterone levels have failed; unfortunately, the term for such cases is “castration-resistant prostate cancer”).

But Garnick and others believe there’s a good chance that Xofigo will eventually be used much earlier in the course of a man’s disease, and perhaps as first-line therapy after testosterone-lowering hasn’t worked.

“Xofigo is very impressive,” says Dr. Garnick. “Kudos to all involved in its development and the Phase 3 trial.”

Peter Wehrwein is a freelance writer and editor.