Two prostate cancer patients who had been told their condition was inoperable are now cancer-free as the result of an experimental therapy, the Mayo Clinic in Rochester announced today.

“We were all pretty shocked,” says Dr. Eugene Kwon, an immunologist and urologist at Mayo and leader of the clinical trial in which the experimental therapy was being used. “These results were far beyond anything we ever envisioned.”

The two patients had a particular subset of prostate cancer that is very aggressive and deadly. Unlike most prostate cancer, which grows slowly and usually remains confined to the prostate gland, aggressive forms tend to advance and spread quickly. By the time the cancer is diagnosed, treatment is usually ineffectual. These aggressive prostate cancers are the second-leading cause of cancer death (after lung cancer) in American men.

A treatment that tricks the immune system
The clinical trial that the men were enrolled in was a Phase II study — one designed to see if a particular treatment is effective in a modest-sized group of people (usually 100 to 300) and thus deserving of a much larger, randomized Phase III trial. The agent being tested was an immunotherapeutic drug called MDX-010, or ipilimumab. It was given to the two men in combination with standard hormone therapy.

The men first received the hormone therapy, called androgen ablation, which blocks the body’s production of testosterone, thus shrinking their tumors somewhat. “It ignites a little immune response,” says Kwon. The response isn’t strong enough to fight off all cancer cells, however. That’s where the ipilimumab comes in. “It’s like pouring gasoline on a pilot light,” says Kwon. The ipilimumab tricks the immune response into “burning” long enough to overpower the cancer cells, he says.

A surgical surprise
Within weeks of treatment, the two men’s tumors could not be seen on MRIs. But the real surprise came when the first patient underwent surgery. Removing the prostate gland in advanced cases has not been shown to have any therapeutic benefits. But because of the remarkable MRI results — and the tenacious insistence of the wife of one of the patients — Kwon and his Mayo colleague, urologist and surgeon Michael Blute, MD, decided to go “off study” and operate.

When Blute opened the patient on the operating table, he saw a lot of blanched scar tissue — usually a sign of advanced cancer. He sent tissue samples to the pathology lab (standard procedure) and, while waiting for the results, went out to prepare the patient’s family for what he was sure was going to be bad news.

“But the pathologist came back saying he couldn’t find the cancer,” says Kwon. “They ended up removing the prostate. Not only could they not find cancer outside the prostate, they couldn’t find it inside either.”

Surgery on the second patient produced similar results. A year-and-a-half later, both patients are entirely off therapy and have no evidence of cancer, says Kwon.

Caveats
Much more research is needed, Kwon points out, to determine the precise mechanisms behind this treatment — and what the most effective dosages and ways of administering it might be. Kwon also points out that so far, only three of the 54 patients in the therapy arm of the clinical trial have demonstrated such dramatic results. “In this trial, we may have been working with sub-optimal doses,” he says.

This fall, Mayo intends to start a clinical trial using higher and repeated doses of ipilimumab in combination with hormone therapy. “If that moves in a promising direction, we’ll go on to Phase III trials,” says Kwon.