MINNEAPOLIS – The hormone testosterone, which fuels the growth of prostate cancer, unexpectedly stymies the disease in certain cases, according to researchers who found it made tumors more vulnerable to treatment in some patients.
Prostate cancer is the most common tumor in men. It typically kills after tumors stop responding to drugs that block the production of testosterone and its receptors. That approach, called androgen deprivation therapy, has been standard for 70 years.
“This is really the most lethal form of prostate cancer,” said Michael Schweizer, the study’s lead researcher from Fred Hutchinson Cancer Research Center in Seattle. “Once people progress to this stage, it’s when we start to worry that they’re at a much higher risk for dying from prostate cancer.”
In a trial of 16 patients, investigators used a new method, dubbed “biopolar androgen therapy,” to attack tumors that had built resistance. Patients were given monthly testosterone shots while simultaneously receiving drugs to block its natural production, creating huge swings in levels of the hormone.
The results, published Wednesday in the journal Science Translational Medicine, showed some success. Seven patients saw declines in levels of prostate-specific antigen, or PSA, linked to the cancer during treatment and 10 responded to conventional care after the experimental testosterone injections ended. Five men had their tumors shrink by half, including one whose cancer disappeared. Three patients have died since the study began in 2010.
“This was a small study and it was a weird idea to give men with prostate cancer testosterone,” said Samuel Denmeade, the senior author of the paper and an oncologist at Johns Hopkins Kimmel Cancer Center in Baltimore. “The results were unexpectedly promising, and we’ll need a lot more study. But this cycling on and off of testosterone could become a part of the treatment.”
It can have serious complications. One patient died during the trial from pneumonia linked to the chemotherapy that was part of the treatment approach. A prolonged erection, a possible side effect of testosterone therapy, led another patient to drop out of the trial.
The researchers exploited a vulnerability created as cancer cells adjust and become exquisitely sensitive in a low-testosterone environment. Previous lab work showed high testosterone can kill prostate cancer cells, though there wasn’t compelling explanation for how the process worked, Schweizer said. It may be that cancer cells that have adapted to the low- hormone environment can’t tolerate high levels of testosterone, according to an editorial summary that accompanied the paper.
The Johns Hopkins researchers have another study under way that will involve 60 patients, and a larger, nationwide study is slated to begin this spring, Denmeade said.