New Options in Androgen Therapy

Although hormone therapy is the mainstay for treating metastatic prostate cancer, it can only slow the progress of the cancer for so long, a reality that heightens the importance of any new way of manipulating testosterone or its activity. That’s why preliminary results of two new targeted therapies, now in late-stage clinical trials, hold so much promise for men with hormone-refractory, or castration-resistant, prostate cancer.

Abiraterone is an orally administered compound that acts on the “supply side” of the testosterone cycle—inhibiting a key enzyme involved in the final steps of testosterone production. It helps, at least temporarily, to “starve” the prostate cancer cells by blocking the production of testosterone, which they depend on to grow.

Abiraterone does this by blocking testosterone production, not only in the testes, but also in the adrenal glands, which produce about 5 percent of the hormone.

In phase 2 trials of men whose cancer had spread, abiraterone significantly shrank the tumors and enabled two-thirds of the men to live pain-free for an average of eight months. Phase 3 trials at more than 150 hospitals worldwide are now looking at the effects of the compound in 1,300 men, one of the largest trials ever for advanced prostate cancer.

Another new targeted therapy, MDV-3100, attacks prostate tumor cells themselves, disrupting the pathway for the uptake of testos- terone. The oral drug not only prevents the hormone from binding to the cell’s androgen receptor, but also helps induce the cellular self-destruction of the tumor cell, a process called apoptosis. In phase 2 trials, the compound stabilized or shrank tumors in 22 to 56 percent of the patients and substantially lowered PSA levels for up to 41 weeks in more than half of all patients. Phase 3 trials are under way in the United States and 14 other countries.

“In the past, we didn’t have many options once prostate cancer became resistant to hormonal treatments,” says Winston Tan, MD, senior consultant for the Mayo Clinic Florida. “These new drugs—and others that are still in clinical trials—are going to change the landscape for the treatment of men with metastatic, castrate-resistant prostate cancer.”

More information on recent results of clinical trials and enrollment in ongoing trials is available at www.cancer.gov/clinicaltrials.