CHICAGO—A six-month course of the targeted therapy for prostate cancer (PCa) with a drug abiraterone (Zytiga), in addition to standard hormonal therapy before radical prostatectomy, may help eliminate or nearly eliminate cancer in some men with localized high-risk PCa, according to a randomized phase 2 study presented at the American Society for Clinical Oncology 2012 annual meeting.

The study marks the first time abiraterone (a drug that is FDA approved for treating advanced PCa) has been explored for the treatment of earlier stages of prostate cancer, including in the neoadjuvant setting.

“For this proportion of patients with high-risk disease to have very little to no detectable cancer in the prostate after six months of therapy is dramatic,” said lead researcher Mary-Ellen Taplin, MD, Associate Professor of Medicine at Harvard Medical School and a medical oncologist at Dana-Farber Cancer Institute in Boston. “Our findings suggest that this combination therapy approach could improve outcomes for a substantial number of men, but larger, long-term trials are needed to confirm this approach.”

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Localized high-risk disease is defined as prostate cancer in men with a PSA level above 20, high-grade disease (a Gleason score of 8 or more), or stage T3 disease.  Previous studies have shown that use of standard hormonal therapy alone, including treatment with leuprolide, before surgery had limited benefits for men with localized high-risk PCa.

In the current study, Dr. Taplin and her colleagues evaluated the effect of adding abiraterone to leuprolide in two groups of men with localized high-risk disease: Group A included 27 men who received leuprolide hormonal therapy for 12 weeks followed by leuprolide plus abiraterone for another 12 weeks.  The second group (Group B) included 29 men who received both abiraterone and leuprolide for the entire 24-week period. Prostate surgery was performed in all men after 24 weeks of therapy, and the tissue was examined for evidence of cancer.

Among men in Group B (24 weeks of abiraterone therapy), 34% had either complete elimination (three patients) or nearly complete elimination (seven patients) of their cancer upon surgery. In Group A (12 weeks of abiraterone therapy), 15% of men had either complete elimination (one patient) or nearly complete elimination (three patients) of their cancer upon surgery. Therapy was well-tolerated by both groups.

“Very high-risk cancers localized to the prostate are rarely cured by prostatectomy alone,” Dr. Taplin said. “Therapies that combine surgery with older androgen-inhibiting drugs have not historically improved outcomes. This unmet need has given rise to efforts to develop new drugs capable of more completely reducing androgen levels within the prostate tumors.”

Conventional therapies target androgen production in the testes and adrenal glands, but not within the tumor itself. Abiraterone acetate is capable of blocking androgen production in all three sites. The clinical benefit of intensive androgen deprivation therapy, either before or after prostatectomy, will need to be validated in prospective, randomized clinical trials, but these data suggest a benefit for some men.

E. David Crawford, MD, Professor of Surgery/Urology/Radiation Oncology at the University of Colorado in Denver, said the new study is a very important and could affect clinical practice if the findings are confirmed. “This is an exciting study which is moving one of our very powerful drugs up in therapy,” Dr. Crawford said. “With all the concerns about over diagnosis and treatment, this study focuses where we need to make an impact. However this is a small study and further ones will be needed.”