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One in eight men will be diagnosed with prostate cancer, the most common cancer in American men. And nearly half of all patients will develop metastatic disease or progress to metastatic castration-resistant prostate cancer. 

This advanced form of prostate cancer is often hard to treat, as it spreads throughout the body and is no longer responsive to hormone therapy. This is often because of resistance caused by increased CYP17A1 expression, an enzyme key to testosterone production. Abiraterone acetate, a CYP17A1 inhibitor, helps reduce prostate-specific antigen levels and improves survival, but patients can become resistant to the therapy.

To achieve better prostate cancer control and to delay the emergence of treatment resistance, researchers at Moffitt Cancer Center have developed a therapeutic strategy called adaptive therapy. In this approach, patient treatment is altered, stopped or reinitiated based on how the tumor responds to treatment.

Dr. Jingsong Zhang, medical oncologist in Moffitt’s Genitourinary Oncology Program

Dr. Jingsong Zhang, Genitourinary Oncology Program

“Since 2010, there have been eight drugs approved to treat advanced prostate cancer, but based on the cancer statistics, the mortality rate of prostate cancer is increasing every year,” said Dr. Jingsong Zhang, a medical oncologist in Moffitt’s Genitourinary Oncology Program. “So there is a need to develop a new treatment, as well as a new treatment strategy, for this disease.”

Zhang is the principal investigator of a phase 2a clinical trial that uses evolutionary theories and mathematical models to guide the treatment cycles with abiraterone for metastatic castration-resistant prostate cancer. He presented results at the American Association for Cancer Research Annual Meeting.

Participants were enrolled in the clinical trial after their prostate-specific antigen level declined to less than 50% of their baseline level with abiraterone as their frontline therapy treatment. The primary goal of the study was to look at the percentage of men who remain responsive to abiraterone after two adaptive treatment cycles. As well as looking at the overall survival rate of adaptive therapy compared to the standard of care dosing schedule for abiraterone. 

Between June 2015 and January 2019, 17 patients were enrolled in the clinical trial. Five completed at least five adaptive therapy cycles. The results showed that the adaptive therapy was possible in men who responded to the abiraterone as a frontline therapy for metastatic castration-resistant prostate cancer. The therapy also prolonged the time of cancer progression with less than 50% drug usage compared to the conventional continuous abiraterone. 

“For this group of patients, compared to the standard of care, not only did we show adaptive therapy with intermittent use of abiraterone can prolong the duration of tumor response, but we also prolonged the radiographic progression-free survival, as well as overall survival of these patients,” said Zhang.