Combining drugs for better prostate cancer treatment?

AFT-19 trial: Investigating androgen blockade intensification in prostate cancer.

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Combining testosterone-blocking drugs in prostate cancer patients is more effective than using a single medicine, says a University of California San Francisco-led phase 3 trial. This approach extends the time between treatments without prolonging recovery. Prostate cancer, affecting 1 in 8 men and causing 34,000 deaths annually in the US, is typically treated with testosterone-lowering drugs for a specific duration.

Rahul Aggarwal, MD, is a professor at the UCSF School of Medicine and the lead author of the paper, said, “This adds to a growing body of evidence in favor of more intensive testosterone-blocking therapy in patients with higher-risk prostate cancer.” 

Published in January 2024, the researchers advocate for more aggressive treatment in prostate cancer cases. Examining patients who had undergone prostate cancer surgery but experienced a relapse indicated by elevated PSA levels, the study’s initial results were presented at the European Society for Medical Oncology in September 2022.

Aggarwal said, “We looked at patients who had a fast rise in their PSA — an indicator of a higher-risk form of relapsed prostate cancer. Our goal was to test several different hormone therapy strategies to find the best approach in terms of delaying the cancer’s progression.”

From 2017 to 2022, 503 prostate cancer patients were randomly given either a single testosterone-lowering therapy or a combination with one or two additional FDA-approved drugs—the assigned treatment, whether single or combined, significantly reduced testosterone, slowing cancer growth. However, side effects like fatigue and decreased libido occurred. Patients receiving additional drugs stayed cancer-free with low PSA levels longer than those on a single pill during their year-long treatment.

After treatment, patients on combination therapies recovered testosterone levels as fast as those on a single drug. The researchers are now analyzing detailed data on side effects, recovery experiences, and overall well-being. Dr. Aggarwal emphasizes that with this study’s evidence, combination hormone therapy should be considered a standard for prostate cancer patients with high-risk relapse after prior treatment.

This research could potentially pave the way for a more robust and targeted approach to prostate cancer treatment, offering hope for improved outcomes for patients facing high-risk relapse situations.

Journal reference:

  1. Rahul Aggarwal, Glenn Heller, et al., PRESTO: A Phase III, Open-Label Study of Intensification of Androgen Blockade in Patients With High-Risk Biochemically Relapsed Castration-Sensitive Prostate Cancer (AFT-19). Journal of Clinical Oncology. DOI: 10.1200/JCO.23.01157.

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