Recently there has been a number of posts and subsequent responses from members of Fight Prostate Cancer on Bipolar Androgen Therapy. This very recent UroToday video (see link) in which Professor Samuel Denmeade is interviewed by Alicia Morgans might be of interest to some on this forum.
In the interview Professor Denmeade discusses the TRANSFORMER trial and Bipolar Androgen Therapy (BAT) for prostate cancer. The trial, involving 200 patients, compared high-dose testosterone therapy to enzalutamide in treating hormone resistant prostate cancer. Dr Denmeade noted that surprisingly, both treatments showed similar efficacy with each offering about a six-month response duration but notably, patients who switched from testosterone to enzalutamide had a significantly higher and longer lasting response.
Professor Denmeade also re-capped the information he had presented at ASCO 2024 about the TRANSFORMER trial, a randomised study of 200 men, the largest trial done with the BAT approach. Half of the patients were treated with testosterone and half with enzalutamide - two exactly opposite treatments. The endpoint was that they worked the same. When patients at the end of the trial crossed over what was found was that those patients who had enzalutamide initially had about a 20% response that lasted three or four months. However, in those patients who were given testosterone first and then enzalutamide there was an 80% response that lasted about 11 months. Longer response and more people responded.
Professor Denmeade notes that from the TRANSFORMER trial and all studies with testosterone about 30% of patients respond with PSA going down which is typical of the response seen in prostate cancer.
Professor Denmeade discussed his presentation at ASCO and the results of blood tests developed which looked for DNA in the blood. The amount of DNA and the kind of DNA can predict the response. What was found was that the androgen receptor, the target of testosterone and androgen-blocking drugs, if it was quite high it seemed to predict that those patients responded better to testosterone. When it was low, those patients responded better to enzalutamide. So potentially a blood marker that could be used in the future to satisfy patients in terms of high testosterone or low. He also noted the potential of this blood marker to guide future trials.
Professor Denmeade, when asked about side effects noted that, "This is kind of a unique therapy because it actually makes people feel better. We don't have a good scale for that. So we saw men have improvements in fatigue and just overall energy and strength and sexual function, and we don't have a good grading system for that. So those are the favourable things we saw. We see blood counts get better." He noted that one concern at the beginning was that it would make the cancer grow faster but that wasn't the case. However, patients' cancer either stabilised or regressed. He noted that the paradox was that everyone would have thought it would have made it worse.
Professor Denmeade acknowledged that there are patients "out there doing it on their own" but he encourages patients who might be interested in BAT to talk to their doctor first and if their doctor isn't familiar with it, have the doctor reach out to someone like him or others familiar with this treatment.
Androgen Receptor Activity (ARA) for BAT