Table of Contents
The treatment for prostate cancer involved lowering the levels of the male hormone testosterone using drugs called luteinising hormone-releasing hormone (LHRH) agonists. This was done because it was thought that testosterone stimulated prostate cancer cells to grow. However, there is no evidence to suggest that testosterone promotes cancer.
It was noted, in earlier research, that high doses of testosterone actually could reduce the growth of and kill cancer cells. The mechanism of this isn't known, but it was noted that increased testosterone interfered with part of the cell division process in cancer cells, called DNA licensing, which seemed to cause prostate cancer cells to make breaks in their DNA and die. What was also noted was a phenomenon known as senescence, which meant that the cancer cells were present but didn’t cause any issues.
In the RESTORE study which is still ongoing, 47 men with prostate cancer that was resistant to castration and that had started to metastasise to other parts of the body, and who showed no symptoms but whose disease had become resistant to treatment with either enzalutamide (in 30 patients) or abiraterone (in 17 patients), received a large dose of testosterone (400 mg) that was injected intramuscularly every 28 days. These patients still continued with their LHRH agonist therapy, to inhibit testosterone that was produced by the testicles, and they stopped taking enzalutamide or abiraterone (androgen receptor signalling inhibitors that cause chemical castration).
The aim of this study was to rapidly expose the cancer cells with very high and then followed by very low levels of testosterone. This form of therapy is known as bipolar androgen therapy (BAT) because of these alternating extremes in testosterone levels. The men that showed declining PSA levels or stable disease continued with BAT after three cycles. If the metastatic disease then started to progress, they were treated again with enzalutamide or abiraterone.
The aim of the study is to still use 60 men with castration-resistant metastatic prostate cancer, but the following findings have already been made on the 47 men that were used.
- Prostate specific antigen (PSA) levels fell in around 40% of men, and in about 30% of them levels fell by more than 50%.
- Prostatic masses shrank in some men.
- In several test subjects the disease didn't advance. This included men whose disease continued to be stable for more than 12 months.
- One man may appear to have been cured because his PSA levels dropped to 0 after three months and have remained so after 22 cycles of treatment, with no trace of the disease being present.
- Some men reported other positive outcomes including increased energy and muscle strength and decreased fatigue.
The clinical significance
The study is still in its research phase and needs to be completed before the full results are made available, but the results are unexpected and exciting.
Since the study is in its early stages, the researchers are still trying to figure out how BAT works and how to incorporate it into the treatment paradigm for prostate cancer.
A randomised trial in the United States using multiple centres, called TRANSFORMER, is comparing BAT to enzalutamide in 111 men (target group is 180) diagnosed with castration-resistant metastatic prostate cancer whose disease had advanced after receiving abiraterone. The researchers state that if they find that testosterone is superior to enzalutamide, they will move onto larger clinical trials.