BAT: transformer trial

[kaptank]

G’day comrades

This is another short post on developments in Bipolar Androgen Therapy (BAT). It’s again mostly from the Johns Hopkins groups around Denmeade and Shweizer. Early results from the TRANSFORMER trial. (Testosterone Revival Abolishes Negative Symptoms, Fosters Objective Response and Modulates Enzalutamide Resistance (Transformer) – what violence we do to language in science!) In this one they took about 200 asymptomatic patients who had progressed on abiraterone and had not taken enzalutamide. Split into 2 groups. One goes straight on to enza, the other does basic BAT (Shot of supra T once a month) All remain on primary ADT. So it’s a direct comparison of enza and BAT. Interestingly the end results in the usual terms, time to progression etc, showed no significant difference. Antiandrogen and superandrogen about the same. Each end of the androgen spectrum can be effective.(Huggins hypothesised as much)

When patients progressed on 1 arm of the treatment they crossed over to the other. Fail enza, start BAT. Fail BAT start enza. Those who failed enza and started BAT did about as well as the original BAT group. But those who failed BAT and started enza did very significantly better. BAT was safe. The primary conclusion was that for patients that fail abiraterone, doing BAT sensitises the PCa to enza to a very significant degree and BAT has potential to reverse resistance to antiandrogen(s?)

ascopubs.org/doi/abs/10.120...

urotoday.com/conference-hig...

urotoday.com/video-lectures...

[LearnAll]

BAT seems a promising treatment . Men who are NOT suitable candidates for BAT are(1) One who have active symptoms such as bone pain, spinal compression or urinary retention/obstruction.

(2) Those who have prior history of thromboembolism or high risk for clot formation.

Kaptank..Are there other exclusions

Also, How effective this BAT is for men who are already Androgen Independent ? And the ones who have reached treatment emergent neuroendocrine transformation ?

Please add to our knowledge.

[kaptank in reply to LearnAll]

As best I know, no one has tried it with neuroendocrine. I think that might be risky - it might react differently but we really don't know. I would think that because ne doesn't respond well to antiandrogens in the first place that BAT would be less useful and possibly harmful. By androgen independent I assume you mean castrate resistant and all trials so far have been on CRPCa. There is a suspicion (that's all it is) that it may be useful for hormone sensitive cases to prevent resistance forming in the first place. Patrick has thought about this. It seems to be most useful for reversing or preventing resistance to antiandrogen treatments but there are ongoing trials combining it with other treatments like PARP inhibitors or immunological treatments.

[LearnAll in reply to kaptank]

Thanks. The hypothesis that if we release the pressure of very low testosterone from time to time on androgen dependent cancer, they might retain their androgen dependent feature for a longer time. It is the same premise which we make when doing Intermittent ADT.I would be interested to know more about the risk of sudden surge of testosterone...I mean.. Can this cause sudden flare in symptoms of prostate cancer in asymptomatic men ?

[kaptank in reply to LearnAll]

According to Denmeade, no they did not see a sudden flare of PCa. The worst case was that the cancer progressed as it had before, as if nothing was done. Note that the first injection of T often causes a flare in PSA but this is not because PCa has gone berserk.

[kaptank in reply to LearnAll]

Supra T can cause a pain flare for about 1-2 weeks as T falls. Assumed to be an inflammatory effect rather than an underlying rapid progression of PCa.

[taylor123 in reply to kaptank]

Does the PSA often fall after the initial flare ?

[kaptank in reply to taylor123]

In about 2 months it is usually about back to where it began. But great variability. In 1 case I had PSA elevated for 2 months, decided it was a failure and got a new onco. Test at 4 months had it back to where it was and scan at that time showed slow growth over the past 3 years. False positive. I certainly found that PSA results jump around a lot more when T is in the equation.

[taylor123]

This is very interesting and useful because my Dad is in exactly the same situation as the participants right now.

Thanks for posting.