BAT update (for men on permanent ADT)

No, it's not about the Caped Crusader. Bipolar Androgen Therapy (BAT) is alternating treatments of ADT with high-dose testosterone. In theory, the high doses of testosterone will help the patient feel better and perhaps offset some of the symptoms of ADT (e.g., loss of libido, hot flashes, bone loss, lean muscle loss, mental symptoms). It also may slow down the development of castration resistance. It is in clinical trials at Johns Hopkins.

In this update, they report on 29 patients who responded well to 6 months of ADT (meaning that their PSA went down to <4 ng/ml). They then received 3 months of testosterone injections, and then 3 months of ADT, cycled for a total of 18 months.

They report that 59% were still able to achieve their PSA goal (<4) at the end of 18 months. Of the 10 patients with detectable metastases at the start, they had shrunk completely in 4, and partially in 4. Six patients had metastatic progression. Evaluations of quality of life improved.

Bipolar androgen therapy for men with androgen ablation naïve prostate cancer: Results from the phase II BATMAN study

- Allen

Allen,

Would this be a possible option for those like me on IHT on the off season of HT? Very interesting.

Jerry L,

It's still in the exploratory stage. JH has a couple of open clinical trials using BAT. One to see if it is superior to Xtandi for mCRPC, the other to see whether it can re-sensitize men to Xtandi or Zytiga:

Testosterone Revival Abolishes Negative Symptoms, Fosters Objective Response and Modulates Enzalutamide Resistance (Transformer)

RE-sensitizing With Supraphysiologic Testosterone to Overcome REsistant (The RESTORE Study)

Andrew, bipolar people are BATty.

Dan said...
Does that t mean that treatment with Zytiga could possibly be re-started if or when that day comes when it stops working effectively?

That's their hypothesis that they are testing in their clinical trial. It is also possible that Taxotere or Jevtana may restore sensitivity to Zytiga and Xtandi in some cases.

Dan said...
Of the 10 patients with detectable metastases at the start, they had shrunk completely in 4, and partially in 4. Six patients had metastatic progression." Is there an overlap there?(since that equals fourteen)

The trial included "asymptomatic hormone-sensitive PC patients with low metastatic burden or non-metastatic biochemically recurrent disease were enrolled."

Ten patients had detectable mets from the start, and after BAT, they shrunk completely or partially in 8 of them (4+4). It is unclear from the abstract whether the remaining 2 patients had no met shrinkage (i.e., they stayed the same) or whether they progressed (or one did each).

But the trial also included 29-10=19 patients who did not have detectable metastases at the start. So, at least 4 of them, and maybe 6 of them, had metastatic progression at 18 months. So, 13-15 of the 19 (68-79%) of the recurrent men with no detectable mets still had no detectable mets after 18 months of BAT.

- Allen

Allen,
I know in your neck of the woods is Dr. Bob Leibowitz who has been touting for years extreme testosterone replacement therapy in men with metastatic disease that have not fare well on traditional approaches. He talks about raising a buys T level to as high as 4000 and getting a positive disease response. I know it's not the same as you are posting here, at least not completely. Leibowitz suggesting alternation of estradiol and high dose TRT since at least the mid 2000's. I've linked such a discussion from 2009/2010 era and he recently sent me a DVD where he is even more strong about it today. This discussion is about two hours long but still intriguing.

/www.youtube.com/watch?v=U7Q5fU4W2Rw

I spoke to a few docs about this and they simply say we need such trials testing extreme testosterone dosing for treatment of mCRPC patient subsets.

I find it interesting that we sometimes hang our hat on a standard of care such as ADT, and we have known cases of men responding to the exact opposite. Estradiol was demonized in the early going as being too toxic and ineffective and yet we have ongoing trials and results showing promise depending on how it is used.

Thanks for this post. It puts Dr Bob back on the map in some ways.

Thanks TA- very interesting.

In your opinion, is this therapy appropriate before the appearance of CRPC? Is it feasible that it can/will substitute for current standard of care for mCSPC (ADT + docetaxel and wait for CR to show up...). The idea of escaping ADT forever is very exciting.

thanks

rf

NJ Jon - That's great that it worked for you. Please continue to keep us posted.

rockyfords - good questions!

rockyfords said...
is this therapy appropriate before the appearance of CRPC?

That's what this pilot test was -- all the men still responded to ADT. We know that men who have historically had low natural levels of testosterone (hypogonadal) are more likely to develop prostate cancer, and more aggressive prostate cancer, than men with normal T levels. T plays a role in keeping healthy prostate cells healthy.I think that many doctors now think of cancer as a tissue-based disease rather than a cell-based disease. That means that within a tumor, healthy prostate cells communicate with cancerous prostate cells and influence them to become less cancerous, and vice versa. The hope is that maintaining or increasing T levels will shift the equilibrium towards the healthy cells. Similarly, within any given tumor, there are some cancer cells that are hormone-sensitive (HS) and some are castration-resistant (CR). The two types influence each other in a dynamic equilibrium that gradually shifts over time towards more cells becoming CR. So the hope there too is that high T levels will increase the relative survival of the HS cells, and that will cause some of the CR cells to become HS. Then, alternating with periods of ADT will reduce the cancer load.

So that was a long way of saying, "maybe" in answer to your question. The hypothesis is that it might work even better before the equilibrium has shifted towards predominant CR. This was only a pilot test, hopefully there will be an expanded trial.

rockyfords said...
Is it feasible that it can/will substitute for current standard of care for mCSPC (ADT + docetaxel and wait for CR to show up...). The idea of escaping ADT forever is very exciting.

Maybe, but I doubt that it will ever be entirely a substitute. ADT and docetaxel are very potent at reducing the cancer load. T supplementation, if it is shown to have an effect in the BAT trials, so far only seems to be useful in addition to rather than instead of. But alternating therapies might become the standard of care someday. At the very least, even if it doesn't increase survival, it may increase quality of life. Probably, there are some patient characteristics we have yet to identify that will make someone a good candidate and others not. It's a very diverse disease across patients and a rapidly evolving disease within any given patient.

- Allen

Post Edited (Tall Allen) : 8/12/2016 11:28:42 AM (GMT-6)

TA,
This topic came up at SWOG on more than one occasion. But we couldn't fund such a trial. That would have to come from the NCI steering committee and get funded through NIH. Unless one of the TRT pharm.'s wants to take it on which is unlikely.

The problem with the JHU trial is that it won't lead to a change in treatment protocol guidelines. It will take a Phase III trial in men over a ten years+ period. Perhaps a more likely trial will be men with mets. This will shorten the timeline needed for results and that will reduce the costs associated with such a trial.

But this is a very interesting topic to me.

Excellent question Allen...

I should do a post on how SWOG works on my board for easy linking and I will when I get the time. Being a part of SWOG has been one of the best experiences in my life. Here's from our greeting page

tinyurl.com/z8r7svk

We are heavily funded by the federal government and as a Co-Op we are an extension of the NCI like four others. That stated we can get funding elsewhere such as the Pharma industry to test their drugs with the intention of them reaching the market. Since we are supposed to be an objective group of peer reviewers our clinical trials are very highly respected. But the meetings we attend, the group employees, and the administration of our group is funded largely by The Hope Foundation. They pay for all my trips and hotels and for the doctors travel and hotels. The doctors at SWOG are not paid by SWOG. Most are a member because it's an honor to be here and they have earned the opportunity to be on the panels.

Funding such a trial as you suggest could be done by SWOG but we really have to follow a protocol at the NCI that tends to be what we call "politicology" or "oncolotics". There is a GU Steering Committee that decides what gets funded and what does not. We can propose trials and we do a lot of them. But we usually are "steered" by that committee.

(Edited to fix links)

Post Edited (Tony Crispino) : 8/12/2016 6:39:45 PM (GMT-6)

Why not me is for a lot of reasons. NCI has a full pipeline as does SWOG. What JHU is likely to do from here is propose a Phase III trial with their results and have that trial be routed through NCI to the NCI Co-Ops. Likely ECOG because they are an active NCTN member institution there. That would be the correct oncolotics to getting it done.

Right now our roster is pretty full. Our next live meeting is in Chicago Sept 14-17. I've seen the trials that are being reviewed and I like them all.