BAT - Current Evidence and Next Steps

[marnieg46]

"We've been doing a lot of work at Johns Hopkins using high-dose testosterone therapies to treat patients with metastatic prostate cancer, " says Mark C Markowski, MD, PhD.

This comprehensive overview of bipolar androgen therapy (BAT), by Mark Markowski, MD, PhD, associate professor of oncology at Johns Hopkins University in Baltimore, Maryland, may be of interest to those wanting to know more about BAT, what it is and how it fits in the prostate cancer treatment paradigm. Dr Markowski discusses the advantages and disadvantages, trials that have evaluated the treatment and what some next steps may include.

Topics covered include:

Rationale behind bipolar androgen therapy and the theoretical advantages and disadvantages

Trials of BAT conducted to date

Disease states that should be considered for BAT

Impact of prior treatment on success

Predictors of response to BAT

Why hasn't it received more attention?

urologytimes.com/view/bipol...

[MateoBeach]

Thanks Marnie. Interesting to see the limited theory being developed step wise. But without exploring their assumptions. It does not take into consideration that BAT therapies may actually work better on Hormone Sensitive prostate cancer (mHSPC). This is demonstrated in my own response to BAT (extremely effective) and also seen in other individuals in this setting. The changes in androgen signal and MYC expression that cycle in opposite directions to high and low testosterone point to a better model for understanding and application. Certainly it is under utilized currently on many who could benefit. Paul

[marnieg46 in reply to MateoBeach]

Yes Paul. The limitation of the article, focussing solely on the metastatic cohort, ignoring all other situations was noted on another site, Can only be hoped that as it is starting, albeit very slowly, to move more into mainstream discussion it will open opportunities for those who might benefit to explore this option.

Trust you're doing well x

[cujoe in reply to MateoBeach]

Pablo - Good to see you feeling well enough to comment.

As you know well, the usual pathway of treatment approvals unfortunately typically starts with patients who are at a very advanced disease state and/or have failed available treatment options. As with BAT & PSMA theranostics, there is good reason to think that both will eventually be proven to be as - or possibly "more" - effective for hsPCa than for CR-disease.

Unfortunately, that leaves patients who follow developing therapies with the option to either stay with SOC until they become reach CR-status or, in the case of BAT, do as you and others who post here have done and develop their own BAT programs before they become CR, monitoring results with walk-in testing and essentially becoming rogue n=1 patients - possibly to be scorned by major cancer treatment centers everywhere. With PSMA therapies, if still HS, they are also left to do like you have done, and seek treatment outside the US. Not a very patient-centered system in either case, to say the least. But, as we eventually come to find, one we have to work within (and around) as we seek to get access to the best treatment alternatives in time-critical fashion to preserve both our QOL and our longevity.

I hope your PT is going well and that you will be back hiking and biking by summer's end. In the meantime. Please Stay Strong and Be Safe & Get Well, Ciao - Capt'n cujoe

* * *

PS - Thanks for the post, Marnie.

[Hidden]

I have been using BAT + ARSi the last 15 months controlling the disease. This concept should really be the SOC after entering the CRPC state while PSA is low. T is cheap and the se are positive, my hemo is now 16, used to be 12!

It is very hard for MDs who have preached remove T - the «fuel» of pCA - to accept and understand the effect on the AR in the BAT.

Especially that high T reduces the AR activity back to the pretreated level thus making the cells HS again.

After 3 cycles of BAT last spring the PSA dropped from 7 to 0.14 using Enza for 6 weeks.

Now - a year later- the PSA has increased again to 3 after 3 x of BAT cycles, I have been adding the PARPi Olaparib in 50% dose.

Results like this is not possible otherwise.

Even better - this treatment approach can continue.

The first time I sent info concerning BAT to my MD he said no, I w’ont give you T - it’s doping and forbildden by law in Norway.

He is now enthusiastic, especially eager to monitor the AR-V7 level which used to be 15%, now 0.

We can just post in different forums and show the results.

[addicted2cycling in reply to Hidden]

OsloN wrote -- " I have been using BAT + ARSi the last 15 months controlling the disease. This concept should really be the SOC after entering the CRPC state while PSA is low. T is cheap and the se are positive, my hemo is now 16, used to be 12! ... "

Hoping your results remain positive 👍👍for years to come.

Having had castration (2015) immediately for my G10 Right Half there's no vacation except during my *T* injections (2016) that I've cycled by following PSA and Axumin + Pylarify scans both of which have found recurrence in the remaining left half.

Remaining Hormone Sensitive and Metastasis FREE being my goal and using Cypionate, while controversial, has worked so far. 2018 saw a return of 3+3 and 3+4 spots in left half that were treated using IRE and stopping the injections allowing PSA < 1.0 and T < 2.5ng/dL. Starting the injections up again had a return to 1,600ng/dL after injection down to 450/500 ng/dL before another injection 2 weeks later. PSA held constant until 2023 with a rise to 3.0 then 6.0 only 2 months later at which time the PSMA PET/CT showed 3 spots in left half only this time the biopsy yielded all at 3+3. NO TREATMENT on the 3 spots and stopping the *T* injections has PSA<0.1 with T<2.5ng/dL. Will stay on vacation from *T* a bit longer then restart.

Soon to be 74yo maintaining an excellent diet with exercise being a priority hopefully continues to tip the scale in remaining HS.

[Ramp7]

Did your MO prescribe Olaparib?

[Hidden]

Yes, i have BRCA2 + ATM

[Maxone73 in reply to Hidden]

I am looking forward for some study that can clarify if being ATM mutant gives more sensitivity to BAT

[Hidden in reply to Maxone73]

ATM assists in SSB repair, PARPi prevents repair, but if BRCA2 is intact then this protein will repair the breaks. Hard to say if this has an impact on cell Survival.

[NPfisherman]

Marnie,

Thanks for posting this interesting article...

It took essentially 5 years for abiraterone to go from approved for MCRPC to tx for MHSPC... The studies on utilizing BAT in MHSPC needs done, so we can see if BAT is not inferior to current SOC for MHSPC. and where it should be sequenced in regards to establishing a new SOC involving BAT and MDT, and possibility to provide long remission/cure

As I say, we are the very beginning of the golden age of oncological research.... the next 5 years will be huge...

DD

[KocoPr in reply to NPfisherman]

I get the feeling that the research doctors are afraid to treat MHSPC for a one reasons.

To suggest a therapy that starts before CRPC is to suggest a minimal use of these very profitable drugs. Can you imagine the pressure to get funding for that heresy?

Here is one of the statements on the link provided above.

There did not appear to be an advantage of treating early vs later; it seemed like if the testosterone was going to work, it was going to work for however long it was going to work for, irrespective of the number of therapies. So, it's not exactly clear where we should implement it. It seems to work reasonably well wherever we choose to use it. But I think, in a little bit more general terms, mixing in the bipolar androgen after an AR-targeted therapy will sensitize patients to that next line of AR-targeted therapy. We've learned over the years that trying to move from an oral AR-targeted therapy like abiraterone straight to enzalutamide is not the best treatment approach.

No mention of earlier to mean hormone sensitive. It is just frustrating.

[NPfisherman in reply to KocoPr]

Sometimes, you feel like the Science is getting there, and then again...It is frustrating... they always start out with CRPC, because it is the deadlier form of the disease and that is right in my mind, but yeah, after you determine efficacy in CRPC (confirmed), then start on HSPC...I do wonder how Russ at Cancer Hackers lab is doing... As the Dog of Terror says,"Be safe and well..."

[Justfor_ in reply to KocoPr]

Money drives-obstructs innovation. A push-pull circuit and "circuit".

[PCaWarrior]

22 clinical trials and counting. It's closing in. I feel that one of the largest impediments is money. For-profit pharmaceutical companies aren't going to fund trials that involve drugs that won't make a profit. If a director authorized it, he'd be fired very quickly by the board and shareholders. It is what it is.

What I have seen lately is more and more trials include profitable drugs (ARSIs, chemo, PD-1 inhibitors, etc.). This is a possible way in. And these drugs aren't unnecessary either. They add value. I use ARSIs, ADT, PARP inhibitors, etc.