Anyone have mBAT experience? - Advanced Prostate...

Advanced Prostate Cancer

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Anyone have mBAT experience?

Djangler profile image
35 Replies

I'm mCRPC with node involvement, extensive bone mets, and recent liver mets.

I was diagnosed with mHSPC (bone and node) in June 2021, I progressed on Lupron/Zytiga with 6 cycles of docetaxel (PEACE1 triple therapy protocol) in October 2022. I dId Provenge at time of progression and am currently on olaparib/Lupron/Zometa. I'm responding well but I'm curious about BAT and in particular Dr. Morgentaler's mBAT (four 2-week cycles of testosterone followed by four weeks of Xtandi). Has anyone here had experience with this protocol? Is it something I should consider now, or should I wait for progression on olaparib?

35 Replies
Tall_Allen profile image
Tall_Allen

BAT is experimental and can be quite dangerous and is never given to symptomatic patients.

There was a trial combining BAT and olaparib in 30 men who had progressed on Zytiga or Xtandi. Half had DNA damage repair defects.

• ¾ had at least some PSA reduction

• 47% had a PSA reduction ≥ 50% (44% if 2 who dropped out for progression are added)

• 23% had a 12-wk PSA increase ≥50% (28% if 2 who dropped out for progression are added)

• Median progression-free survival was 14.8 months if they were mutation-free vs. 7.5 months if they had the defects.

• 2 patients had a complete PSA response

• 5 of 8 90+% responders were free of DNA damage repair defects

• 3 of 6 90+% progressors had DNA damage repair defects

• 5 patients had serious (grade ≥ 3) toxicity, including one death

The cause of responder/non-responder differences remains elusive.

urotoday.com/conference-hig...

Djangler profile image
Djangler in reply to Tall_Allen

Thanks TA. I've read a good bit of the literature on BAT. I understand the dearth of RCT data on this treatment. I'm not symptomatic, and in fact, I feel quite well and have tolerated my other treatments with minimal AE. My MO is willing to consider BAT as part of my treatment plan, but we haven't discussed exactly where it fits.

I've requested a consult with a doctor he knows at Johns Hopkins. I want to understand the risk/benefit. In particular, I haven't seen a lot of discussion about what happens to the roughly 1/3 of patients that discontinue BAT due to poor response (exponential PSA rise). Would trying this cut months off my already short OS prognosis?

I have BRCA2 and TP53 variants, but not RB1 or PTEN. There's some indication that these variants are markers for improved response, but as you say, this is far from established. There's also some evidence that BAT increases successful rechallenge on NHT - again, the evidence is more than anecdotal, but less than conclusive. One thing to consider, mCRPC with visceral mets is already quite dangerous - in fact, it's about as close to guaranteed fatal as you can get. If BAT buys me some extra good months I'm willing to consider it, but I want to understand the risks before I decide.

Tall_Allen profile image
Tall_Allen in reply to Djangler

That's a very rational response.

noahware profile image
noahware in reply to Djangler

Regarding the roughly 1/3 of patients that discontinue BAT due to poor response (exponential PSA rise): Denmeade has noted that the high-T itself can promote an increase in PSA without that increase necessarily indicating a PC progression as severe as suspected... possibly, in some men, PSA will rise without ANY radiographic indication of worsening disease.

You are absolutely right to question the impact on OS... that is what counts, after all, and not the PSA number. I also hope to pursue BAT as a "roll of the dice" because at the very least, even if the high-T fails to temporarily slow progression or even if it promotes progression, I expect the QoL boost may be worth it. For some, losing a few months of OS may be a fair trade-off for gaining some higher QoL as one approached the end of life. (We are incurable, after all.)

I tend to see Pluvicto as being great for about 1/3 of men, inconsequential for 1/3, and perhaps ultimately harmful for 1/3. I tend to think of BAT as having a similar distribution, in very rough terms. One difference? While it appears Pluvicto helped me to become quite anemic, I see a possibility of BAT helping me become LESS anemic (since high-T is known to help some men in that regard).

Another difference of course is that one therapy costs $40k per dose and the other costs just $40 per dose, lol.

cesces profile image
cesces in reply to Djangler

I would get multiple second opinions from docs that actually practice bat.

I would include Dr. Sartor at Tulane.

Yingsang profile image
Yingsang in reply to Djangler

The Dr. Morgantaler last in-house clinical trial he ran was most interesting. I do not know how the men selected were chosen. Dr. Morgantaler ran this in-house trial out of His Boston's Men's Health Clinic. I understand and I may be wrong, that he chose men who had very little time left, and that some were already in discussions with their Local Hospice. I heard they were looking at 6 months to 12 months left. But who can predict? They all had to sign waivers that the procedure had a high probability of causing further Physical harm and Death.

As to the trial that I do not believe he published, there were 23 men selected. 2 died of Heart Attacks, 3 dropped out due to side effects they could not stand, and 18 were still alive 4 years later. They may have passed by now, but those 18 got a lot of days of life.

And you are right Dr. Morgantaler used 400 mg injections every 2 weeks for 2 months and then stopped and in the 3rd month he used full dose Xtandi. And then repeated the 90 cycle. I believe he reached levels of from 2000 ng/dl to 2,200 of Total Testosterone.

It is interesting to note that soon after Dr. Denmeade in a new trial, who's name I do not remember, has decided he had to go longer than one month with Testosterone Cyprionate, to 2 months, and that he will use Xtandi, as his ADT.

I have been following this as a Girlfriend who Posts here, got a connection with a Doctor in I think Emory, and is doing some form of BAT.

As a side note: You can contact Dr. Morgantaler even though he is retired and he does consults. I do not know how to contact him, and I hear that his consults are very expensive.

Djangler profile image
Djangler in reply to Yingsang

Thanks for the info. Interesting that Dr. Denmeade is shifting to 2 mo. on 1 mo. off with enzalutamide ADT. My MO is open to BAT, but I don't know if he's onboard for this newer protocol. My current prognosis is <12 months so maybe he'll let me drive on this decision.

Djangler profile image
Djangler in reply to Yingsang

My MO referred me to Dr. Paller at JH to discuss BAT. She didn't have an open slot that worked for me so I'll be meeting with Dr. Denmeade. I'll ask him about this.

lowT163 profile image
lowT163 in reply to Tall_Allen

Boy that would be a great treatment. I asked my doctor about high testosterone as a treatment and I’m glad we were in a chat instead of a visit. I swear I saw a smile in his hell no reply to me. However he has indicated in the past that low testosterone may be related to prostate cancer. Obviously no clear answers but he has pushed me to get mine above 300 and my tumor was way out of the bag and may have invaded my rectum.

I’m wondering the difference between testosterone tests. My normal testosterone is 264 this month and I had a free testosterone test for the first time of 2.3. 264 kind of up in the green and 2.3 way down. How are they related?

Yingsang profile image
Yingsang in reply to lowT163

Almost none of your t was available and probably bound to your SHBG. I think the minimum in the range of Free Testosterone is 47, and you are showing 2.3. You probably have more active Estrogen than Testosterone.

lowT163 profile image
lowT163 in reply to Yingsang

so I wonder where the science is on the guys hoping to get testosterone back enough to have some energy yet not wake the cancer up.

cesces profile image
cesces in reply to Tall_Allen

All very interesting.

I hope you do a page on your blog on this subject when the fog of war clears.

tango65 profile image
tango65

This is info from the people who created BAT.

urotoday.com/video-lectures...

It has its limitations and require a correct selection of the patients, but it can be done out of a study,.

Dr. Denmeade:

"Again, based on enough experience, now we've treated several hundred patients that I feel like those patients who have access to this, who want to try it. But again, making sure their physicians understand these issues about pain and other limitations of the treatment, like the right stage of the disease, et cetera.

So yeah, it's an easy thing to do. The testosterone is very inexpensive. It probably costs $20 a shot, so it's very inexpensive. So patients, even if their insurance won't pay for it, can try it. And sometimes patients write us back and tell us they've had great experience, and that's hope. For now though, I've been trying to do the best I can to educate everybody about making sure it's the right group, the right timing, and the right symptom complex.

Clearly, this is a therapy for a certain stage of the disease. So, patients who have not had any hormonal treatment, probably the opposite would happen. If we gave testosterone, we might even make it worse. So, certainly in patients who haven't had local treatment for prostate cancer, it's not the right thing, or who haven't had hormonal treatment yet, hormone lowering treatment. We think there's the stage of the disease where this is appropriate, and those are the patients we focused on in all of our trials.

We've also found patients who have a lot of symptoms from prostate cancer, particularly pain, this is probably not a good idea. Because, when we first give the testosterone, people can have what we call a flare where the disease could not necessarily grow but make factors that can make pain worse. So, we found that in guys who have pain already, few guys that we treated, the pain gets a lot worse. People that don't have any pain seem to do fine, and that's the majority of the patients we've treated. But clearly, I get asked a lot of questions from people around the world, that's really the place that this is for patients who've become resistant to their primary hormone therapy, their second hormone therapy that we use, that's the group we look at."

Djangler profile image
Djangler in reply to tango65

Thanks, I watched that the other day. I'll be talking with a different doc at JH to see if BAT is appropriate in my specific case. The reason I posted this question was to see if anyone has experience with Dr. Morgentaler's mBAT protocol.

tango65 profile image
tango65 in reply to Djangler

BAT may be appropriated in your situation since the cancer has a P53 mutation. and you do not have symptomatic PC.

PCs with P53 mutation seem to be the ones with the best response to BAT.

I wonder if you have data from Dr Morgenteler about the results with his mBAT protocol.

I could not find any RCT with his therapy.

Djangler profile image
Djangler in reply to tango65

Yes. The P53 is one of two things that excite me about BAT. As far as I know, it's the only treatment where P53 is an asset instead of a liability. The other thing is resensitivation to NHT drugs. I progressed on abiraterone, but I'm hoping for response to enzalutamide if I do BAT.Of course, it also might be nice to have some testosterone back in my system for a while. ADT hasn't been awful, but there are things I miss from before 😉.

As far as I know, Dr. Morgentaler's data is entirely from case studies of his patients. No trials that I'm aware of.

smurtaw profile image
smurtaw in reply to Djangler

I am using a similar program but it is not identical.

noahware profile image
noahware

I believe Dr. M's mBAT patients were just a handful of men representing something like a small-group case study rather than anything like an RCT. Because he is retired, I suspect there are very few men who have tried his protocol, and even fewer docs willing to prescribe it since it does not have the RCT protocols of the Johns Hopkins trials.

As for trying BAT sooner vs. later, it is important to consider that if you progress to the point of having painful mets then you run the risk of being denied that treatment, since Denmeade has mentioned he excludes those men (as well as those who are still hormone sensitive).

On the other hand, who wants to give up a therapy that still appears to be working well?

smurtaw profile image
smurtaw in reply to noahware

When I started on my modified BAT program, I put a target of 6-12 months before my PSA and scans indicated that I had to move on. Happily, I underestimated what a modified BAT program was capable of doing. I could argue that I have been following some form of BAT for 4 years. To say the least my prognosis 4 years ago wasn't good.

My MO is very pleased with my results and tells me not to stop. During our last appointment, she discussed using me for a case study.

noahware profile image
noahware in reply to smurtaw

That's great. You are certainly an outlier as far as those attempting BAT, by not being either in a trial or following trial protocols, but I think your success is inspiring for those considering any form of BAT whether self-designed/directed or not. I think I have found an MO willing to go the Denmeade route with me, and it's pretty exciting. (Of course, so was the chance to be in a Lu177 trial, which did not work out so well for me... but ya gotta keep rolling those dice.)

I also think it's great that you gave yourself 6+ months to gauge progress. I don't want to dismiss the so-called "dangers" of BAT, but for others who are more cautious doesn't it seem simple enough to just stop it after several months if it appears to not be working? Even if there is PC progression in those months I have a hard time believing there would be a huge impact on OS. One also gets a QoL boost and a possibility of being resensitized to AR agents. A risk worth taking, in my view.

In my reply to Djangler I was referring to "mBAT" in the context of Morgentaler's version of it (let's call that "MmBAT"). Yours is a bit different, and it would be interesting to see a compilation and comparison of your case study and Morgentaler's case studies and any other individual attempts that differ from "conventional" BAT. A new project for you!

smurtaw profile image
smurtaw in reply to noahware

Thanks. And congrats on having your MO do the Denmeade BAT program.

A couple of things to consider asking your MO/Denmeade:

1. Could you use a low dose of E2 on the low T phase (if needed)?

2. Could you do 1-2 weeks of Xtandi on every low T phase?

3. Could you extend the cycle to 6-8 weeks?

I completely agree with the low risk of BAT. If it starts going south, you could simply stop. Denmeade doesn't think that you are going to see a major detriment in just a few months. My MO and I agree.

For some guys, it is contraindicated. So it is prudent to research and then talk to your MO or a knowledgeable BAT doc.

About the modified BAT programs, a few guys are starting testosterone propionate BAT (or pBAT). I'm going to be in close touch with each of them. The more data the better for all of us.

Farmhand profile image
Farmhand in reply to smurtaw

If you extend the cycle to every 6 to 8 weeks, How often exactly do you receive the 400 mg testosterone cypionate injection?

smurtaw profile image
smurtaw in reply to Farmhand

If you use cypionate, you could do just one 400 mg injection. Or you could do 2 injections - day 1 and 14, and then Xtandi on days 21-35 and then let one month go by to wash out the Xtandi.

If you use propionate, it opens up lots of possibilities. But I haven't encountered an MO who will use a U.S. compounding pharmacy for propionate. Most of them do not even know that you can get it here.

If you're interested in BAT, I could post exactly what you would expect from 2 months with 1 cypionate injection - or 10 weeks and two cyp injections with Xtandi during ADT.

Farmhand profile image
Farmhand in reply to smurtaw

That would be great if you could do that. Just got back from a trip to Minneapolis to consult with Dr. Emmanuel Antonarakis, Luckily I appear to be in the “sweet spot” for starting BAT. Doing it off study with PP overseeing, So there is some room for improvisation. I have BRCA2 germline mutation, asymptomatic, PSA 2.1, just becoming resistant to second line Zytiga. On Orgovyx.

smurtaw profile image
smurtaw in reply to Farmhand

This is the two injections with Xtandi. 400 mg cypionate day 1 and 31. Xtandi days 57-70. 84-day cycle.

mmBAT
smurtaw profile image
smurtaw in reply to Farmhand

60-day cycle. Cyp only. 400 mg on day 1.

2 month BAT
Jancapper profile image
Jancapper

For a nice current summary, including results from 3 trials, see this article authored by Dr. Denmeade, Et Al.

onlinelibrary.wiley.com/doi...

smurtaw profile image
smurtaw

I use a modified BAT program. 1-month high testosterone using testosterone propionate followed by two weeks of Xtandi or Casodex and sometimes followed by two weeks of Zytiga. I wait until my PSA dictates and repeat the cycle.

Denmeade recently said that he wasn't using testosterone propionate because it wasn't available at any U.S. compounding pharmacies - I sent him an e-mail to let him know that empower can compound it in Texas.

mBAT is superior to the simple programs that have been used in trials. Some of the trials in recruitment are catching up.

These are two recent combination therapy clinical trials with excellent results.

Concurrent administration of bipolar androgen therapy (BAT) and nivolumab in men with metastatic castration-resistant prostate cancer (mCRPC). | Journal of Clinical Oncology

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

ESMO 2021: Bipolar Androgen Therapy (BAT) Plus Olaparib in Men With Metastatic Castration-Resistant Prostate Cancer

urotoday.com/conference-hig...

I expect that STEP-UP will show better results than previous trials:

clinicaltrials.gov/ct2/show...

BAT appears to increase sensitivity or restore sensitivity to Xtandi (and perhaps other drugs that block the ARs such as bicalutamide). After conclusion of BAT, certain immune pathways are enhanced, and immunotherapy responses are improved.

In the RESTORE clinical trial, men with CRPC progressing on either Xtandi or Zytiga were treated with BAT. Once BAT stopped working, the patients received the same drug that failed prior to BAT (Xtandi or Zytiga). Of the patients who progressed on Xtandi and then proceeded to BAT and were rechallenged with Xtandi, 70% had a PSA response to rechallenge with Xtandi. For the patients who progressed on Zytiga and then proceeded to BAT and then were rechallenged with Zytiga, the PSA response was much lower at 17%.

The TRANSFORMER clinical trial, men with CRPC progressing on Zytiga were treated with either BAT or Xtandi. After failure of the starting therapy (Xtandi or BAT) patients were given the option to cross over to the opposite therapy. Thus, men on BAT could go on to get Xtandi and vice versa. For the patients who received BAT first and then received Xtandi, PSA went down by at least 50% in 77.8% of the subjects. For men who received Xtandi directly after Zytiga, the PSA response was seen in 25% of men.

In one arm of the RESTORE clinical trial, men with CRPC who had never received Zytiga or Xtandi were treated with BAT. The PSA response to BAT was low in this group at about 15%. However, some patients in this study went on to receive Xtandi or Zytiga after BAT. In these patients, 95% of the men had more than a 50% decrease in PSA, 85% of the patients had more than a 90% decrease in PSA, and 50% had PSA levels that became undetectable. The duration of response to Xtandi or Zytiga after BAT in this study was over 2 years. As a comparison, in the studies that led to the FDA approval of Xtandi or Zytiga as first‐line therapy for men with castration‐resistant prostate cancer, the PSA response was 78% and 62%, respectively and the duration of PSA response in both studies was 11 months.

Reading through the results of the very basic high testosterone/medium-low testosterone program that has been used in trials, it is obvious to me that if BAT is used properly, is an excellent option for many of us.

Some of us might have the luxury of waiting to see if modified BAT programs are admitted to the SOC domain. I did not feel that I had this luxury. So I have been using my own modified BAT scheme for the last 18 months with excellent results. TMB has decreased. PSA has decreased. No signs of cancer on F18- PSMA-PET scan. I am still HSPC 4 1/2 years post-diagnosis.

If you are interested in more info and references and a list of trials, PM me.

smurtaw profile image
smurtaw

If I might suggest a modification to mBAT, I would let Xtandi washout before starting the next cycle.

Chart is attached with notes.

modified mBAT
Djangler profile image
Djangler in reply to smurtaw

Interesting. I assume these charts are from a model you've developed rather than experimental data. If you're willing to share, I wouldn't mind seeing your source code. I'm assuming this includes continuous ADT along with testosterone/Xtandi.

I believe Dr. M's protocol is testosterone on 1, 14, 28, 42 and Xtandi on 56-90. He saw a slowly rising PSA nadir on each cycle. Do you see that with your protocol?

Quick question, does your insurance cover Xtandi used in tbis non-SoC treatment plan? I got a shock last year when I found out my prescription plan only covers olaparib at 70%. Fortunately there's a manageable out-of-pocket cap.

smurtaw profile image
smurtaw in reply to Djangler

They are from my model. I use the theoretical and measured half-life and DHT blocking of various drugs and the steady state and concentration increase and decreases. I also verified the testosterone levels with the results of 32 blood test results over the last 4 years. Rather accurate for me. The actual to predicted error is typically 1% to 5%. A few months ago my MO asked me to measure my tT. I told her that I was waiting for test results and that my tT was about 1850 ng/dl. Then I got the measurement and sent it to her (I think it was 1854 ng/dl).

It would take days to pull all of the formulas and references. I'm certain that I would miss some since I started this work 4 years ago.

Does he inject T 4 times per cycle? What dose does he use? Cypionate? 160 mg of Xtandi? Is it the escalating dose program? He posted many different ones (good for him - as we learn we must adapt).

The results are better. 3 out of 4 T injections lead to SPT levels if the injections are 300+ mg. I like the escalating dose program. He uses 200 mg for 5 cycles (not sure if these are 12-week cycles or if they are 2-week injection cycles). Then he goes to 400 mg. The 200 mg is weak and won't promote some of the mechanisms of BAT. But it is nice to enter slowly to judge pain and see if progression is fast.

I see a slowly decreasing PSA nadir. Lower lows and higher highs. My nadir was 0.1 and has dropped to 0.02. In the future I am going to target 0.05+-0.02. I toyed with targeting <0.01 but I think I might be playing with extinction of a cancer cell type. That could be dangerous since my goal is to keep it under control.

Farmhand profile image
Farmhand in reply to smurtaw

Add targeted alkylating glycolysis inhibitor to the mix to block upregulation of highly glycolytic androgen independent mutations?

smurtaw profile image
smurtaw in reply to Djangler

My insurance covers Xtandi. With manufacturer assistance it is 100% covered.

My BAT program and the other therapies that I have used are not SOC so they "don't exist". It's kind of like taking supplements.

I actually qualify for PSMA-PET scans because I can show high PSA from my high T phases. And lots of other cancer meds. My insurance is very stingy so my MO and I use what we can to actually get some kind of coverage...

smurtaw profile image
smurtaw

non-modified mBAT

mBAT
smurtaw profile image
smurtaw

"Traditional" BAT. One 400 mg cypionate injection IM. This does not even come close to an ADT androgenic testosterone level.

BAT

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