Potential reversal of CRPC. - Advanced Prostate...

Advanced Prostate Cancer

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Potential reversal of CRPC.

smurtaw profile image

Supraphysiological Testosterone Therapy as Treatment for Castration-Resistant Prostate Cancer - PMC

ncbi.nlm.nih.gov/pmc/articl...

CRPC and NEPC development and potential reversal: Loss and revival of androgen receptor signaling in advanced prostate cancer | Oncogene

nature.com/articles/s41388-...

59 Replies

🐽🐽🐽🐽

When pigs fly.

Just saw a flock today!

My MO is at a loss to explain why my TMB is decreasing, I was lymph node positive yet on PSMA-PET scans I am now "clear", my bone density is increasing (my MO didn't talk about this, but my PCP did not believe it), and why my PSA is going to zero. Could be luck. Could be diet or exercise or maybe the air quality in my city or fluoride in the water. Or maybe it's all the flocks of pigs flying by.

smurtaw wrote -- " .... Or maybe it's all the flocks of pigs flying by."

DANG, sure could have used a FLYING PIG 6 weeks ago and maybe I wouldn't have a fractured Tibia from that WILD HOG head butting my left leg while I was simply riding past it on my bicycle. and I don't even eat PORK 😀

Maybe he was offended that you don't dine on pig carcass.

Not so sure the genie can be put back into the bottle.

smurtaw profile image
smurtaw in reply to EdBacon

I'm not certain that everyone is going to be able to put it back. But if we don't try, .... you know the rest.

EdBacon profile image
EdBacon in reply to smurtaw

I think every plausible treatment option needs to be looked at. Even it just buys more time it's worth it. My doctor said a 30% response rate is a "big deal" in the cancer world.

smurtaw profile image
smurtaw in reply to EdBacon

So far it looks like resensitzation rates are better than that. Another trial is being run.

smurtaw profile image
smurtaw in reply to EdBacon

One of the things that I have gained is at least 3 years of continued hormone sensitivity. Even if it fails, it's a win.

EdBacon profile image
EdBacon in reply to smurtaw

So you aren't castrate resistant, right?

smurtaw profile image
smurtaw in reply to EdBacon

No.

aixen1990 profile image
aixen1990 in reply to smurtaw

but you were, right?

smurtaw profile image
smurtaw in reply to aixen1990

Maybe. Time will tell. But since only two people are doing the T-prop and NPP we can't really determine.

smurtaw profile image
smurtaw in reply to aixen1990

No. I am doing PropBAT in hopes of never becoming CRPC.

Thanks for postings on BAT. You appear to have researched this subject a good bit.

All of the research to date has been performed on men who have developed some form of castrate resistance. After reading your bio, I understand you are not castrate resistant. My question is, how do you apply the lessons learned to your situation given the mechanism of BAT is to overwhelm the pca by bouncing between periods of High/Low T levels?. Are you proposing this same High/Low bouncing will prevent castrate resistance and thereby allowing you to remain on this for an indefinite period of time?

That is my hope. We have some promising RCT data (resensitization to ARSIs).

My thought is that AR upregulation/mutation is not a mass digital action. You don't go from hormone sensitive to NEPC or fully castrate resistant overnight.

So, what I am hoping is that as the ADT phase of BAT goes on, some cancer cells will start to upregulate/mutate their ARs. As they chug along, the high T phase of BAT comes by and the extra ARs and mutated ARs are a liability. "Food" is plentiful. So they will start to downregulate in order to remain competitive. But then along comes ADT again. So, upregulate, then high T, downregulate, ....

If I am right then my PCa might become a manageable disease like diabetes. Eventually it overwhelms fading systems but a long life precedes that.

If I am wrong, I bought myself 2 years doing supraphysiological T and at least 1 more year doing BAT.

Or you die of a massive heart attack....but I get it...I'm in the similar situation...Age 56 and basically a terminal disease...if not tomorrow..someday.

ADT, while bad, is not the worst thing in life...I'm actually living the best of my life right now....I'm keeping an eye on the BAT treatments...and reading your posts...but sitting on the sidelines for now. I recently learned I have ATM mutation from my Foundation One test. I'm actively researching what this means treatment-wise...not much in my opinion at the moment (Lynparza) but may be more significant if the new PARP + ATR inhibitor trials yield good results. The germ-line results should be in in 2 weeks but those results impact my daughter and family more that me.

Yeah, it's a game. Play this risk vs. another one. Risk of sarcopenia and CRPC vs. risk of cardiac arrest.

I'm glad you're doing well on ADT. We all handle it differently and some guys do just fine. When I tried SOC ADT I lasted all of 2 weeks. The mental stuff got to me.

spencoid2 profile image
spencoid2 in reply to smurtaw

The mental stuff disappeared for me. Could not remember anything, could not program computer and the spaced out feeling had me feeling unsafe operating machinery. Tried various psycho drugs and nothing helped and then voila, brain fog was gone. Might want to give it more time if you can spend a few months as a space case. I really value my mental clarity and to me the brain fog was devastating. Was ready to give up ADT.

JPOM profile image
JPOM in reply to spencoid2

Try huperzine A - got my brain outta hock, way better memory, access to vocabulary, energized my imagination, dream like crazy all night. great sh*t!! PS this is the only brand that works. doublewoodsupplements.com/p...

smurtaw profile image
smurtaw in reply to spencoid2

Mine was more paranoia and delusions. Not good for a marriage. I swore to my wife that I would never do that again.

spencoid2 profile image
spencoid2 in reply to smurtaw

I was not paranoid and deluded but definitely lost patience more easily and still probably do.

smurtaw profile image
smurtaw in reply to spencoid2

I went through stages during my descent into madness. I started out by just getting irritable and losing patience. In my case it got worse.

I was full on delusional, paranoid, depressed, and lying. I realized it after almost beating up a guy in a parking lot for having the gall of delaying me for 5 seconds and later in the day asking my wife for a divorce (I still don't know why I did that).

Anyway, after realizing that I was going crazy, I shot up with testosterone. My mind cleared within hours and then the task of patching things up with my wife and friends began.

Some guys handle ADT great; I wish that was my case but as it is, SOC-ADT is off of the table. I need to replace some estrogen, or I go crazy.

Mrtroxely profile image
Mrtroxely in reply to smurtaw

that an intresting path your on.

Ill keep following.......quietly, silently, looking, peeping......

jac_j_sp profile image
jac_j_sp in reply to smurtaw

Wow. I experience symptoms a bit like you. Im pretty ok most of the time in terms of patience and mental stability. When I not, Im very aggressive towards people who I deem as not on my side. I have no fear, which may get me in trouble one day.

I also asked my wife for a divorce recently because I believed she was not supportive enough and didnt take my PC seriously enough.

I think the time has come. PSMA-Pet then BAT experiment.

Thanks for your honesty.

smurtaw profile image
smurtaw in reply to jac_j_sp

I try to be as open and honest as I can. We can learn from others. I'm going to tell my wife right now that I am not alone with the hostility/no fear/divorce thing.

Spyder54 profile image
Spyder54 in reply to smurtaw

Appreciate your Honesty Smurtaw. My wife says my patience is gone. Said she married the most patient Man. Now ADT has changed that. I am on the verge of mBAT. Guys that were on it last year disappear off this site, and we can no longer follow their N=1. Are they gone for health reasons? I would think their spouse would let us know. At one point I knew 8-10 guys on diff forms of BAT. Now I know of 2, maybe 3. For all we know, the ever changing SOC Landscape may be heading toward BAT? Are there powerful groups that do not want that to happen? Possible. Mike

smurtaw profile image
smurtaw in reply to Spyder54

Maybe there are groups that don't want that to happen. I can think of some individuals who are stuck in the status quo and don't embrace change.

But it is up to us. That's one thing I love about our options. We are free to do as we want. If we do something stupid... well, we suffer. But if we do something great, we reap the benefits and nobody can take them away from us.

PROP-BAT has been nothing short of amazing for me. I'm in far better shape than I was before PCa. Less fat, more muscle, finally out of the osteopenia zone and not just age adjusted - real bone density increase! Cholesterol lower than it has ever been (statins). If I had a wish I would wish that this would go on until I die. I'm about to workout - second workout today. Then tonight I'll do a third. I did not have the energy and desire to do this 5 years ago. My wife is very "satisfied" if you know what I mean.

And yes, I'm doing some bragging. 3 short years ago I was 135 lbs and growing little boobies. Now I'm 215 and the only sign of a big chest are my pectorals.

But in a month I'll be on the low T phase of PROP-BAT. I'll struggle as usual and my wife will have to wait to be "satisfied".

There was one clinical trial by Schweitzer at Washington on CS men. Conclusion was it was not harmful.

smurtaw profile image
smurtaw in reply to cigafred

BATMAN

Found this interesting talk on BAT for anyone who wants to listen to it. It's from May of this year so it's fairly recent. One of the interesting findings discussed is BRCA, ATM and P53 mutations may be more sensitive to BAT.

urotoday.com/video-lectures...

smurtaw profile image
smurtaw in reply to EdBacon

Some good info in it.

KocoPr profile image
KocoPr in reply to smurtaw

good video, but they still are not recommended for Castrate sensitive, Also interesting about the success with double strand break mutations, ,P53 and combining with a radiation therapy for those 35% with those mutations.

They are making progress but it is slow going. They need to study the modified BAT you do.

smurtaw profile image
smurtaw in reply to KocoPr

I would like to find a study using propionate.

BATMAN was done on HSPC men. Good results. But again, not with propionate.

smurtaw profile image
smurtaw in reply to KocoPr

Interesting that Myc was inhibited. If this is correct, we can try to inhibit Myc and perhaps improve the effect.

ARSIs inhibit Myc, R1881 (similar to nandrolone) inhibits Myc. Curcumin, EGCG, vitamin D3, lycopene, and aspirin might inhibit Myc.

This is all very speculative.

JPOM profile image
JPOM in reply to smurtaw

Try huperzine A - doublewoodsupplements.com/p...

Acetylcholinesterase inhibitor, made in the US of A

V10fanatic profile image
V10fanatic in reply to JPOM

Here's an interesting NIH article on it- ncbi.nlm.nih.gov/pmc/articl...

JPOM profile image
JPOM in reply to V10fanatic

Thanks; high tech article with a bunch of organic chem terms and diagrams that I have long forgotten. Found the relevant statement I needed: "Clinical trials with this AChE inhibitor revealed cognitive and functional impairments at patients with AD, schizophrenia and vascular dementia, and memory improvement of elder people."

I'm in the last category and after $$ wasted on different brands, found the only one that the synthetic form actually works as well as the natural clubmoss capsules. The moss has a long growth cycle and was largely being produced in China, which ran out after word got out. Anywho, thnx again, friend. PS I noticed the article mentioned other substances that are AChE inhibitors. Berberine was high up on a comparative scale (see below) so I paid a sh*t ton for a bottle and after one 500mg dose that almost knocked me out, decided not to even try microdosing.

color chart
JPOM profile image
JPOM in reply to V10fanatic

Here's a more comprehensive chart, listing the plant sources of various AChEIs

lengthy chart
Benkaymel profile image
Benkaymel in reply to EdBacon

I thought the last comments by Professor Antonarakis were useful and very important caveats for many of us considering BAT due to the low (10% ) but real risk of disease flare:

"All of our trials excluded patients who had painful bone metastases. All of our trials excluded people with large osseous lesions in weight-bearing bones or joints like the femur, or lumbar spine. Anything that might increase the risk of an imminence cord compression should be avoided. And in patients who have a bulky primary disease or bulky pelvic lymphadenopathy where a flare might clip one of their ureters, or obstruct their bladder, you may want to think twice.

The ideal patient .... someone ideally who is asymptomatic from a bone pain perspective who is not taking, for sure, narcotic analgesics for bone pain, someone who does not have a bulky primary, and someone who is not at risk of a pathological fracture or a spinal cord compression."

smurtaw profile image
smurtaw in reply to Benkaymel

That is something to think about. Is it better to try PropBAT early to hopefully stave off CRPC? If it is early enough, not many men will be excluded.

Or should we wait until we are CRPC and might be excluded from trying it?

What I have gleaned from comments made by Denmeade et. al. is that they felt that it was a simpler road to become SOC if they showed CRPC treatment efficacy. Much higher bar if they tried to show superiority or non-inferiority for HSPC.

The other thing that stood out in an interview with Denmeade is that he wants to use compounded creams so that a true castrate level can be obtained. This tells me that he knows that cypionate isn't optimum. However, it does not tell me why he prefers creams instead of propionate.

Interesting article. I was especially interested in the following statement in your first article:

“In addition, intermittent AA therapy has been recently shown to delay the development of resistance from 16.5 (continuous treatment) to 27 months (45). Whether the intermittent therapy diversifies the residual tumor clones or re-sensitize the residual clones to a therapy that formerly failed remains scientifically and clinically important.”

I was unaware that intermittent therapy had ever been shown to “delay the development of resistance”. I’d thought only that there had been shown no substantive difference between continuous and intermittent therapy per the studies to date . Does anyone know what recent study showed this to be? A lot of us on intermittent therapy or considering it would find that study quite useful.

Tall Allen any thoughts?

Schwah

smurtaw profile image
smurtaw in reply to Schwah

Intermittent Zytgia therapy isn't the same as BAT. I don't think that intermittent AA therapy is the key to CRPC reversal.

PropBAT is repeated cycles of T>1500 ng/dl followed by T1500 ng/dl followed by slow decays down to T = 200 ng/dl.

CypBAT has been shown in RCTs to resensitize 60%+ of CPRC men to Xtandi. Note that this is with cypionate, so they never go to castrate levels of T. A follow-up RCT is being conducted to see if this can be done multiple times.

Just saw this on GrandRounds:

Maintenance of androgen deprivation therapy or testosterone supplementation in the management of castration-resistant prostate cancer: that is the question.

urotoday.com/recent-abstrac...

I'm hoping I'm not in the 10% who do really bad on BAT. Not real promising so far. 8 mo. of treatments with PSA climbing 90 % per month.... Started BAT and feel good. One month in and PSA didn't go up 90 % this time... up another jump -----3 3/4 times what it was a month ago... Second injection tomorrow and MO appt on Tuesday. One more month and then we shall see..

smurtaw profile image
smurtaw in reply to Shooter1

Did the 8 months of treatments include BAT?

Danmeade says that barring pain, men should continue BAT for 3 months and then assess.

I hope that conventional BAT works out. If it doesn't maybe your MO would consider propionate? I think it is head and shoulders better for BAT. No comparison. Real castrate vs. lowish T levels.

Shooter1 profile image
Shooter1 in reply to smurtaw

Scans scheduled for 3 month pt... My 8 months.--- PSADT was down to 12 days.. Radiation followed by Provenge and then radiation again followed by Xofigo. Three month and 4 new mets later Ra-223 was stopped. Stopped xtandi which I had been on for about 4 years. Then started BAT after clearout time for xtandi.... So no, 8 mo. was before BAT.. Hoping for better tests of PSA after 2nd dose...

smurtaw profile image
smurtaw in reply to Shooter1

I hope you get better results. High testosterone is going to stimulate PSA production. So if you measure PSA at the start of the cycle it is going to be high. What they usually do during BAT is measure at the end of each cycle to see how things are going.

Shooter1 profile image
Shooter1 in reply to smurtaw

The 80.90 was after the first 28 day cycle. I expected a rise, but not this big... Next time should tell a fuller story....

smurtaw profile image
smurtaw in reply to Shooter1

Was that at the end of the cycle?

Shooter1 profile image
Shooter1 in reply to smurtaw

Yes. At the end of first cycle. 21.4 three days before first injection of T.

smurtaw profile image
smurtaw in reply to Shooter1

I guess give it one more month but that doesn't sound good.

Or you could bail out now and let your T go to zero. Then measure your PSA and do scans if you can. 28 day cypionate BAT isn't going to get you down even close to castrate. But if you wait 56 days your T should be around 20 ng/dl. If you wait 84 days it should be around 2 ng/dl.

If your PSA and scans look good after 56 or 84 days perhaps your doctors would consider doing BAT but a longer timeframe?

Best case they would look into propionate. But that might be too much of a paradigm shift for them to handle.

Spyder54 profile image
Spyder54 in reply to smurtaw

Mateo is doing 3 months High T, one month low, but phases at end of high T, into T Cream on forearms which has a much shorter life than T Cypionate and allows a return to low PSA much quicker.

smurtaw profile image
smurtaw in reply to Spyder54

I used cream/gel for a while. I can get my T up nicely. But it seems too variable. On most tests I am over 1500 but twice I was less than 1000. Gels/creams are much better than cypionate.

So now I use propionate. Short half-life. Not quite as short as gels/creams but close. And I can easily get my T > 2000 and have never had a disappointing lab.

His timeframe is similar to mine. I use PSA targets to determine the exact time. Typical is 4 months high T and 2 months low.

If you let enough time go by, cyp will eventually clear out and you'll go castrate. During a one month cycle as is conventionally done, your serum T will only go to about 200.

Cypionate testosterone vs time
smurtaw profile image
smurtaw in reply to Spyder54

Propionate

Propionate testosterone vs time
smurtaw profile image
smurtaw in reply to Spyder54

This is what I do

actual propionate testosterone vs time
MyDad76 profile image
MyDad76 in reply to Shooter1

Doug, I just wanted to say that I have been thinking of you and I hope new treatment will work!

Spyder54 profile image
Spyder54 in reply to Shooter1

best of luck for trying Shooter. Ive been following and know you are in later innings. Gosh I hope BAT can turn back the clock. Mike

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