intermittent anti androgen monotheray... - Advanced Prostate...

Advanced Prostate Cancer

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intermittent anti androgen monotheray and bipolar androgen therapy

rococo profile image
33 Replies

casodex mono therapy raised T to 1000 and going off cycle exposing naked pc to high T would be a mild form of BAT. MAYBE EVEN MORE WITH NEW AA. Has anyone thought of this interesting possibility. I have done this once for a 2-3yr period of 23 yrs of HT

33 Replies
Tall_Allen profile image
Tall_Allen

Because of negative feedback, Casodex will only increase T to a limited extent before your testes stop making T.

cesces profile image
cesces

"mild form of BAT"

Mild form of BAT apparently doesn't work

It has to be extreme levels of Testosterone apparently.

Merely elevated levels of Testosterone is likely the worst of both worlds.

The only thing worse is do it yourself BAT therapy. Nothing good can come from that.

You really need a Doc with hands on BAT experience.

Ramp7 profile image
Ramp7 in reply to cesces

I think that is the tricky part. Haven't explored it completely but how many MO's out there doing BAT?

cesces profile image
cesces in reply to Ramp7

Npt so many. You want a doc that participated in denmeades bat research

Off the top of my head there is Sartor at Tulane. There are others mentioned in these forums.

cigafred profile image
cigafred in reply to cesces

Including Antonarkis in Minnesota and Schweizer in Washington State.

cesces profile image
cesces

"casodex mono therapy raised T to 1000"

Dumb question: I thought you used casodex to lower testosterone levels. Not increase them.

noahware profile image
noahware in reply to cesces

Casodex works on the androgen receptor, not on reducing T itself. While it is an AR antagonist, the serum levels of both T and E2 rise. (On 150mg monotherapy, my T level went to about 1500, as PSA dropped from over 30 to under 5.)

While the higher T does not impact PC progression, since AR is blocked, the higher E2 level DOES impact growth of breast tissue!

cesanon profile image
cesanon in reply to noahware

Ahhh just what I need. Bigger man boos. LOL

noahware profile image
noahware in reply to cesanon

Yeah, and to make it worse, my left got a little bigger than the right!

MateoBeach profile image
MateoBeach

rocooco, I have been considering a closely related question. I am on modified BAT (very high T for 3 months then 1 month on Orgovyx ADT. I am wondering if the ADT phase would be even more effective if I added an anti-androgen. Because:

1) The combination of ADT plus and AART drug has better results for PFS and OS and also delaying castrate resistance in every clinical situation that it has been tested (in RCTs).

2) Blocking androgen receptors further intensifies the selective pressure against AR+, hormone sensitive population.

3) This with ADT promotes AR amplifications and copy number increases which should make the more AR resistant populations even more susceptible to the High Testosterone cycles.

Personally, I cannot use bicalutamide for this since I previously failed while on it and it now feeds rather than blocks my cancer. So I cannot safely go back on it. So it will have to be enzalutamide or darolutamide. Abiraterone is another way to intensify androgen deprivation during the ADT phase. But hard to cycle rapidly with the prednisone requirement.

As has been said, probably just cycling the bicalutamide may not provide high enough testosterone levels to provide true BAT effects. But would be easy for you to measure and see. Would shoot for above 1500 total T, then ideally <20 on the off phase.

noahware profile image
noahware in reply to MateoBeach

Is there any research on resensitizing one's PC to bicalutamide? I recall that niclosimide (?) and/or disulfiram (?) might help make abi effective again after initial failure, and I thought someone posted on a potential agent for doing so with bicalutamide. Ring any bells?

MateoBeach profile image
MateoBeach in reply to noahware

BAT has been shown to resensitize to enzalutamide. So I am just theorizing it might do the same for bicalutamide. Trouble is how to test and confirm that? Would require staying on it and getting serial PSAs. That would interrupt the BAT,so Catch 22.

smurtaw profile image
smurtaw in reply to MateoBeach

I use AA, bicalutamide, and enzalutamide during the ADT phase of BAT. I frequently combine AA with one of the two ARSIs. And there are times when I do not use an ARSI. I always leave a few weeks at the end of each ADT cycle to let AA washout and CYP17 to recover. ARSI washout is even more important, but the washout is faster. My high T phase is 2-3 months in length, so I get by with a 2-week washout at the end of the ADT phase.

The only reason that I use bicalutamide is because it is cheap. I'm going to have my MO switch me from AA to enza and then I'll drop the bical. Because my insurance won't pay for AA and enza at the same time, I'll slowly wean off of AA while monitoring to see if I should pony up the $200 a month for AA ($50 since I would do the food thing).

Xtandi will inhibit the ARs while also upregulating them. The RCT that does high T alternating with ADT/Xtandi should be a good one.

Ramp7 profile image
Ramp7 in reply to smurtaw

I have a dumb question, what is AA?

Miomarito profile image
Miomarito in reply to Ramp7

I love you!👍

MateoBeach profile image
MateoBeach in reply to Miomarito

Thank you for your service. 🫡

Miomarito profile image
Miomarito in reply to MateoBeach

any time

MateoBeach profile image
MateoBeach in reply to Ramp7

Abiraterone acetate = Zytiga plus prednisone.

smurtaw profile image
smurtaw in reply to Ramp7

The only dumb question is the one unasked.

AA is abiraterone acetate = Zytiga.

rococo profile image
rococo

AA ie. the lutamides do not lower T but block it. In response the testes produce more T as mine remained high for years on casodex 700-980 T, Didn’t know at the time, Thought I was a 70yr old buck. Now 84 and still kicking on. Best to all

Benkaymel profile image
Benkaymel in reply to rococo

That makes sense, but I started my treatment in early July on bicalutamide alone for 2 weeks before my first Prostap injection (to prevent tumour flare). The bica continued for 2 more weeks and I had a blood test at the end of the 4 weeks on it (so just 2 weeks into ADT). T was already down to 9.8 which I was told was most likely due to the 4 weeks of bica rather than Prostap since it had only been 2 weeks since my first shot. Now I'm confused! Could ADT bring T down that quickly?

MateoBeach profile image
MateoBeach in reply to Benkaymel

yes it can and evidently did so.

Benkaymel profile image
Benkaymel in reply to MateoBeach

I'm still confused. Tall_Allen said "Because of negative feedback, Casodex will only increase T to a limited extent before your testes stop making T" so how could it increase to over 900 and keep it there for years? Also, my experience implies that ADT in 2 weeks can reduce T by far more than Casodex increases it in 4 weeks.

smurtaw profile image
smurtaw in reply to Benkaymel

Lupron is a GnRH agonist. It's going to yank that hormone signal up and hold it. You will get a T flare until your body realizes that the signal isn't moving. It is the change in the signal that determines T production and not the signal magnitude.

Bicalutamide is going to bind to the ARs. Since they are blocked, they can't receive T. It's about 80% effective (Xtandi, for example, is more like 90-95% effective).

Bicalutamide is frequently used during the first few weeks of Lupron therapy so that the ARs don't accept much of the T from the flare. Some guys, such as I, don't need to use bicalutamide. At this time I'm low volume and a little extra T is going to be fine (more than fine but that's another story).

If you just use bicalutamide your serum T is going to soar. I played around with a bicalutamide/dutasteride monotherapy, and my T went up from a norm of 950 all the way to 2000. The extra T is rather worthless though. Even at 2000 it isn't BAT.

Think of an analogy:

You have 100 one-gallon buckets that you are going to put out in a rainstorm to collect water.

1. It starts to rain and you put your buckets out. After a nice long rain you have 100 gallons of water.

2. It starts to rain and you put your buckets out. Someone sneaks up (Mateo for example) and fills 80% of the buckets with sand. Now the ground gets more rain but after the long rain you only have 20 gallons of water. Thanks a lot Mateo/bicalutamide.

Now for the Lupron/bicalutamide example.

1. It starts to rain and you put your buckets out. Lupron is on the scene and keeps 99% of the clouds away. So, after the scattered rain shower you have a total of 10 ounces of water.

2. It starts to rain and you put your buckets out. Lupron is still there. Mateo sneaks up again with his sand. Now you have just 2 ounces of water.

There is a little more to it but knowing all of the little details isn't important.

What would sort of be BAT-like in a way would be if you have very low SHBG and high natural T (my profile - natural T is 900-1100 and SHBG is around 18). If you used Lupron you would get a nice free T and bioavailable T flare - but the control of the timing and amplitude would be difficult and would change as time marches on. We have good ways to get T high with control, so the flare would be a roundabout way without much practical value.

Benkaymel profile image
Benkaymel in reply to smurtaw

Thanks Russ. I knew that ADT works by suppressing T production and there is T flare initially. Also, that ARs blocked reception of T so bicalutamide was used to deal with the flare - and of course, block the cancer from getting the T. What I didn't know until now was that the lutamides also substantially increased T serum levels. It seems counterintuitive.

Learn something new everyday!

Using your analogy about buckets, it's like when Mateo sneaks up and puts sand in them, it also causes the rain intensity to increase 10 fold! (However the buckets still only hold 20 gallons and Lupron still keeps 99% of the clouds away so it compensates for the increased rain.)

noahware profile image
noahware

If I was trying for a "high T" with thoughts of BAT, I would shoot for over 2000 (= "supra-physiological").

TreeDLeader profile image
TreeDLeader

I'm sorry, but posts with so much alphabet soup are so frustrating. I have no idea what you said.

MateoBeach profile image
MateoBeach

I’ll try to help: AA is abiraterone acetate, total inhibitor of testosterone synthesis. ARSI is androgen receptor signaling inhibitor also confusingly called AART inhibitors, advanced androgen receptor targeting inhibitors, and others! Refers to enzalutamide, apalutamide and darolutamide but not bicalutamide. AA is often grouped with these even though it is different in how it works. RCT is randomized clinical trial, the highest level of clinical evidence.

Within BAT, bipolar androgen therapy, SPT is Supra-physiologic testosterone or the High T phase. It alternates with very low testosterone cycles, castrate T or close to it. Smurtaw is experimenting with adding AA or ARSI to ADT to intensify his castrate T cycles.

smurtaw profile image
smurtaw in reply to MateoBeach

Yeah, what's up with the ARSI, AART, ARB... Now I find out that bicalutamide isn't referred to as an ARSI but it is still part of AART and an ARB.

Miomarito profile image
Miomarito in reply to MateoBeach

thanks so much Mateo, the abbreviations are too many to look up sometimes. This helps!

MateoBeach profile image
MateoBeach

See my reply to Yingsang above. Smurtaw is very smart but his regimen is indeed complicated!

smurtaw profile image
smurtaw

CYP17 is an enzyme. It is in the testosterone biosynthesis pathway.

smurtaw profile image
smurtaw

CYP17

Hormone chart

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