2nd pBAT cycle results: AR upregulation? Double strand breaks? Darolutamide?

[Ichthus316]

Started 2nd pBAT cycle on 4-22-24 with a PSA of 0.62 measured 2 days earlier. All 6 injections were 50 mg eod of T propionate with .625 mg letrozole every 5th day as an aromatase inhibitor.

The hiT cycle was cut short by 2 injections because of a plan to SBRT treat a pelvic lymph node chain that lit up on January’s PSMA scan. But my RO cancelled it after reviewing my 5-6-24 MRI and failing to see anything warranting treatment. He said the chain had "melted away."

Here are my blood test results during the cycle:

5-2-24, drawn 7 hrs after the last of 6 T injections

T = 2557

E2 = 6, will continue to reduce frequency of letrozole dose until E2 is > 10

PSA = 2.14, exactly the same as peak PSA at end of 1st hiT cycle (after 8 injections)

5-25-24, results at end of 2nd loT cycle, 23 days after last T injection:

PSA = 0.74, not close enough to original 0.5 baseline, so extended loT for 9 days

E2 = 35, upper end of ref range is 29 pg/mL; will reduce # of days on low dose E2 patch

6-3-24, results at end of 2nd full BAT cycle, 32 days after last T injection:

PSA = 0.58 (Started hiT phase of 3rd BAT cycle 6-4-24)

Questions:

1. A respected fellow BAT-man wrote that "a 4 week castrate period following a 1 week washout of the T-prop...is how long it takes for the androgen receptors (AR) to up-level in number and activity in preparation for the next high-t BAT cycle." Is that independent of hiT cycle length? True for everyone? Are there any studies?

2. Is it common for a PCa affected lymph node chain to “melt away” strictly due to ADT? If not, did the supra-physiological T part of the cycle destroy PCa (including stem cells) via double-strand DNA breaks, as the theory goes?

3. Next week, my MO plans to send Medicare a request to approve darolutamide in order to initiate a double blockade of T. How should that be worked into my next low T cycle?

[Ramp7]

You may wish to review Russ's book on Amazon. He provides links to ll the studies. amazon.com/Adaptive-Bipolar...

[Ramp7]

I think length of cycles is an excellent topic. Some are doing a much longer high T cycle. Maybe PSA length of response may also be considered.

[Hidden]

I have been on BAT + ARSi for 15 months: My findings being G9, no chemo:

1. In order to downregulate AR I know that 3 cycles works excellent, 1 is not enough. Next time I will perform 2 like in the STEP-UP trial.

2. In the AR upregulate phase with Daro PSA rises after 6 weeks, meaning resistance again.

3. During BAT I add 50% Olaparib, keeps PSA constant.

So, 2 Cycles with BAT + PARPi during 60 days, then ARSi with Daro for 6 weeks. I add Indomethacin to avoid AR-V7 by neutralizing AKR1C3.

[Ichthus316 in reply to Hidden]

Thanks for the info. Just to be clear on what you are doing, "2 cycles" means 2 injections of supra-physiological T cypionate 28-30 days apart without any ADT in the background, then switching to Daro for 6 weeks?

My initial 30 day cycles of 15 hiT & 15 loT were designed by Russ, presumably to see if I was a responder, and I am already at 30 days of loT. But it would seem that I may need to work toward extending both loT and hiT phases of the BAT cycle to at least 30-35 days each in order to re-sensitize the ARs to the next phase.

Since I am clearly hormone sensitive and still early in the BAT game, what do you think about this strategy: Extend each hiT cycle by 2 days (by a single Tp shot) and check PSA on the last day of hiT. In 6 months or less I should arrive at a 60 day cycle. If/when PSA begins to progress too rapidly, add a PARP inhibitor.

I know that PSA is overexpressed by T and is more important to monitor during loT, but I still worry about high PSA during any part of the BAT cycle.

[Hidden in reply to Ichthus316]

Answer is yes.

Got a PSA result yesterday, PSA 0.9 from 4.1 in 14 days using Daro. Expect 0.2 in the next month.

I am a no responder to BAT in the sense that PSA rises, BUT it obviously resensitize the cells extremely well, AR back to normal.

I am using Olaparib in 50 dose + Indomethacin.

[NPfisherman]

Great post.... Thanks for your case presentation....

I did my 2nd SBRT while T was higher, before starting abiraterone ... using eligard 2 days before my first session which causes T to rise initially.. and fall by the end of SBRT...

As for question 2--maybe... There are patients that start out with multiple mets, and they resolve with treatment over time....or they have a few left...(I call that resistance) and likely should be eliminated with SBRT or MDT... IMHO...

DD

[PCaWarrior]

If you have the onedrive link to my book, the present program I'm using is in it.

Essentially it is r-p-BAT. Olaparib strategically used for 4 days. Daro, Zytiga, E2, and Orgovyx used. I use prop and Androgel with one super fast pulse using oral T.

If you only have prop and daro it should work. An ADT underlay is important but daro might remove that requirement. Daro and Zytiga should eliminate it entirely. My additions haven't been trialed in the way I use them. So no real proof. I do lots of connect the dots.

[Ichthus316 in reply to PCaWarrior]

For when I'm ready for rBAT, where can I find Androgel? And how do you work it into a loT cycle when daro is used continuously? Or should it be in a cycle without daro? You can messenger or email me if you prefer.

[PCaWarrior in reply to Ichthus316]

Animal and cell studies often do not translate to humans. But for some reason hormone related ones frequently transfer well.

Going by animal and cell studies, it is very very very clear that hours to days is a slam dunk. It is also very clear that adding olaparib for a few days wipes out cancer. The rest is subpar. BUT we have lots of data for the month cycles.

I hope that a rapid BAT trial using Androgel and olaparib is performed someday. Both are legal. Both can be used. Both are extremely trial worthy. Results would be fast. The only problem I can see is that Androgel isn't FDA approved for the amounts we'd like. We can alleviate that problem a little by choosing little guys for the trial Seriously, that helps. And if we can use cyp and have an underlay of it, then we could use Androgel to pulse and use daro to cut it off. Might need to extend the week cycles a bit... 10 days?

[PCaWarrior]

Androgel can be obtained with a prescription. Or you can get cernos gel black market.

I stop daro 7 days prior to using 600 mg of cernos. T goes just over 2000.

7 days later I repeat 600 mg cernos.

7 days later I repeat 600 mg cernos and start daro the following day.

My lowT phase is longer when I do rBAT. But if you only do rBAT once the cycle can stay about the same. And if you don't use daro you can do more rBATs.

[Ichthus316 in reply to PCaWarrior]

Can a single injection of propionate be used for rBAT, followed by full dosing of daro a day or two later?

[PCaWarrior in reply to Ichthus316]

Yes. I do that sometimes. You can almost achieve the same short pulses. But you either need to adjust the T after daro or let the daro clear for at least 5 days.