Zytiga & BAT

[paulmorin]

I am currently on Zytiga after Bicalutamide failed after 5 years, Would like to try BAT but not sure whether I should continue on Zytiga during BAT or discontinue until PSA goes up. Currently Testosterone is zero and PSA 4.5 and dropping. Prostate removed 20 years ago.

[Tall_Allen]

BAT had no benefit after Zytiga.. It only extended Xtandi.

[paulmorin in reply to Tall_Allen]

Is this based in data from a study or your own experience?

[Tall_Allen in reply to paulmorin]

In the RESTORE randomized clinical trial (RCT), the researchers investigated whether BAT can restore sensitivity to Zytiga and Xtandi to mCRPC men who have already progressed while using those. They give monthly testosterone injections until there was radiographic progression. The RESTORE trial found that BAT was able to restore responsiveness to Xtandi but much less to Zytiga.

• Following testosterone therapy, PSA declined by 50% in 30% of the group who'd previously taken Xtandi, and in 17% of the group who'd previously taken Zytiga. On these small groups, the difference wasn't statistically significant.

• After BAT, PSA declined by ≥50% in 68% on rechallenge with Xtandi and lasted 13 months

•After BAT, PSA declined by ≥50% in 16% on rechallenge with Zytiga and lasted 8 months

• There was no benefit to rechallenge with either in men with the AR-V7 mutation

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

BAT should only be tried within a clinical trial as it can be dangerous. Recent trials show that benefit is restricted to men with high AR activity, which occurs in about ⅓ of mCRPC patients. Xtandi (but not Zytiga or other advanced antiandrogens) prevents acquired resistance to T because it upregulates the AR while it inhibits it.

[Hidden in reply to paulmorin]

16% of men who saw a <=50% PSA decline on Zytiga after failing everything else would hardly be considered to have no benefit. ("BAT had no benefit after Zytiga") My husband was not one of the ones whose psa went down 50% or more on Zytiga but it did go down enough and is now where it was 4 or 5 months ago when he started. His doc considers that a big success. It would have been a lot higher now without the Zytiga.

Also worth mentioning if readers here are interested in BAT, there are better forums (even here on HU) and Facebook groups to get your information from men who have actually used BAT. The treatment is gaining momentum and more docs are getting onboard. MOs hopefully will see new information coming out of the recent ASCO conference.

There used to be quite a few smart contributors with good results on this forum but they chose to leave after seeing the same anti-BAT rhetoric in the comments. So actual user information is limited or has been deleted here. Please seek the other resources out if you are interested in BAT. You'll learn a lot.

[Hidden]

My husband had a very successful run with BAT after Zytiga and Xtandi both failed. He then successfully used Xtandi and Zytiga for the second time after BAT resensitized both drugs. He is currently on Zytiga (the first time he took Zytiga was 2017) with a rising psa waiting for Pluvicto.He did not take zytiga or Xtandi when he was getting the high T injections. He also had a "wash out" period where he waited to take Xtandi/Zytiga for a couple of weeks after BAT failed.

[GP24 in reply to Hidden]

Thank you for your post! It is interesting that BAT was able to resensitize for both Zytiga and Xtandi. You write: ".... after BAT failed." How did you determine that BAT failed?

[Hidden in reply to GP24]

He did BAT twice-- the first time he had approx eight 28-day cycles where PSA went down, then leveled off, then started to rise then finally spiked (doubling in a month). At that point doc was no longer willing to do BAT (it "failed") so started Xtandi. When Xtandi failed (very slow rise in psa over many months then rose quickly), he went back on BAT for 2 or 3 cycles. The last cycle caused his PSA to double in a couple of weeks so he then started Zytiga. PSA went down a few points, leveled off and has been slowly climbing the last few months (doubling in 4-6 months). PSA is now around 16 so the plan is to change course when PSA gets to 20 which is soon.

He will most likely get one reduced dose of chemo to qualify for Pluvicto but hopes not to have any chemo. His PSMA PET showed high avidity (SUVmax readings in the 30-66 range) so Pluvicto has a good chance of being effective for him.

The recent ASCO conference in Chicago a couple of weeks ago (40,000 oncologists) hopefully presented data showing Pluvicto to be effective without chemo opening the window for FDA approval without having to have prior chemo. That is coming but may not be soon enough for husband not to have a partial dose.

[Ramp7]

After I saw this video last year I met with Dr. Denmeade in person.

urotoday.com/video-lectures...

We had a rather engaging dialogue that lasted close to two hours. At that time I just completed a trial study at Dana Farber with LuPSMA177. PSA was rising. Prior to the study I had been on Zytiga and Lupron for 18 months, PSA was rising. During the meeting with Denmeade, Lupron was the only med I was taking. He said I was a perfect candidate for BAT. The next day I stated my own protocol, self administered using Propionate. Turns out I am indeed a responder. I have since completed 4 cycles. If and when BAT appears to have stalled, the plan is to resensitize the cancer with 2 to 3 weeks of Xtandi or Darolutimide. This protocol has not been endorsed my any of the MO's on my team or my Urologist but they are all kept up to date with my progress and have agreed to assist.

[dhccpa in reply to Ramp7]

You give yourself shots of T? Who prescribes? Thanks

[Ramp7]

I buy the needles and syringes from Amazon. The propionate I buy from an over seas supplier. steroids.click/product/prop...

I have a schedule set up with Russ's assistance. I told my local MO what I was going to do, so they were aware. As well as the MO at Dana Farber and Samuel Denmeade. Is wasn't endorsed but they were up to date on my doings. I also get regular blood tests. My local MO set up 22 blood tests at Quest for me. This is a rough outline. We can get into more specifics if you wish. Yes, I inject the T myself. The needle is so small, hardly feel. Instructions on Youtube.

Mark

[PCaWarrior]

BAT might resensitize Xtandi, Nubeqa, and Erleada. Much lower chance of Zytiga resensitization. Researchers speculate that this might be due to "residual" testosterone in the tumor microenvironment. That would explain it perfectly. But if this is true it opens the question of whether Zytiga would be resensitized after some delay. They started rechallenge immediately after BAT but maybe we need to wait a month or so.

If I understand correctly your question was about whether or not you should continue Zytiga during BAT. I do not know why Zytiga would interfere with BAT. But it is a risk since that doesn't match any clinicals. Perhaps ask Denmeade. He has stated that Zytiga should not be used with BAT. He also stated that Xtandi shouldn't be used. But when I asked him about it he said that a BAT program I am using interleaved with Xtandi is a valid approach.

My unscientific guess is that maybe the Zytiga would be an unnecessary drug since T biosynthesis will probably be swamped out by exogenous T and residual T. And it is possible that continuing this "unnecessary" drug during BAT will reduce its effectiveness down the road.