I know there is great interest in the BAT trials. This one combined a PARP inhibitor, olaparib, with BAT. Here are the results:
30 heavily-pretreated men who were mCRPC and who have progressed on either Zytiga or Xtandi, received BAT and the PARP inhibitor olaparib. 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, 8 >90%
• 5 patients had PSA doubling, 6>90%
• 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
This trial suggests that BAT + olaparib achieved good response regardless of DNA damage repair defect status. The cause of responder/non-responder differences remains elusive.
I'm a little confused... And correct me where appropriate. I thought BAT was an alternate between ADT, keeping T low, and then stopping that while receiving a mega-blast of Testosterone in the interim.
Per the study:
The authors performed a single center phase II trial testing olaparib (300 mg PO BID) plus BAT. BAT was administered with intramuscular T cypionate/enanthate 400 mg every 28 days while continuing androgen deprivation to suppress endogenous T.
While continuing the ADT the other drugs were given?
My question would definitely be the intervals and the amounts and durations of each phase...
I believe that BAT involves continuing ADT e.g. Lupron and then getting a monthly bolus of T. This will spike the T levels to hopefully overwhelm the PCa that have mutated to live with Low T. Then the T will descend rapidly down to, hopefully, castrate levels. This would then deprive the PCa that thrives on High T.
BAT involves keeping one on ADT. Then, every 28 days, he gets a shot of T cyp/enan with a half-life of about a week, so no T left by the end of the month, effectively alternating castration and high T.
Exactly! Only the four week cycles of two weeks on high T and two weeks castrate have been formally studied to any degree. That timing may well not be optimal for slowly dividing PC. (I am currently testing a four month cycle in myself: two months of T-cyp 400 mg every two weeks, then two months of no testosterone. ) off the reservation.
My doctors and I are planning to test various timing. My PSA started going up (0.15) and now I'm going to start a pseudo BAT plan.
400 mg T cypionate shot.
2-4 weeks later, 50-150 mg/day Casodex and a SARM (1 mg/day ligandrol).
5 weeks later stop the Casodex
1 week later rinse and repeat
I plan to test PSA twice a month so that I can intervene if needed.
One of my doctors agrees with my plan on paper. I have a meeting with the other one on Monday. Hopefully, I can get answers to two of my questions: Will Casodex block ligandrol action? So I might have to go to a lower dose of Casodex (25 mg?). Would it be prudent to add Xtandi?
Odd, even though my PSA has gone up I am excited about the possible new therapy. If it doesn't work, perhaps estrogen patch therapy again (effectively ADT). Or perhaps Casodex monotherapy. Or maybe standard BAT. Perhaps radiation. But this is all jumping the gun.
Yes. My doc is writing a script for the ligandrol. He ran into a snag today though. The compounding pharmacy that he uses no longer carries ligandrol. So, either another compounding pharmacy or a different SARM.
This is my modified BAT approach. I'll be monitoring PSA and changing the timeframes as dictated. This graph shows that they are fixed but in reality, they aren't set in stone. If it doesn't work I'll throw it out and try radiation, or chemo, or whatever my MO suggests (I'm meeting with her in 3 weeks). At first, I'm going to be doing sort of an ADT. I've been on super high T for 2 years now and my endogenous T should be zero (LH and FSH are undetectable). So I likely only need to worry about the half-life of cypionate and how long it will take to leave my system. Casodex should effectively take care of that (I've used it before).I might add Zytiga or Xtandi to the ADT phase. Depends on what my MO recommends.
Well, it's just PSA and just 12 weeks. And not so good for the 8 who had large increases in progression. No clue yet on how to predetermine responders from progressors. Maybe they all would be better off with a PSMA-targeted therapy or one of the myriad other clinical trials.
Signal vs noise? Could the BAT responders vs non-responders be interpreted as independent of their genetic susceptibility to the PARP signals of DDR deficiencies present or not?
Timely post for me. I have not responded to Zytiga after a 2+ year response to Xtandi. PET scan today and labs. Meet with my oncologist next Tuesday for plotting the next treatment. My genetics say Olaparib might work but not sure since I have both small cell and adenocarcinoma cell lines still active. Thanks for sharing this article. Wish we could move faster in this country on PSMA scans and PSMA treatments but I realize that the FDA has bigger issues to deal with right now.
Thanks for information on Olaparib. I have CHEK2 gene mutation and ONC said PARP inhibitor likely to be next treatment option. Just started Xtandi after completing Docetaxel last week. Have bone mast, PSA is 27 see what happens. Looking for trials.
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BAT: Bipolar Androgen Therapy: A Paradoxical Approach for the Treatment of CRPC.
Bipolar Androgen Therapy
Bipolar Androgen Therapy results?
Androgel for bipolar androgen therapy
Bipolar Androgen Therapy for mPCA
