Advanced Prostate Cancer

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Zytiga with BAT

2 months ago•46 Replies

Does anyone have any opinions on combining AA with BAT?

I know that the conventional wisdom is that this should not be entertained. However, I can't think of a good reason not to reduce all sources of T during the ADT phase of BAT. During the high phase, the production should slowly recover and since we are relying primarily on membrane AR activation provided from exogenous T, does a reduction of intracellular T pose a problem?

I am thinking of using AA during the low phase of BAT for 3 cycles and then letting it wash out and the CYP17 enzyme recover for two cycles. 3/2/3/2... I would use bicalutamide for the first week of every low T phase.

My interest in using AA is guided by a recent nightmarish experience with Xtandi.

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smurtaw

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Seasid2 months ago

I am interested in something. How do you feel during these low and high phase of T? Do you feel different when it is in transition? Changing?

smurtaw in reply to Seasid2 months ago

I feel like a million bucks on the high T cycles. Libido, muscle, strength, happiness, vitality.

I don't feel bad on the transitions. And normally on the low T phases I use SARMs and still feel ok with some libido, some muscle, some strength, some happiness, and some vitality. But Xtandi crushed me.

Seasid in reply to smurtaw2 months ago

Thanks

Spyder542 months ago

Russ, from everything I have read, you want your low phase to bring you back to complete undetectable PSA, I would assume you want your T also close to zero. Castrate levels (less than 50), as a minimum. It only makes sense to add Zytiga/Abiraterone Acetate to make this happen. Ideally in 30 days, so yoou can get back to a high level of T for 2,3, or hopefully 4 months. Keeping your PSA in check for that high cycle.

Not sure what your issue was with Xtandi? For me, early on, it allowed my T to rise gradually, then PSA followed. When I switched to Lupron/Zytiga/pred, my T dropped to zero and PSA reversed and starting to descend again.

It is early days for BAT. EVERYONE SEEMS TO RESPOND DIFFERENTLY. One thing seems certain, that the std protocol of 30 days high T followed by 30 days low T is too rigid and mechanical. We all wait to learn if this may prolong the time to Hormone/Castrate Resistence. Mike

cesces2 months ago

Have you considered using some of the older androgen deprivation drugs?

The part of BAT isn't the testosterone low, but the testosterone high.

There are even docs that will do just the high without the low.

So maybe you are asking the wrong question?

smurtaw in reply to cesces2 months ago

I use Lupron continuously and use a low dose estrogen patch during the low phase. I have the high T phase fairly well defined.

I'm wondering about adding AA to the low phase. It makes sense but I haven't seen any study data about combining AA with the low T phase of BAT (only sequential data which does not apply).

Sometimes I use bicalutamide during the ADT phase. Gets me a sharper effective androgen drop-off. Xtandi wasted me or I would use it instead of Zytiga. Hence the question about Zytiga.

cesanon in reply to smurtaw2 months ago

Why don't you take a consultation with Dr. Denemead.

There is no substitute for experienced professional intuition on a nuanced subject like this.

smurtaw in reply to cesanon2 months ago

I've contacted my MO. I think she might need to request a referral so that my insurance pays for it. And I'm not sure who I want to see. A younger doctor who might be more sympathetic to listening to me about BAT while HSPC or an older one?

I found one young female doc who works with Denmeade and used to work with Antonarakis. She is involved in the BAT clinical that uses oral testosterone undecanoate. We started conversing because about my use or oral T. I'd never heard of anyone using it for BAT but of all places, found out on twitter.

cesces in reply to smurtaw2 months ago

Denemead is the one with the most experience and the highly developed intuition, presumably.

He started this BAT thing. And everyone who is anyone in the field is talking to him. Not including peer review activities.

A second opinion from him isn't going to cost that much out of pocket.

Why not select the best tool.

smurtaw in reply to cesces2 months ago

Denmead probably knows as much as anyone about BAT.

What prevents me from consulting with him is that he is very adamant that BAT can only be used for CRPC men. One of my friends consulted with him and was shut down as soon as it was revealed that he wanted to do BAT while he was still HSPC. I don't want to waste my time and money just to be told "no, do not do it".

Morgentaler, Schweitzer, and Lieberman did BAT on HSPC men. I tried to consult with Lieberman 3 years ago but he was retiring. Schweitzer won't talk to me unless I am a patient at his hospital. I'm not sure about Morgantaler.

cesces in reply to smurtaw2 months ago

Try Sartor at Tulane. He isn't generally reluctant to paint outside the lines.

And his consults don't cost a lot.

smurtaw in reply to cesces2 months ago

Thanks!

Gearhead2 months ago

Remember that you need prednisone (or alternative) with AA, and that should be tapered when stopping AA. Moreover, even though Zytiga guidelines on prednisone are clear (5 mg/d if CS, 10 if CR), many of us have found that prednisone dose needs to be adjusted, or an alternative works better, for our specific situation.

smurtaw in reply to Gearhead2 months ago

Valuable point. I'm very aware of this and aware of the CYP17 recovery time and Zytiga washout time. But not everyone is. I even heard of an MO who told one of his patients to stop prednisone when he stopped Zytiga!

Tall_Allen2 months ago

It's not "conventional wisdom." There is clinical evidence. BAT was tested after Zytiga and it didn't work very well. Much better after Xtandi.

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

Schwah in reply to Tall_Allen2 months ago

TA, how on earth can you possess so Much knowledge so much PC TA? It’s amazing and so helpful. How much time do you spend in a typical week studying the latest info?

Schwah

Tall_Allen in reply to Schwah2 months ago

Thanks. I have good retention. You don't want to play Trivial Pursuit against me. lol

smurtaw in reply to Tall_Allen2 months ago

This has some discussion of RESTORE and TRANSFORMER and the statement that Zytiga should not be used with BAT.

Bipolar androgen therapy (BAT): A patient's guide - Denmeade - 2022 - The Prostate - Wiley Online Library

onlinelibrary.wiley.com/doi...

“BAT should not be combined with Zytiga, Xtandi, Erleada, or Nubeqa (or with taxane chemotherapy).”

As far as I know though, what I was pondering has not been studied - Zytiga with BAT (I read the statement but I’m not certain how they determined that Zytiga, Xtandi, Erleada, and Nubeqa should not be part of a BAT program). Zytiga or Xtandi to failure before BAT and then a rechallenge has been studied. But I wasn’t going to do sequential therapies. I was considering combining them.

If you know of any studies that show the use of Zytiga in conjunction with BAT please let me know. Or if you can think of reasons why Zytiga would harm BAT could you outline them?

By the way, I was never good at trivial pursuit.

Seasid2 months ago

Did you have a bone density scan?

Seasid2 months ago

After 4 years on ADT (Degarelix) I am osteoporotic now.

Miomarito2 months ago

I was thinking g about you, Smarty and relieved you are doing better…. I hope you find your answers to this complex disease, a parasite that feeds off of its host in a most voracious way. Thank you for explaining the terms in your last post.

smurtaw in reply to Miomarito2 months ago

Thanks M. The ups and downs are like being on a rollercoaster. But one that breaks down a lot and might careen off the tracks at any moment.

MateoBeach2 months ago

You are more into micro managing cycles than I am. I do agree that having extremely low T during castrate cycle makes sense, and AA would do that. However, since I am only doing one month periods castrate, I am reluctant to need to add and then withdraw the low dose prednisone with the monitoring and titration that may require. And also reluctant to use Xtandi for the SEs. That is why I am considering Nubeqa as preferred addition to Orgovyx.

(BTW, correcting an earlier comment from someone else, Orgovyx does indeed cross the blood-brain barrier. It’s action is on the hypothalamus blocking release/effect of LHRH on pituitary LH.)

smurtaw in reply to MateoBeach2 months ago

Perhaps slightly counterproductive but possibly half or full dose AA continuously. I wouldn’t think it would matter a lot since Lupron (or whatever ADT drug we are using) is going to take care of most testes T. The adrenal and tumor T only accounts for maybe 6% of the exogenous amount. Should be less than 60 ng/dl. We can easily overcome that with exogenous T.

The reason I micromanage so much is that I simply LOVE BAT and do not want it to end. I love the libido, the muscle and bone gain, and no pain in my joints or back. And I have so much energy that I have a hard time staying asleep at night (that’s arguably the only good side effect of Xtandi – I sleep a solid 8-9 hours every night).

KocoPr in reply to MateoBeach2 months ago

Thanks for correcting my erroneous statement on Orgovyx crossing BBB.

Always good to make accurate statements and be corrected if not accurate. That’s what I love about this forum, it is chock full of knowledge.

smurtaw in reply to KocoPr2 months ago

I think you were thinking about Darolutamide. It doesn't cross the blood/brain barrier.

Most of the side effects from Orgovyx/Lupron/FIrmagon/etc. are due to low T and not the BB barrier. There seems to be real side effect reduction when using Darolutamide vs other ARSIs. And you know what I think of Orgovyx. I wish my insurance agreed with us.

Spyder542 months ago

Russ, another question: during the low T phase, you mentioned Xtandi did not work for you. Have you considered a 30 day, single injection of Firmagon? It worked well for me in my 1st month at Dx. Lupron, of course is known to give an initial spike in T, so it would not be a good choice. My understanding is you are trying to get down to castrate levels of T as soon as possiblle after your 3 month or 4 month phase of Supra Physiological High T, a single injection of 30 dayFirmagon may be perfect, then back up you go to happyland. If T not down <50, or better <20, then gut out a 2nd 30 day Firmagon injection? Mike

smurtaw in reply to Spyder542 months ago

Mike, I started with Firmagon. Then I switched to Lupron. It's a GnRH agonist so produces a T flare so I timed it with a high T phase (Lol - T flare became beneficial!).

There is study data showing that Xtandi resensitizes SPA. That's why I wanted to add it. The side effects are too extreme for me so I am dropping it.

When doing BAT, we can have our body's internal testosterone always low. And then we create a high testosterone phase using testosterone injections/gels/or orals.

Seasid in reply to smurtaw2 months ago

INTJ always over engineer things.

That is an INTJ weakness. I am just warning you. I was reading socionics.com INTJ uncovered profile.

I would follow MateoBeach.

I am just trying to save you from your personality type weakness.

Seasid in reply to Seasid2 months ago

You can't deny that INTjs are pretty adept at many things, but one thing INTjs are really good at is over-tightening the screws, whether it is said in a metaphorical or in a literal sense. Having natural inability to judge amounts and distributions of forces often leads them to overdo things. For instance, if you ask an INTj to design a good chair to withstand the weight of one adult, when it is finished it would probably withstand the weight of one adult elephant.

Seasid in reply to Seasid2 months ago

From socioncs.com:"INTjs take little or no notice of what other people think. What they think themselves is much more important to INTjs. That is why if everybody is certain that bridges have to be built across the river, an INTj may contemplate the possibility of building one along the river. There would probably be a logical reason for that since INTjs view everything through the square prism of logic. And as long as logical rules are obeyed everything is fine."

smurtaw in reply to Seasid2 months ago

Have you seen the weight of some people?

Seasid in reply to smurtaw2 months ago

Ok, I agree, the general population is stupid.

smurtaw in reply to Seasid2 months ago

My ex-brother-in-law is one of the smartest guys I've ever met. Also, one of the fattest and one of the nicest.

Fat does not equal stupid.

Seasid in reply to smurtaw2 months ago

My sister is also like a tank.

noahware2 months ago

I have wondered, why not use AA alone for the low-T phases?

smurtaw in reply to noahware2 months ago

I wondered the same thing. Constant AA would get most of the endogenous T out of the picture.

I talked to my MO and she said that most guys in her practice who have tried to use AA for ADT see their T go up so they add Lupron back.

Do you know of any studies that show how fast AA reduces T? I remember one study but I don't recall the details.

noahware in reply to smurtaw2 months ago

"The first in-human dose escalation study of abiraterone was published a decade later [O’Donnell et al. 2004]. In non-castrate patients diagnosed with prostate cancer, abiraterone was shown to rapidly decrease serum testosterone to castrate levels. However, the compensatory increase in LH led to an increase in serum testosterone to non-castrate levels in some men. For this reason, future development of the drug was done in conjunction with ADT. It was noted that, while cortisol levels were unchanged following abiraterone, adrenocortical suppression lead to impaired response to exogenously administered ACTH."

This is from that 2004 paper:

"Suppression of testosterone levels to <0.14 nmol l−1 was seen in four out of six castrate males treated with a single dose of 500 mg. At 800 mg given days 1–12 in noncastrate males, target suppression was achieved in three out of three patients, but a two- to three-fold increase of Luteinising Hormone (LH) levels in two out of three patients overcame suppression within 3 days. Repeated treatment of men with intact gonadal function with abiraterone acetate at a dose of 800 mg can successfully suppress testosterone levels to the castrate range. However, this level of suppression may not be sustained in all patients due to compensatory hypersecretion of LH."

lookingforamiracle2 months ago

I have wondered about but never seen any discussion or study using high dose E2 for ADT on the low cycle.

smurtaw in reply to lookingforamiracle2 months ago

Unfortunately, I don't think it would work. It takes about 3-5 weeks for T to drop when using high dose E2 (it took me 5 weeks and I was close to giving up given all the disinformation given to me by MOs).

If we could continue it constantly it should work with some benefits on the ADT phase. But it is probably not a good idea to have high estrogens during the SPA phase.

lookingforamiracle2 months ago

Ah, rapid swings look to be key with BAT. Thanks for your thoughtful reply. Unfortunately, the MD who was going to be willing to work with me on some form of BAT died at the end of August, so I am currently left as an observer of you brave guys. I have brought Denmeade to my MO's attention, and he's open but cautious. Four plus years of Lupron and Eligard and now AA since April are really sapping my vitality. I see him again tomorrow, so I will talk with him about BAT again then. Good luck.

smurtaw in reply to lookingforamiracle2 months ago

Thanks. I hope you find an MO who will help. Would clinical trial data help nudge him to try it? There are some new trials in the works that are better IMO than the ones that have been completed.

lookingforamiracle2 months ago

Clinical data would certainly carry the most weight. It would help me also move from leaning in that direction to actively pushing for BAT.

Seasid in reply to lookingforamiracle2 months ago

The Strengths and Weaknesses of Bipolar Androgen

Therapy

A. Edward Friedman

Abstract: It has been shown that when the amount of intracellular androgen receptor in prostate cancer is

greatly amplified, such as in the cell line LNCaP 104-R2, then testosterone will stop the growth of those

cancer cells. This is the principle behind bipolar androgen therapy, which alternates amplifying

intracellular androgen receptors by using very low levels of testosterone with supraphysiologic levels of

testosterone. This approach has achieved some limited success in human patients. However, as these

cycles continue, some mutations are expected to arise that give the cancer cells a selective growth

advantage and lessen the effectiveness of bipolar androgen therapy.

smurtaw in reply to lookingforamiracle2 months ago

This list is from my book. I don't know how to easily transfer it here in a correct format. But the URLs are clickable. RESTORE on down are complete. The top half is recruiting.

My general opinion of the therapy scheme’s effectiveness (1-10 – the higher the better). Trial URL Estimated enrollment Who Therapy Est primary completion Est study completion

3 Square Wave Testosterone Therapy in Castration Resistant Prostate Cancer

Non-randomized

clinicaltrials.gov/ct2/show...

15 CRPC transdermal gel testosterone alternating with Xtandi Aug-24 Aug-25

4 COMBAT-CRPC non-randomized clinicaltrials.gov/ct2/show... 44 mCRPC BAT (1): Nivolumab starting cycle 4 Sep-22

Nov-23

8 ExBAT non-randomized clinicaltrials.gov/ct2/show... 47 mCRPC Alternating 56-day cycles of darolutamide 1,200mg/day (two 300 tablets every 12 hours) p.o. for 28 days followed by testosterone cypionate 400 mg IM Apr-23 Apr-24

3 BAT-RAD non-randomized clinicaltrials.gov/ct2/show... 47 CRPC BAT (1) plus Radium-223 (RAD) Feb-26 Feb-27

4 Hi TeCH non-randomized clinicaltrials.gov/ct2/show... 30 CRPC, Genetic HRD 500mg IM enanthate every 4 weeks in combination with ongoing LHRH agent (unless post-orchidectomy) plus Carboplatin AUC 5 Dec-22 Dec-22

1 VA-BAT non-randomized clinicaltrials.gov/ct2/show... 51 CRPC, Genetic ATM, CDK12, or CHEK2 BAT (1) Aug-26 Aug-27

9 STEP-UP RCT clinicaltrials.gov/ct2/show...

150 CRPC BAT (1) interleaved with Enzalutamide in two schemes Jul-25 Jul-26

8 Oral-TU/Xtandi

RCT clinicaltrials.gov/ct2/show...

30 mCRPC Oral Testosterone Therapy-396 mg given twice per day on days 1-7 and 15-21 of a 28-day cycle until radiographic progression. After a 21-day washout period, Enzalutamide therapy given at 160 mg once daily will be taken for a maximum of 6 cycles while on study. Dec-25 Dec-27

NA RESTORE non-randomized clinicaltrials.gov/ct2/show...

Actual 112 CRPC Men who failed Xtandi or Zytiga received BAT therapy. After BAT therapy most of them were rechallenged with Zytiga or Xtandi. Complete Complete

NA non-randomized clinicaltrials.gov/ct2/show...

Actual 36 CRPC Testosterone enanthate 500 mg IM every 28 days. Olaparib 300 mg every day

Complete

NA TRANSFORMER RCT clinicaltrials.gov/ct2/show...

Actual 222 mCRPC BAT (1) vs enzalutamide Complete Complete

NA BATMAN non-randomized clinicaltrials.gov/ct2/show...

Actual 33 HSPC 6-month ADT lead-in. Alternating 3-month cycles of ADT and BAT (1) Complete Complete

NA PSMA-BAT non-randomized clinicaltrials.gov/ct2/show...

Actual 20 mCRPC BAT (1) Complete Complete

NA Men's Cycle non-randomized clinicaltrials.gov/ct2/show...

Actual 36 mCRPC BAT (1) Complete Complete

(1) 400 mg of testosterone cypionate (or enanthate) injected once a month. Standard ADT Lupron treatment.

lookingforamiracle2 months ago

Thank you both for all this info.

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