Xtandi monotherapy is very effective

[GP24]

(Zoom your browser to read the image)

At the AUA2023 the results of the EMBARK trial were presented. This phase 3 randomized trial had three arms and compared in patients with high-risk biochemically recurrent prostate cancer:

- enzalutamide plus leuprolide

- enzalutamide monotherapy

- placebo plus leuprolide

The primary endpoint was metastasis-free survival (MFS). The enzalutamide monotherapy was almost as effective as enzalutamide plus leuprolide with fewer hot flushes, hypertension, falls and fractures. The reduced fractures show that the monotherapy avoids bone loss. Therefore, Xgeva is probably not required. The monotherapy can be used to avoid these side effects.

I added the curve for enzalutamide monotherapy into this image for comparison and included the tables of adverse events. There is increased gynecomastia and nipple pain with the monotherapy. I think this can be avoided by combining it with 20 mg Tamoxifen.

[SViking]

That’s very interesting. Would the same old true for Zytiga? And what about if castrate resistant? Could Orgovyx be stopped and just a Zytiga used?

[GP24 in reply to SViking]

According to the SPARE trial, yes: pubmed.ncbi.nlm.nih.gov/354... However, if you make Zytiga monotherapy you just help your health insurance. Zytiga lowers testosterone even better than Lupron and therefore there will be no change in side effects.

[StayingOptimistic in reply to GP24]

I am confused, I thought Zytiga blocks the AR and does not lower T. it’s an anti-androgen.

[GP24 in reply to StayingOptimistic]

Zytiga stops testosterone production better than Lupron. So the testosterone level gets lower when you take Zytiga. It is not an anti-androgen. Enzalutamide, Apalutamide and Darolutamide are anti-androgens. But not Zytiga.

[StayingOptimistic in reply to GP24]

I am not sure if this is correct.

Found this online goggle

[GP24 in reply to StayingOptimistic]

Abiraterone is mentioned as an antiandrogen, but it does not block the androgen receptors. It inhibits androgen (testosterone) production as an androgen biosynthesis inhibitor. See e.g. this article:

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

"In contrast to canonical antiandrogens which target androgen receptor, abiraterone acetate is an androgen biosynthesis inhibitor, [...] As such, it targets [...] CYP17. CYP17 processes testosterone and is produced in the testes and adrenal glands. Therefore, inhibition of CYP17 prevents androgen production [...]

[StayingOptimistic in reply to GP24]

thank you.

[SViking in reply to GP24]

So, if Zytiga does a better job at shutting down, testosterone, why don’t oncologists give us a Zytiga from the beginning and skip the Lupron or Orgovyx?

[GP24 in reply to SViking]

The FDA approval does not include non-metastastic hormone-sensitive patients yet.

[SViking in reply to GP24]

so if somebody was already on Orgovyx and Zytiga, as approved by insurance companies, they could just stop taking the Orgovyx and continue with Zytiga? Would that be no difference in controlling this disease?

[GP24 in reply to SViking]

From what I know, yes. However, you would do that to reduce side effects. But these will be the same, the testosterone is low.

If you would be an Orgovyx and Xtandi and then drop Orgovyx, after testosterone has recovered, which can take a few months, you should feel better.

[dhccpa in reply to GP24]

We just need a cheap generic version of that.

[KocoPr]

Thanks. So im thinking with all that T floating around in your system not being used the excess is being shunted down the aromatase pathway to estrogen thus gynecomastia and nipple pain. Am I thinking wrong on that? I have COMT and GSTP mutations that showed via testing just before i was diagnosed back in 2013 that my good to bad estrogens were way out of balance and referenced it being very carcinogenistic. Which I suspect many PCa patients had out of balance estrogens which caused their cancer.

I will need to study Tamoxifen

[GP24 in reply to KocoPr]

I cannot comment on COMT and GSTP mutations. In men, testosterone and estrogen are in balance so that the breast does not grow. Xtandi monotherapy will increase the testosterone level and get testosterone and estrogen out of this balance. The same effect occurs with Bicalutamide.

pubmed.ncbi.nlm.nih.gov/352...

pubmed.ncbi.nlm.nih.gov/162...

[tarhoosier]

I have been on Xtandi monotherapy for 6 1/2 years and this may support the decision my oncologist made to pursue this treatment. I have a metastasis recently identified in lumbar area using PSMA scan so this treatment may change. Consultations coming soon.

[treedown]

Having taken Lupron with Zytiga previously and Lupron and Xtandi now I have to say that the latter combination seems harder on my system. Time will tell if it is the right choice and I am hoping to adapt to it over time. If not I may decide to lower the dose of Xtandi if/when I hit undetectable as I did with Zytiga during my first 2 year stint.

[GP24 in reply to treedown]

When Zytiga stops working Xtandi will work for a short while only. There is a cross-resistance.

[treedown in reply to GP24]

Thats how I understand it so zytiga and all the lides are the same stop gap.

[GP24 in reply to treedown]

Zytiga lowers testosteron very effectively while Xtandi blocks the androgen receptors plus additional effects. So with Xtandi (without Lupron) you will have fewer side effects like hot flushes, bone loss etc.

In you situation Xtandi monotherapy will not be the right thing. In the study were patients who had rising PSA just after surgery or radiation.

[treedown in reply to GP24]

Thanks. I never considered it as a monotherapy but many here have had success with a reduced dosage to ease side effects so I will keep that as a consideration. My bloodwork is good so not ready to give up on full dosage yet.

[CAMPSOUPS in reply to treedown]

I hope your doing better on Xtandi than I did these last 3 months. I stopped this past week because I was progressing on it anyway.

I'm just writing in the misery loves company belief lol.

Zytiga was a walk in the park for me. Xtandi not at all (however still to see how much was the Xtandi and how much the progression of PC ).

I can see how you might have not got on your bike much. I was and am still to some extent (half life of Xtandi is 3 to 10 days) having a hard time finding pleasure in anything. Zoning out, staring at the wall. Its gotten better though and especially the vertigo has improved since I stopped Xtandi about 6 days ago.

This not finding pleasure, zombie effect I am finally going to do something about. 3 years I think was long enough not to bring it up and ask about Effexor (Venlafaxine is used to treat depression. It may improve your mood and energy level, and may help restore your interest in daily living ).. My prescription should be ready to pick up tomorrow. I'm hoping for a turn around in mental outlook and of course it is known to lessen hot flashes as well. I alway remember a thread from a couple years ago. A long thread discussing pros and cons of such meds and finally/bluntly one responder said "Geeez if your diagnosed with stage four cancer your first prescription should be anti-anxiety, ant-depression" ! I alway found that humorous.

Hoping you can adjust to the Xtandi or that your PC/PSA will come down/stay down long enough to experiment with lower dose. Maybe a question for your MO would be is it safe to eliminate Xtandi for 5 days to clear it out then start on smaller dose and ramp up etc. if necessary. But I know how scary that is. Want to continue to hit it hard.

[treedown in reply to CAMPSOUPS]

Not better yet but not worse.. If I had to grade my side effects they would be closer to 1 than so I will give it more time. it could be that my family is dealing with a cold or could be covid but could be nothing, the wife has something for sure. Too little to take a test but she might today and if me and the kid had it we might have breezed through it. I can feel my brain muddled more at certain times than others. I maybstart taking the Xtandi at night, feels like I mentioned that already. This weekend was great and good weather ahead for more time on my bike. I could see a benefit of a mood stimulator if I can't ride so maybe next winter. Let me know if you decide to go that way and how it works out.

Do you have a strategy going forward yet. Your back on chemo right? How long will that take?

[CAMPSOUPS in reply to treedown]

Well that's kinda good that maybe cold virus going thru your family on top of winter doldrums probably. Weather in the twin cities finally turned the corner about a week ago so I will be shore fishing before too long.

My recent chemo was a bust. 3 infusions and no benefit instead beat me up pretty bad. Much different experience than 3 years ago.

That's why Xtandi was started 3 months ago but that has not worked either so I've been off it for about 7 days.

Next choices are Pluvitco but with shortage off the table for now although I have a PSMA PET scheduled.

Jevtana/Cabiztaxel vs. the Docetaxel I had that failed me but more chemo now when I'm still beat up from it not the best solution.

So, and I am optimistic about this I am starting the initial bloodwork, consent forms to get approved for a trial which might keep my progression at bay for a while or at least long enough until Pluvitco is available.

This trial drug is phase 2 no placebo and I summarize it as a generation 3 ADT drug. Its the Orion CYPIDES Trial. Keeping my fingers crossed of course.

Well get out there when you can and enjoy the weather/biking. Hope your family/wife don't have any cold/covid issues to deal with.

Cheers.

[treedown in reply to CAMPSOUPS]

I'll check out that trial and hope for your entry. Let us know how it goes. Its been a long day of work so thinking I'll put the bluetooth headphones on and cut the yard. Gonna take a long ride tomorrow with a friend and work can suck it

Peace

[CAMPSOUPS in reply to treedown]

Cool that sounds like a plan. Enjoy!

[Brysonal in reply to GP24]

Very interesting thread. So could Zytiga be used for BAT instead of Orgovyx or does it take too long to drop testosterone levels?

[GP24 in reply to Brysonal]

I do not fully understand your question. BAT means you get a shot of testosterone while on ADT. The shot will increase testosterone much above the normal level and the ADT, which is not interrupted, will take care to lower the level again to castration. You can use lupron or Orgovyx for ADT, maybe Zytiga as well. Do not add Xtandi, Darolutamide or Erleada.

[Brysonal in reply to GP24]

It may be a daft question so appreciate the prompt response. We can’t get Orgovyx in UK which from my reading is used by many on modified BAT to remove the testosterone in the ADT cycle quickly. Without Orgovyx I didn’t think modified BAT was worth discussing but this thread made me wonder if Abiraterone can be used to remove testosterone but I may be misunderstanding - it was just a thought

[GP24 in reply to Brysonal]

You can replace Orgovyx with Firmagon which has about the same effect.

[dhccpa]

Anything out there about monotherapy with generic abiraterone acetate?

It seems like that should have been compared head to head.

[docbulldog]

I continue to lean toward going back to Xtandi following my current chemo regiment. Three years ago I had success for over two years, and I’d like to try it again.

I’ve read several of you on this site had returned to Xtandi and had success. My Defense, then was Ellegaard, Xgeva, and Xtandi.

Thank you for any information and best of luck to those of you that are on Xtandi.