Do Apalutamide and Darolutamide go alongside prednisone?

[tarzantass]

Appreciate you whether Apalutamide and Darolutamide must go alongside Prednisone when taken. A million thanks.

[Tall_Allen]

No. Prednisone is only taken with abiraterone because it must replace the cortisol that abiraterone blocks.

[tarzantass in reply to Tall_Allen]

Thanks Tall Allen

[tarzantass in reply to Tall_Allen]

Hi Tall Allen!

Your feedback is more reliable than ChatGPT, which says “Prednisone must be taken alongside Apalutamide or Darolutamide. I would rather go with you ‘cause you have so much experience in the treatments of prostate cancer. Thanks for that quick response.

[JRLDH in reply to tarzantass]

The problem with ChatGPT is that it's dazzling without justification. I feel it's like the most eloquent, confident random entity with zero experience but access to Google. I would never use it for medical advice. NEVER.

I think besides taking advice from well respected forum members, this question can be answered definitively with the prescribing info for these drugs.

Abiraterone mentions Prednisone:

janssenlabels.com/package-i...

Apalutamide and Darolutamide do not:

janssenlabels.com/package-i...

labeling.bayerhealthcare.co...

[tarzantass in reply to JRLDH]

Thanks JRLDH. It’s true to say never get any medical advice from ChatGPT.

[JohnInTheMiddle in reply to Tall_Allen]

So simply put! And as we know correct! 😃 In this context, one could add that Abiraterone also blocks estradiol, another steroid just like cortisol. You know, "just to complete the picture".

Of course, blocking estradiol has so many cascading side effects, although maybe not as immediately serious as blocking cortisol.

Therefore, it's not surprising of course that some people advocate for "low-dose estradiol add-back". Just like prednisone for cortisol. Seems so simple.

You may recall my own pursuit of this topic on this forum. But I have given up the question and haven't done anything about it. I don't wish to become an advocate, as an amateur. On questions of metastatic prostate cancer therapy, I'm only looking for research and support from experts.

I would be grateful though if you could share again "why not estradiol low-dose add-back?" Because the potential benefits seem important enough to pursue.

And your comment about cortisol today highlights the compelling logical simplicity of the model! 😂

[Tall_Allen in reply to JohnInTheMiddle]

I never heard that Zytiga blocks estradiol. Estradiol is a product of testosterone metabolism in men. So, no testosterone -> no estradiol. Estradiol is the metabolic product of the aromatase enzyme acting on testosterone. Aromatase is created by the CYP19A1 gene. Abiraterone, an androgen biosynthesis inhibitor, inhibits a completely different enzyme: 17α-hydroxylase/C17,20-lyase (CYP17)

[JohnInTheMiddle in reply to Tall_Allen]

I have to say that learning about all this is a fascinating, as a lay person of course. But the whole steroidogenesis cascade from cholesterol is amazing!

The information that you shared is very important. It's not clear to me that we disagree in any way.

Logically if we suppress testosterone, estrogen is a downstream casualty of this suppression. So it's not a direct suppression but a cascading suppression just like prednisone/cortisol.

1) Aromatase has to make estradiol from testosterone. So because Zytiga is blocking testosterone via CYP17, aromatase doesn't have any testosterone from which to make estradiol. (Zytiga is an androgen receptor pathway inhibitor after all.) I think this is what you said above.

2) We know that a side effect of some PCa therapies (e.g. Zytiga/Abiraterone as ARPI) is osteoporosis and CVD etc. and my understanding is these unfortunate side effects can be traced to low estrogen.

Can we consider then that low-dose estradiol add-back works logically in a very similar way to prednisone add-back in support of cortisol production?

And that the motivation for both is to replace hormones that are indirect casualties of PCa therapy?

(For the record, low-dose estradiol add-back should not be confused with a completely different program of very high-dose estradiol as a different kind of full-on ADT.)

P. S. - Although I have thought the above therapy adjunct looked interesting I have given up pursuing it or trying to persuade any of my doctors to do it. There may be risks.

[Tall_Allen in reply to JohnInTheMiddle]

ADT alone gets testosterone down to castrate levels.

[JohnInTheMiddle in reply to Tall_Allen]

Good point of clarification. Where does this leave us on the original low-dose estradiol question please?

[Tall_Allen in reply to JohnInTheMiddle]

I'm not following. What is the question? Perhaps PM me rather than hijack this thread.

[dhccpa in reply to Tall_Allen]

Someone will say, "Daro and Xtandi and Erleada don't block T!" But I assume their effects at least block estradiol in some way--or do they?

Thanks

[Mascouche in reply to dhccpa]

To my understanding, Xtandi is an "androgen receptor inhibitor". So it does not block production of T (like Lupron would) but it is does block the androgen receptor, which is a protein found in cells. By inhibiting the receptor, Xanti prevent androgens from binding to it. I can't say however if androgens is an all-encompassing term for just T or T andDHT and Estradiol.

[dhccpa in reply to Mascouche]

Yes, I'm not sure either way.

[Tall_Allen in reply to dhccpa]

They block T from activating the androgen receptor. Estradiol does not blockor excite the androgen receptor.

[Cali3 in reply to Tall_Allen]

TA, can you comment on this paper which talks about estradiol activating some AR mutants?

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

"In summary, out of 68 experimentally evaluated AR mutants (24 reported in the previous works and 44 presented in the current study), 25 demonstrated enhanced activation by DHT, 17 by progesterone, 12 by estradiol and 6 by hydrocortisone, compared to the wild-type receptor."

Follow up question:

Is it safe to assume that low dose estradiol add back won't cause any harm if one is on an ARI like Darolutamide or Enza because they seem to block potential estradiol activation of the AR as well?

[Tall_Allen in reply to Cali3]

Mutated ARs can be activated by anything or nothing. How is that useful to you?

Your question assumes you have a rare mutation. What makes you believe that?

[Cali3 in reply to Tall_Allen]

Since very few, if any, people get tested for AR variants, how does anyone know what mutations they have?

My question is can we assume adding back estradiol is always safe given that one may have mutations that can be activated by estradiol?

[Tall_Allen in reply to Cali3]

One doesn't select treatments based on rare mutations that one probably does not have.

[dhccpa in reply to Tall_Allen]

Follow-up. So if one is on solo Enza or Daro or Erleada (no ADT), does one produce estradiol as he normally would, since T is still produced? Thanks.

[JohnInTheMiddle]

This is astonishing Tarzan, your ChatGPT test! Outstanding test!

Can you share that prompt with us?

[JohnInTheMiddle]

Okay, because I've had interesting and even helpful results from ChatGPT, I submitted the following prompt:"If one is taking either Apalutamide or Darolutamide as a therapy drug for prostate cancer do you need to take prednisone alongside either of those drugs?"

And I got this pretty good result back from ChatGPT:

"No, you do not need to take prednisone alongside Apalutamide or Darolutamide for prostate cancer treatment. Both Apalutamide and Darolutamide are androgen receptor inhibitors used to treat prostate cancer, and their use does not typically require the concurrent administration of prednisone. This contrasts with some other prostate cancer therapies, such as abiraterone, which does require prednisone to manage side effects like mineralocorticoid excess."

And this caveat too:

"Always consult with your healthcare provider for personalized medical advice and treatment plans, as individual patient needs and treatment protocols can vary."

So now I really want to know what kind of a prompt you put 😃

[tarzantass]

Thanks for your response. The response (prednisone needed) I got from ChatGPT yesterday was so different from today’s response (prednisone not needed) . So you can tell ChatGPT’s responses are always changing.

[RoseDoc]

Prednisone is not needed with darolutamide.