Abiraterone Withdrawal Syndrome - anyone experience it?

[Tall_Allen]

A friend of mine stopped Zytiga and his PSA went down. I'm familiar with bicalutamide withdrawal syndrome: PSA increases after a while taking Casodex but goes down when Casodex is stopped. This is caused by the Androgen Receptor using bicalutamide to become activated, and is well known. I've even seen reports of this occurring with Xtandi (see below). But Zytiga is not an antiandrogen per se -- it's an enzyme blocker, so I didn't understand how this can happen.

onlinelibrary.wiley.com/doi...

In going over my friend's PSA pattern with his oncologist, his oncologist told me he's seen it too. He said that a metabolite of abiraterone is able to act as a ligand (activator) of the androgen receptor (AR). It is a minor effect compared to the powerful androgen-suppressing effect of abiraterone. But as the AR is amplified and more mutations occur in it, it can sometimes become noticeable.

I was wondering if anyone in this forum has noticed this: PSA went down when Zytiga was stopped.

[Hidden]

Could be the related to the Glucocorticoid Receptor. There is some speculation regarding prednisone in this, but I haven't done much research on this. Here's an article:

ncbi.nlm.nih.gov/pubmed/291...

GR is significantly increased upon long-term abiraterone or enzalutamide treatment in the majority of preclinical models, thus identifying GR upregulation as an underlying mechanism for cells to bypass AR blockade.

[Tall_Allen in reply to Hidden]

Thanks. I'm not sure how glucocoticoid receptor upregulation would lead to PSA decrease when abiraterone is stopped. Are you hypothesizing that abiraterone acts as a ligand for the GR?

[Hidden in reply to Tall_Allen]

Prednisone is also stopped so I was just wondering if the increased expression of the GR from Prednisone has anything to do with it.

Here's more on that:

The known clinical benefits of glucocorticoids appear to contradict recent speculation that increased expression of GR following exposure to AR blockade may be a resistance mechanism driving CRPC. Arora et al. demonstrated that induced levels of GR are associated with resistance to enzalutamide (8). These correlations have been used to support the premise that GR upregulation can bypass the AR pathway and contribute to resistance to hormone therapies.

From:

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

[TeleGuy in reply to Hidden]

This perspective on the SWITCH trial hypothesizes three mechanisms for how prednisone could stimulate the cancer over time (paragraph 5). Withdrawing AA also involves tapering off prednisone, so I echo gregg57's suspicion that prednisone withdrawal might be at least part of the effect:

nature.com/articles/s41416-...

[Hidden in reply to TeleGuy]

Thanks for the great article. Very informative.

[6357axbz]

I reached my PSA nadir a month after beginning my ADT (lupron/abiraterone/pred) holiday.

[Tall_Allen in reply to 6357axbz]

Interesting. Did they stop your abiraterone because of that?

[6357axbz in reply to Tall_Allen]

No, I stopped abi at the same time my 6 month lupron injection expired as a planned ADT holiday. A month later my PSA (and T) was lowest ever. A month after that they started going up again.

[Tall_Allen in reply to 6357axbz]

So it sounds like it was just the residual effectiveness of the previous abi treatment that kept your PSA lower. When the abi effectiveness wore off, your PSA went up.

[6357axbz in reply to Tall_Allen]

I think so, at least when both abi and lupron wore off

[6357axbz in reply to Tall_Allen]

I’d like to think I’m not close to HR cause ADT still very effective when I stopped.

[tango65]

It has been described :

sciencedirect.com/science/a...

[tango65]

It seems that accumulation of progesterone during abiraterone treatment could be involved:

ncbi.nlm.nih.gov/pubmed/310...

[timotur]

Yes, I was on Zytiga for 5 months through HDR-BT and quit halfway through IMRT, continuing with Lupron, PSA was 0.03, fell to <0.01 one month later and remains there four months later.

[tallguy2]

Thanks for posting this!

[cbgjr]

I was on abi +lupron + xgeva together for about 4 months and the psa never dropped below 4. Then psa started to rise and abi was stopped when psa was 7.5

In two weeks without abi, psa continued to rise, after two weeks it was 9.5

So it didn’t decrease in my case.

cbgjr

[Rkoma]

TA, this guy at Yananow has lot experience with Zytiga withdrawal syndrom yananow.org/display_story.p...

Rkoma

[Peterd110]

To what extent and how long did your friend’s PSA decrease after stopping zytiga?

[Tall_Allen in reply to Peterd110]

PSA dropped for a month - I can't remember the exact PSA - something in the neighborhood of 0.5 ->0.1. Then he was able to get Nubiqa.