How long can you be on Xtandi?

@thanasis, what helps you manage the fatigue and headaches?

My father is 91. With stage 4 metastasized prostate cancer since 2021 when diagnosed. His original PSA level was over 2,600. He has been on xtandi and zoladex and xgevia since 2021. Minimal side effects. PSA got as low as undetectable. But has slowly started to creep up to .84. Is on his 4 treatment of Pluvicto. Still hanging in there with minimal side effects. Mostly, fatigue. I know each person is different.

But hang in there. There are so many different options available now. Find out what works best for you.

One year later and Xtandi ("X candy") is just another friend.

I feel so good now that I'm going to have a hip replacement next week.

@bluegill Yes, ditto for Erleada with me nearing the end of my 5th year.

Side effects like brain fog are rare with all the -lutamides, but they must be nasty when they happen.

There's never been an actual head-to-head trial to confirm which -lutamide is least likely to cause those cognitive side-effects (there are competing marketing claims for Erleada and Nubeqa based on the slim evidence of a restrospective human study and experiments on mice, respectively), but the majority won't experience them on any of the three.

@northoftheborder
At yesterday’s PCF online meeting about the ASCO Conference they discussed the difference between Darolutamide and Enzalutamide When it comes to brain fog. Darolutamide was much better and that also applies to apalutamide They specifically brought up the fact that Darolutamide doesn’t pass the blood brain barrier like the other two drugs. It’s a study called ARACOG. Here is a slide from that talk.

@jeffmarc That's good news -- it will be interesting to see the results when ARACOG is complete (it has just finished enrolling participants).
https://clinicaltrials.gov/study/NCT04335682
Note that it will be a head-to-head only against Enzalutamide (not Apalutamide), based on reported symptoms, and that it will be open label (so the participants and their doctors will know which one they're getting).

As for now, all we know is that Darolutamide didn't seem to pass the blood-brain barrier in mice in early tests. The impact on humans remains hypothetical, though ARACOG should add more certainty.

@northoftheborder
During the intro from PCF, they specifically said that Darolutamide doesn’t pass the blood brain barrier. The test results they had, already showed that Darolutamide caused fewer brain issues. Sort of interesting they mentioned getting lost in a parking lot they were familiar with. I’ve never even faintly felt that problem. My wife has that problem and she’s not on any drugs.

Another interesting thing. Many people switched from Enzalutamide to Darolutamide, But no one switched the other way.

@jeffmarc Yes, you're right. The clinicaltrials.gov page shows the trial as still in progress, but it appears that ARACOG has just presented its findings, and while patients on both Enzalutamide and Darolutamide showed a decline in cognitive test scores, the decline was greater on average with Enzalutamide. Also, the patients on Darolutamide eventually got better at the test with repetition (they remembered how it worked and gamed it a bit), while the patients on Enzalutamide did not.

It might also be comforting to know that the absolute risk is low across the board.

Even in the "worst" case — ADT + Enzalutamide — over 91% of patients experienced no cognitive impairment. For ADT + Apalutamide, over 95% experienced no cognitive impairment, and for ADT + Abiraterone, it's over 96%. ADT + Darolutamide exhibited little increase over ADT alone (a bit over 97% had no cognitive impairment in either case), but also, they note that there was only one relevant study for Darolutamide at the time (2024):
https://dailynews.ascopubs.org/do/mental-health-and-cognitive-toxicities-androgen-receptor-signaling-inhibitors