Apaludamide help with fatigue better drug?

[Nite-owl]

Has anyone decreased appaludamide because of fatigue ? Is there another drug that doesn’t t cause as much fatigue?

[Hidden]

Darolutamide is a new anti-androgen that does not have the level of fatigue associated with other anti-androgens. That's because it has negligible blood-brain barrier penetration and low binding afinity for γ-aminobutyric acid type A receptors (GABA AR).23,27. See article below:

urotoday.com/journal/everyd...

The benefits of apalutamide and enzalutamide were found to be durable with longer follow-up of patients enrolled in SPARTAN and PROSPER.16-19 However, both drugs were also associated with an increase in certain adverse events of clinical relevance for AR antagonist therapy, including fatigue, cognitive impairment, seizures, falls, fractures, and hypertension.11,12,20 This has clinical implications because patients with advanced prostate cancer often have comorbidities and are often at increased risk of frailty or dementia.21 There is a need for effective treatments for highrisk nmCRPC that either avoid or mitigate the adverse events of interest associated with AR antagonist therapy.

Overview of Darolutamide

Darolutamide is a nonsteroidal oral 1:1 mixture of two pharmacologically active diastereomers, ORM-16497 and ORM-16555, which interconvert via their major metabolite, ODM-1534.22 Like enzalutamide and apalutamide, darolutamide binds the AR, which prevents its nuclear translocation and subsequent regulation of androgen-responsive genes.23,24 However, darolutamide has a distinct chemical structure that does not resemble the molecular structures of either enzalutamide nor apalutamide. In preclinical studies, it demonstrated robust activity against both wild-type AR and AR mutations, such as AR F876L, which may be associated with enzalutamide and apalutamide resistance, and W741L and T877A, which are associated with bicalutamide and hydroxyflutamide resistance. 23,25,26

Importantly, and presumably due to its molecular polarity, darolutamide has demonstrated negligible blood-brain barrier penetration and thus a low binding affinity for γ-aminobutyric acid type A receptors (GABA AR).23,27 In an in vivo murine study, brain concentrations of carbon-14-radiolabeled darolutamide approached the lower limit of quantification and were approximately 26-fold and 46-fold lower than the respective brain concentrations of 14-C-apalutamide and 14-C-enzalutamide.27

[Magnus1964]

Try casodex, it is an older ADT drug with less side effects

[ARIES29 in reply to Magnus1964]

Less side effects? My side effects were- Headaches, man boobs & lack of sleep due to headaches. But everybody is different.

[mklc]

Can you advise which of these 2nd generation drugs is heart friendly. I have heart problems caused by using Lupron. Thank you so much.

[Hidden in reply to mklc]

I read your bio. You've been at this game for some time. If I read your bio correctly, you've had lupron and Casodex plus something else that I'm not familiar with. Not important.

All of the 2nd line ADT have their issues and using the responses from this forum as a guide, I don't think you'll be able to determine if one is better than the other. I do think you should try zytiga first though. It has a different action than xtandi, which I believe is a more powerful Casodex. You might even discuss chemo, ie docetaxel. From what I read on this site, the SEs are similar in effect, although different than zytiga. You can then start adt right after the chemo.

The emerging trends in treatment is to hit it hard when the burden is low.

I hope this helps. And I expect you'll get additional responses over the next several days.

Regardless. Best of luck with

The next treatment(s)

[mklc in reply to Hidden]

Thank you most sincerely. I wish you great health.