Androgen Annihilation.: In past posts I... - Advanced Prostate...

Advanced Prostate Cancer

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Androgen Annihilation.

pjoshea13 profile image

In past posts I have suggested that it might be prudent to include Avodart & statin when on ADT. The idea being to block backdoor androgen production. With the recent discussion of treatment-emergent, aggressive PCa variants, it seems like a good time to examine "Androgen Annihilation".

When researchers realized that the androgen receptor [AR] remains in play when ADT fails, it breathed new life into targeting the AR axis. Huggins simply hadn't gone far enough with castration. What was needed was a scorched earth approach (& hopefully the cure wouldn't kill the patient).

'Androgen Annihilation' is self-explanatory. It means total war on the AR. & it implies using multiple drugs - one for each escape route. Perhaps a cure might even be possibe? But at least a durable response? The risk being that a particularly nasty treatment-emergent variant might emerge.

For those interested in the concept, a 2014 paper by James Mohler (Roswell Park) [1] explains it well:

"Androgens may be “annihilated” using simultaneously a luteinizing hormone releasing hormone (LHRH) antagonist or agonist to inhibit testicular production of testosterone, a cytochrome P45017A1 (CYP17A1) inhibitor to diminish metabolism of testosterone via the adrenal pathway and dihydrotestosterone (DHT) via the backdoor pathway, a 5α-reductase inhibitor to diminish testosterone reduction to DHT and backdoor metabolism of progesterone substrates to DHT, and a newer anti-androgen to compete better with DHT for the androgen receptor ligand-binding domain."



11 Replies

Good review of the present arsenal. Two-an-a-half years ago, I was on Lupron, Avodart, Zytiga and Xtandi for nine months. In addition, I also took a statin and Metformin. Since then my PSA has remained stable as have PET/CAT scans. Question, based on this study which is a little dated (2015), might a discussion with my oncologist re the resumption of this regimen be warranted? Who wants to voluntarily start taking this stuff, but might it not be a good time to reduce the androgen-sensitive troops?

Kuanyin profile image
Kuanyin in reply to Kuanyin

I left out a big IF: the coverage of the combo of Xtandi and Zytiga under our current healthcare policies may no longer be possible. I was lucky taking Ketoconazole when I was first diagnosed years ago. I took it and ignored the Prednisone because I was concerned with the possible side effects!!!! What was I thinking? I did this for 18 months and never said a word to the oncologist. Luckily, I was one of a small group of people who could tolerate Ketoconazole and didn't seem to suffer any adrenal problems sans Prednisone.

Thanks for posting.. FYI: For anyone else who downloads the paper.. I think Dutasteride and Avodart are the same. (I try to highlight parts of the paper)

Dutasteride is the generic name of Avodart

Thanks for this.

This type of treatment may no longer be available to people with Medicare Advantage programs. See:

Trump Administration New Policy Authorizing and Encouraging Step Therapy

My med onc is involved with the "ANNIHILATION" trial which is similar to what you have described.

pjoshea13 profile image
pjoshea13 in reply to cigafred

"apalutamide, abiraterone acetate + prednisone, and degarelix" ?


cigafred profile image
cigafred in reply to pjoshea13

Probably, I did not pay close attention since I am not eligible.

This is the exact treatment that I have been on for 19 years and am still here, but sadly, now failing, but IT WORKS!!!-for some.

pjoshea13 profile image
pjoshea13 in reply to billyboy3

19 years for advanced PCa is impressive. I wish you many more! -Patrick

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