Androgen Annihilation.

[pjoshea13]

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."

-Patrick

[1] ncbi.nlm.nih.gov/pmc/articl...

[Kuanyin]

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 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.

[softwaremom00]

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)

[cesanon in reply to softwaremom00]

Dutasteride is the generic name of Avodart

[Hidden]

Thanks for this.

[cesanon]

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

healthunlocked.com/advanced...

[cigafred]

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

[pjoshea13 in reply to cigafred]

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

clinicaltrials.gov/ct2/show...

-Patrick

[cigafred in reply to pjoshea13]

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

[billyboy3]

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 in reply to billyboy3]

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