Testosterone & Castration-Resistant PCa.

[pjoshea13]

New paper below.

Of great interest to me, but the full text isn't free.

-Patrick

ncbi.nlm.nih.gov/pubmed/277...

The Role of Testosterone in the Treatment of Castration-Resistant Prostate Cancer.

Drazer MW1, Stadler WM.

Author information

1From the Section of Hematology/Oncology, The University of Chicago Comprehensive Cancer Center, The University of Chicago, Chicago, IL.

Abstract

Most men with metastatic prostate cancer who are treated with androgen deprivation therapy will eventually develop castration-resistant disease. In this review, we examine the molecular mechanisms that constitute castration resistance and how these processes may be exploited using testosterone-based therapies. We detail how the utilization of superphysiologic doses of testosterone at regular intervals, followed by a rapid clearance of testosterone through continued chemical castration, also known as bipolar androgen therapy, offers an especially promising therapeutic approach. We investigate the historical basis for this modality, detail recent early-phase clinical trials that have demonstrated the feasibility and efficacy of this treatment, and describe an ongoing clinical trial comparing this modality to a currently accepted standard of care, enzalutamide, for castration-resistant prostate cancer. Finally, we explore how this treatment modality will continue to be refined in the future.

PMID: 27749326 DOI: 10.1097/PPO.0000000000000216

[PubMed - in process]

[gusgold]

Patrick,

were you able to find out the length of the on and off cycles.

Gus

[pjoshea13 in reply to gusgold]

Gus,

No luck. But the use of the term "bipolar" suggests that Stadler is piggybacking on the work of Denmeade:

"Bipolar Androgen Therapy; BAT"

"... alternating 3-month cycles of BAT and ADT. BAT was administered as intramuscular testosterone (T) cypionate or enanthate 400 mg on Days (D) 1, 29, and 57. ADT was continued throughout the study to allow rapid cycling from near castrate to supraphysiologic range T following T injections"

ncbi.nlm.nih.gov/pubmed/273...

-Patrick

[BigRich in reply to pjoshea13]

This is an interesting clinial trail. I know you are doing a form of this protocol; customized by you to fit your needs. Please keep me informed of your results, for I am interseted for my future reference.

Thank You,

Rich

[rococo]

It seems to me that flooding pc androgen receptors with T. Retards castrate resistant Ar. This happens with antiandrogen monotherapies that dramatically raise testosterone. I know this is biologicly intuitive but but some who followed this line of therapy had long survivial regardless of gleason. Just food for thought with this trickey diisease. Best luck too all

[Hidden in reply to rococo]

regardless of Gleason, or do you mean of PSA?

[Hidden in reply to rococo]

"This happens with antiandrogen monotherapies that dramatically raise testosterone."

What monotherapieS are you referring to?

[Hidden]

BAT - bipolar androgen therapy. yea. I am very interested in it as well.

[Hidden]

$50.00 hmmm. maybe wont buy just yet.

[Hidden]

and this out of Johns Hopkins, second author Antonarakis, of V7 fame.

ncbi.nlm.nih.gov/pubmed/255...

[Hidden]

and look at the authors of this study (ignore the topic)

ncbi.nlm.nih.gov/pubmed/251...

look at the guys who are colaborating:

"Nadal R1, Zhang Z, Rahman H, Schweizer MT, Denmeade SR, Paller CJ, Carducci MA, Eisenberger MA, Antonarakis ES"

Antonarakis - check

Denmeade - check

Schweizer - check

The other guys must be something as well.

[Hidden]

oops. My mistake. Confused "Schweizer" with the second author on the first paper in this thread. Got too excited. They must be at the U of Chicago, and these guys are (all) at Johns Hopkins. (another guess that I could have checked before I hit enter)

[efsculpt]

Here is what I have on Bipolar- it mentions the John's Hopkins study

fredhutch.org/en/news/cente...

[Hidden in reply to efsculpt]

yes. thanks. it gets me depressed.

so much effort and cash spent on zero T, as the core of therapy.

At the most obvious, the mindless administration of another 3-month of Eligard without testing T levels. On autopilot. It's like Payne Stewart's last plane ride.

[Hidden]

I just finished 5 months of BAT at JH. PSA went up never down, from 4 to 50 finally, and T levels were not always tested, but when it was, did not reach castrate levels. Generally 100-150.

Upon going back to roswell, they wanted me to nadir again, which I was not happy about, as it seemed a pointless delay. Catch-22. As if I was maybe cured.

So attempting to find another trial of interest in the meantime.