Self-Experiments to Control Prostate Cancer- Using Bipolar Androgen Therapy

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madman

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*Russ’s book with detailed explanations, references, and programs is at: Amazon.com: Adaptive Bipolar Androgen Therapy (BAT) for Prostate Cancer eBook: Hollyer, Russ: Kindle Store. Free for Kindle Unlimited. Otherwise the Amazon minimum charge of $2.
 
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madman

Super Moderator


 

Guided_by_Voices

Well-Known Member
Very interesting. This concept has been known for almost ten years now I think so it's great to see it getting some traction. It will be interesting to see if BAT on a preventative basis for high-risk men gets any traction. Also good to see him bringing some IMO well-deserved attention to NPP. Hopefully it will become officially available in more locations, although this is a great example of medical progress having to happen outside of official channels.
 

madman

Super Moderator
Very interesting. This concept has been known for almost ten years now I think so it's great to see it getting some traction. It will be interesting to see if BAT on a preventative basis for high-risk men gets any traction. Also good to see him bringing some IMO well-deserved attention to NPP. Hopefully it will become officially available in more locations, although this is a great example of medical progress having to happen outside of official channels.

That would be 2010.

The first patient treated with BAT was in 2013.

The paper was published in 2015.




Effect of bipolar androgen therapy for asymptomatic men with castration-resistant prostate cancer: Results from a pilot clinical study (2015)
Michael T. Schweizer*,†, Emmanuel S. Antonarakis, Hao Wang, A. Seun Ajiboye, AverySpitz, Haiyi Cao, Jun Luo, Michael C. Haffner, Srinivasan Yegnasubramanian, Michael A.Carducci, Mario A. Eisenberger, John T. Isaacs, and Samuel R. Denmeade†

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Bipolar Androgen Therapy: The Rationale for Rapid Cycling of Supraphysiologic Androgen/Ablation in Men With Castration-Resistant Prostate Cancer (2010)
Samuel R. Denmeade* and John T. Isaacs


Abstract

Androgen ablation is highly effective palliative therapy for metastatic prostate cancer but eventually all men relapse. New findings demonstrating that androgen receptor (AR) expression continues in androgen-ablated patients has resulted in the classification “Castration-Resistant Prostate Cancer” (CRPC) and has led to the development of new second-line “anti-ligand” hormonal agents. In this background is the paradoxical observation that the growth of some AR-expressing “androgen sensitive” human prostate cancer cells can be inhibited by supraphysiologic levels of androgens. This response may be due to effects of high-dose androgen on inhibiting relicensing of DNA in cells expressing high levels of AR. It may also be due to recently described effects of androgen in inducing double-strand DNA breaks. Based on available preclinical data described in this review demonstrating the effects of supraphysiologic levels of testosterone on inhibition of growth of CRPC xenografts, we initiated a clinical trial in men with CRPC testing the effect of monthly treatments with an intramuscular (IM) depot injection of testosterone. This IM formulation achieves supraphysiologic levels of testosterone that cannot be achieved with standard testosterone gel-based applications. The supraphysiologic testosterone level is followed by a rapid drop to castrate levels of testosterone with each cycle of therapy. This “bipolar androgen therapy” will not allow time for prostate cancer cells to adapt their AR expression in response to environmental conditions. The goal is to determine if a clinical response can be achieved through this non-adaptive rapid cycling approach in men with CRPC.




CONCLUSIONS

The available preclinical data suggest that a subset of CRPC may respond to treatment with androgen. This response may be due to effects of high-dose androgen on inhibiting relicensing of DNA in cells expressing high levels of AR. It may also be due to recently described effects of androgen in inducing double-strand DNA breaks which may result in either growth inhibition or activation of cell death. The published clinical data demonstrate that testosterone can be administered to men with CRPC and low disease burden. The studies did not demonstrate significant clinical responses, suggesting that administration of testosterone to achieve physiologic testosterone levels is, by itself, not sufficient to achieve a clinical effect in men with CRPC. Based on animal data showing effects of supraphysiologic levels of testosterone on inhibiting growth of castrate-resistant prostate cancer xenografts, we have initiated a clinical trial in men with CRPC with rising PSA and minimal metastatic disease (≤5 sites of disease) testing the effect of “bipolar androgen therapy.” In this approach, men with CRPC remain on castrating therapy but also receive monthly treatments with an IM depot injection of testosterone. This IM formulation achieves supraphysiologic levels of testosterone that cannot be achieved with standard testosterone gel-based applications. This high-dose serum testosterone level is followed by a rapid drop to castrate levels of testosterone with each cycle of therapy. Concurrent with the testosterone injection, men will receive oral etoposide based on laboratory findings showing the ability of etoposide to augment and stabilize androgen-induced DNA double-strand breaks. Additional laboratory studies are underway to assess the effect of combinations of other inhibitors of DNA repair with androgen in an attempt to identify promising regimens that can be tested in clinical trials.
 

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