Bipolar androgen therapy (BAT): A patient's guide

[madman]

Abstract

Bipolar androgen therapy (BAT) is a new treatment concept for men whose prostate cancer has become resistant to standard hormone‐blocking therapy. Over the past decade, we have performed a series of clinical studies testing BAT in asymptomatic men with castration‐resistant prostate cancer. The key findings from these clinical studies are that BAT (a) can be safely administered to asymptomatic patients with metastatic castrate‐resistant prostate cancer; (b) does not produce symptomatic disease progression; (c) produces sustained prostate‐specific antigen and objective responses in 30%–40% of patients; and (d) can resensitize and prolong response to subsequent antiandrogen therapy. The concept of BAT has generated significant interest from men with prostate cancer, their families, and their physicians. Here we provide a “Patient's Guide” that answers questions about BAT in a form that is accessible to patients, their families, and physicians. Our goal is to provide information to help patients make the most informed decisions they can regarding their prostate cancer treatment.




2 | WHAT IS HORMONE THERAPY FOR ADVANCED PROSTATE CANCER?

2.1 | Hormone therapy
2.2 | How does hormone therapy work?
2.3 | Why does prostate cancer become castration resistant?
2.4 | What is BAT?
2.5 | How was BAT discovered?
2.6 | How does BAT work?
2.7 | Who should not get BAT?
2.8 | How safe is BAT?
2.9 | What are effects of BAT on QOL in men with CRPC?
2.11 | How effective is BAT for metastatic CRPC?
2.12 | Can BAT restore sensitivity to hormone‐ blocking therapy?
2.13 | what does BAT cost?
2.14 | What are the future studies planned for BAT?




3 | CONCLUSIONS

The key findings from these clinical studies are that BAT (a) can be safely administered to asymptomatic patients with metastatic CRPC; (b) does not produce symptomatic disease progression; (c) produces sustained PSA and objective responses in 30‐40% of patients and (d) can resensitize and prolong response to subsequent antiandrogen therapy. Patients need to remember that BAT is not FDA‐approved therapy, does not work for everyone, and is not without risk. It is important for physicians not to overpromise results from BAT on quality of life and sexual function.




4 | WHAT ARE OUR RECOMMENDATIONS FOR BAT?

 

[madman]

5 | BAT CLINICAL PEARLS

*BAT is given as an intramuscular injection of testosterone cypionate every 28 days.

*BAT should only be given to patients with castrate‐resistant (NOT hormone‐sensitive) prostate cancer.

*BAT should NOT be given to prostate cancer patients with cancer‐related bone pain.

*BAT should not be given to patients with urinary obstruction due to enlarged prostate or prostate cancer.

*BAT should be given together with ongoing ADT or surgical castration.

*BAT may be continued despite PSA elevation, if there is clinical benefit and stable scans showing no progression.

*BAT should not be combined with Zytiga, Xtandi, Erleada, or Nubeqa (or with taxane chemotherapy).

*BAT may render CRPC patients sensitive to Zytiga or Xtandi after ADT or after prior progression on these drugs

*BAT should preferentially be administered in the context of a clinical trial, especially when being used in conjunction with other experimental therapies.

 

[madman]

FIGURE 1 (A) Androgen receptor (AR) “glove” and androgen “ball” come together in the prostate cancer cell to function. (B) Androgen deprivation involves getting rid of the androgen ball by shutting off the production of testosterone. Testosterone can also be blocked by chemicals called antiandrogens that are ball‐shaped “oranges” that prevent testosterone from binding in the pocket of the AR glove. Antiandrogens include bicalutamide (Casodex), nilutamide (Nilandron), enzalutamide (Xtandi), apalutamide (Erleada), and darolutamide (Nubeqa). PSA, prostate‐specific antigen. [Color figure can be viewed at wileyonlinelibrary.com]

 

[madman]

FIGURE 2 Prostate cancer is initially highly sensitive to ADT. (1) AR levels in castration‐sensitive prostate cancer cells are relatively low. Androgen receptor “glove” is bound to androgen “ball.” (2) Androgen deprivation removes androgen, leaving receptor empty. This produces an initial beneficial effect: PSA levels drop, symptoms improve, and the tumor shrinks. (3) The surviving prostate cancer cells then enter a dormant phase. Then they begin to increase production of levels of the androgen receptor “glove.” (4) Eventually, these cells reach a “sweet spot” where they have made enough glove to start growing again despite low testosterone levels in the blood. At this point prostate cancer cells are considered castration‐resistant. How can we shake up the cancer? (5) BAT floods the system with androgen “balls” resulting in too much AR bound to androgen, moving the prostate cancer cell away from the “sweet‐spot” and inducing growth inhibition and prostate cancer cell death. ADT, androgen deprivation therapy; AR, androgen receptor; BAT, bipolar androgen therapy; PSA, prostate‐specific antigen. [Color figure can be viewed at wileyonlinelibrary.com]

 

[madman]

FIGURE 3 Bipolar androgen therapy involves rapid oscillation of blood testosterone levels between the polar extremes of supraphysiologic (>1000 ng/dl) to near castrate (~100 ng/dl) levels over a 28‐day cycle. [Color figure can be viewed at wileyonlinelibrary.com]

 

[madman]

FIGURE 4 (A) Human prostate cancer cells growing in the lab are growth inhibited by 50% when exposed to testosterone (orange bar) while Xtandi (gray bar) has no effect on growth compared to no treatment (blue bar). Despite a 50% decrease in cell number, testosterone‐treated cells increase production of PSA by 3.5‐fold (orange bar) compared to untreated cells (blue bar). While Xtandi has no effect on growth of cells it reduces PSA production by >90% (gray bar). (B) Three patterns of PSA response in representative patients treated with BAT. These three patterns include those with “PSA response,” those with stable disease (“PSA plateau”), and those with “PSA progression.” BAT, bipolar androgen therapy; PSA, prostate‐specific antigen. [Color figure can be viewed at wileyonlinelibrary.com]

 

[madman]

FIGURE 5 PSA and CT scan (inset) response in lymph nodes in patient receiving 18 cycles of BAT on the pilot study. BAT, bipolar androgen therapy; CT, computed tomography; PSA, prostate‐specific antigen. [Color figure can be viewed at wileyonlinelibrary.com]

 

[madman]

FIGURE 6 Repeat cycling between high and low levels of androgen receptor (AR) activity by either blocking androgens or giving supraphysiologic testosterone (BAT) may be a new therapeutic approach that takes advantage of prostate cancer cell ability to adapt to changing testosterone levels in the environment. [Color figure can be viewed at wileyonlinelibrary.com]

 

[madman]

This needs to be stressed!

*The key findings from these clinical studies are that BAT (a) can be safely administered to asymptomatic patients with metastatic CRPC; (b) does not produce symptomatic disease progression; (c) produces sustained PSA and objective responses in 30‐40% of patients and (d) can resensitize and prolong response to subsequent antiandrogen therapy.


* Patients need to remember that BAT is not FDA‐approved therapy, does not work for everyone, and is not without risk. It is important for physicians not to overpromise results from BAT on quality of life and sexual function.

 

[madman]

Prostate Cancer: Bipolar Androgen Therapy (BAT)

Summary Prostate Cancer Lab #56 focuses on Bipolar Androgen Therapy (BAT) as a potential treatment for castration-resistant prostate cancer. The therapy involves alternating between high-dose testosterone injections and the continuation of testosterone-suppressing drugs. BAT has shown positive...

www.excelmale.com

 

[madman]

Dr. Sam R. Denmeade, MD - Baltimore, MD - Medical Oncology - Book an Appointment

Find information about and book an appointment with Dr. Sam R. Denmeade, MD in Baltimore, MD. Specialties: Medical Oncology.

www.hopkinsmedicine.org