Prostate Cancer Lab #56  Bipolar Androgen Therapy (BAT) -  (Emmanuel Antonarakis)
Channel: Cancer Patient Lab
Date: 07/07/2023

May 12, 2023
Discussion forum: https://community.cancerpatientlab.org/home

A complete transcript is available at: https://cancerpatientlab.circle.so/c/bipolar-androgen-therapy/prostate-cancer-lab-meeting-56-notes-bipolar-androgen-therapy-for-prostate-cancer-emmanuel-antonarakis

00:00:00 Meeting Introduction
00:02:54 Prostate Cancer Lab #56  Bipolar Androgen Therapy (BAT): A paradoxical approach  
00:03:35 Bipolar Androgen Therapy - BAT
00:06:18 First-in-Human BAT in mCRPC
00:08:29 Clinical Trial with BAT (2013-2023)
00:09:11 When is the Ideal Time to Give BAT?
00:10:35 What Are the Types of Responses to BAT?
00:13:33 Beware of Bone Scan "Flare" with BAT
00:16:42 TRANSFORMER Study
00:18:17 TRANSFORMER: PFS and OS
00:19:23 TRANSFORMER: PSA50 Response Rate
00:20:11 TRANSFORMER: Crossover (PSA50, PFS2)
00:21:19 Quality of Life
00:22:42 BAT: Effect of HRR and/or TP53 Mutations
00:23:40 BAT: Effect of HRR Mutations (e. g. BRCA2)
00:24:02 BAT: Effect of Combined Tumor Suppressor
00:25:05 Trial Design of STEP-UP Study (NCT04363104)
00:25:55 Q&A

“It's a paradox, right? Because we're giving high doses of testosterone, the thing that we have known for 60 years is the fuel for prostate cancer. How is it possible that giving the cancer its fuel in super high doses can kill the cancer?

“A lot of the genetic markers that often predict inferior prognosis, by the same token, predict superior response to BAT, which again is a paradox.

“What are the different types of responses, or lack of responses, that patients can have? And how common are these scenarios? … Each of these three scenarios occurs roughly in about 1/3 of patients that we treat with this approach.

“It's also the only type of therapy that I've ever seen when the patients come with their spouses. The spouse or the wife would have a big smile on her face after many, many years of frowning. And it's because yes, the sex drive can come back.” – Emmanuel Antonarakis

Meeting Summary
In a previous session, advanced prostate cancer patient Bryce Olson shared the story of his exceptional response to Bipolar Androgen Therapy (BAT), where high doses of testosterone are alternated with androgen deprivation therapy. Then Bob Gatenby, MD, commented on Bryce’s experience and strategy from his perspective as a leader in adaptive therapy -- using evolutionary and game theory to inform cancer treatment strategy. Super patient Russ Hollyer has been self-administering BAT and has written a book about it.

What Does It Take to Choose BAT?
- First, most patients and oncologists are not aware of or considering BAT as an option. Pharma won’t push this treatment that only costs $200.
- Second, the patient has to be brave enough – taking testosterone can be like throwing gasoline on the fire, feeding cancer growth. 
- Third, the patient must find a doctor who is willing to support it.

An Update on Bipolar Androgen Therapy (BAT) for Prostate Cancer from Dr. Emmanuel Antonarakis
Emmanuel Antonarakis, MD, is uniquely qualified to update us on bipolar androgen therapy for advanced prostate cancer. He is the Clark Endowed Professor of Medicine and Associate Director of Translational Research, Masonic Cancer Center, at the University of Minnesota Medical School. Dr. Antonarakis is a genitourinary medical oncologist with a particular focus on recurrent and advanced prostate cancer. He conducts clinical and translational studies to bring new therapies to patients with prostate cancer. In particular, he is interested in developing novel androgen-directed therapies, genetically-targeted therapies, and immunotherapies for men with recurrent or advanced prostate cancer, and using germline and tumor genomics to inform precision oncology approaches for these patients. He also has an interest in liquid biomarker development, including the clinical validation of the AR-V7 marker as well as DNA repair markers and their therapeutic implications.

How do people typically respond to bipolar androgen therapy?
Responses are roughly divided into thirds: 1/3 will see a marked improvement in their PSA and a reduction in cancer, 1/3 will see a PSA plateau (no progression = a benefit), and 1/3 will see an increase in PSA and in cancer growth.

PSA is a rough marker. Scans and genetic tests should be performed to monitor therapeutic action. Sometimes PSA will increase but cancer scans show no growth or even regression.

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