Bipolar Androgen Therapy Yields Promising Results in Prostate Cancer

Bipolar Androgen Therapy Yields Promising Results in Prostate Cancer

Bipolar androgen therapy, where the body is alternately flooded with and starved of testosterone, is safe and effective for the treatment of metastatic prostate cancer, according to a study presented at the 28th Symposium on Molecular Targets and Cancer Therapeutics in Munich, Germany.

The researchers, led by Samuel Denmeade, MD, professor of oncology at Johns Hopkins University School of Medicine in Baltimore, presented results from 47 men with metastatic prostate cancer resistant to chemical or surgical treatment who have completed at least three cycles of bipolar androgen therapy.

For the study, RESTORE (NCT02090114), the researchers injected a high dose of testosterone (400 mg) into the muscle of the men every 28 days. The men continued to receive luteinizing hormone-releasing hormone (LHRH) agonist therapy to inhibit their natural testosterone production, but stopped treatment with the anti-cancer drugs Zytiga (abiraterone) and Xtandi (enzalutamide) that inhibit androgen receptor signaling, against which they had developed resistance.

“Our goal is to shock the cancer cells by exposing them rapidly to very high, followed by very low, levels of testosterone in the blood,” Denmeade said in a press release.

The first arm of the study looked at 30 men who were treated with testosterone after their disease became resistant to Xtandi and started to progress. The results showed the levels of prostate specific antigen (PSA) declined in about 40% of the patients. This decline was more than 50% in 30% of the patients.

In addition, the disease progression was halted in several patients for more than a year. In some patients, the size of the tumor decreased. In one case, PSA levels dropped to zero after three months and have remained at that level for 22 cycles of treatment.

In the second arm of the study 17 of the 30 patients whose disease had started to progress again after treatment with Zytiga, received testosterone. PSA levels also dropped in this group. In six patients, the levels of a protein associated with resistance to treatment with Xtandi dropped to zero, and two patients had 50% or more decline in PSA levels.

“We think the results are unexpected and exciting,” Denmeade said. “We are still in the early stages of figuring out how this works and how to incorporate it into the treatment paradigm for prostate cancer.”

“The benefits of the treatment are particularly evident in men who have had no sexual function for many years due to impotence caused by hormone deprivation. These men are quite happy with the new treatment,” he added. “Other positives include increase in muscle strength, increased energy and decreased fatigue. This does not occur in every man and we are not sure exactly why.”

The treatment was well-tolerated by all men. One patient reported an increase in pain and one had urine retention problems.

According to the researchers, more research is needed to fully understand the effect of bipolar androgen therapy. Denmeade warned that testosterone treatment definitely can worsen pain in men with prostate cancer who have pain from their disease.

“This therapy should only be given to men who are asymptomatic,” he said.

A second trial called TRANSFORMER (NCT02286921) is testing bipolar androgen therapy in men with metastatic castrate-resistant prostate cancer whose disease had progressed after being treated with Zytiga.

Traditionally, prostate cancer has been treated by lowering the levels of testosterone because it was thought that testosterone induced tumor growth. But according to Denmeade, there is no evidence that testosterone promotes cancer.

“Indeed, earlier research in prostate cancer cell lines has shown that treatment with high doses of testosterone could inhibit growth and kill cancer cells,” he said. “The exact mechanism is not known and there may be many things happening since the androgen receptor is the key signaling pathway in prostate cancer.”

Denmeade added that previous research in his laboratory has shown that “testosterone interferes with part of the cell division process in cancer cells called DNA licensing and also makes breaks in the DNA of tumor cells, causing them to die.”

Jean-Charles Soria, PhD, of the Institut Gustave Roussy in France and the chair of the scientific committee for the symposium, said the use of testosterone in men with castration-resistant prostate cancer “is an intriguing concept that was previously advocated some years ago, but this is the first time we have clinical data in patients whose disease has progressed after treatment with [Zytiga] or [Xtandi].”

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Özge has a MSc. in Molecular Genetics from the University of Leicester and a PhD in Developmental Biology from Queen Mary University of London. She worked as a Post-doctoral Research Associate at the University of Leicester for six years in the field of Behavioural Neurology before moving into science communication. She worked as the Research Communication Officer at a London based charity for almost two years.
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15 comments

  1. Herschell Atkinson says:

    How can I get this information to my Doctor directly. I fit most of these conditions and am on Xtandi now and PSA is back down to 0.47 for now. I am just looking to the future when the Xtandi stops working.
    Thank you for your help, Herschell

    • Jim Davidson says:

      I became resistant to both Casodex and Xtandi. 24 weeks of chemo was a waste of time (except it made my hair curly – a definite improvement). I followed that with several months of a clinical trial. I watched as my cancer beyond my bones to my livers. What finally worked was a combination Opdivo and medical marijuana taken as suppositories. My PSA dropped from 318 down to 0.34. All but three of the 20+ tumors in my liver dissolved. Opdivo worked because I had amplified PD-L1 receptors (>80%). The THC in the marijuana binded to the CB2 receptors on the cancer causing aptopsis and amplifying Opdivo’s T-cell immune response. Moral of the story: There are always options. Even when your three months away from death.

      • Herschell Atkinson says:

        Thanks Jim. It was not clear to me if you tried the BAT or if you went straight to the Opdivo (which I have never heard of) and marijuana?
        Good luck with your treatment,

      • Herschell Atkinson says:

        Good morning Jim.
        Would you mind sharing the information on your doctor and the facility where you are getting this last treatment,i.e. The Opdivo and marijuana.
        I have a very close friend who just found out yesterday that his liver is involved and he is very depressed.
        Would appreciate any information you feel comfortable sharing.
        Thanks, Herschell

          • Arne Json says:

            Hello from Sweden Jim, i read about your treatment for advanced PC and got very interested…Im 56 and failed Casodex, just started Xtandi and responding ok…my cancer is seen i 2 lymhnodes…thats the only thing seen on a PET-CT…i had surgery in 2007 and radiation…but no chemo so far…so i guess the Opdivo or Keytuda is further down the line, just want to ask you how you got to take the PD-L1 test…was it just a blood test or how is it done?. Is the combination with medical maijurana important? Hope this reaches you Jim, and i hope to hear from you soon. Best regards//Arne Johansson

      • paul fasoli says:

        very interesting…..my psa was on the rise….I stopped casadex and finasteride , because it tears your body apart.took it for three years, psa started to rise after off hormone therapy for one year, to 4.5, took cannabis suppositories for one month…psa went to 1.5.
        thanks for reassuring me of my method,i will look into opdivo.
        look into apple cider vinegar enemas. kills candida, kills cancer, they are finding cancer is a fungus, apple cider vinegar kills fungus. regards

  2. Mike King says:

    Hello world…Bless you all! I received my 1st shot of testosterone (400mg) on Tuesday 3/28/2017 @ Johns Hopkins in Baltimore, Md. This the transformer study. On Wednesday afternoon, day two, back spasms of excruciating pain developed in my back…feels like the muscles that wrap around the rib cage in my back. I am hurting as I type! Took 2.5 advil…alternating heat and ice. Hot tub helps some! Difficult to relax! Breathing can be painful as well when spasms are pain level 10 on 1 to 10! Called JHH yesterday 3/30! We shall monitor! Pain becomes more severe in afternoon. I am 65 years old…diagnosed in December 2008. Open to suggestions for spasms! Good luck to all!

    • paul fasoli says:

      hi mike, for spasms I would try calcium. magnesium , and zinc, all in one tab, also hot, cold treatment, and quinine sulphate pills or their is quinine in quinine water.
      do you have a tele number for activity doing bap…would like to look into. thank you

    • John Phillipe says:

      Mike, I am considering the BAT Therapy in the future. How are you responding? How are your muscle spasms ?

  3. Stephen B. Strum, MD, FACP says:

    I am a medical oncologist with 34 years in the field of PC (prostate cancer). I can appreciated these messages but they seem to be all over the proverbial playing field.
    PD (programmed death)-1 receptors are determined by tissue biopsy and not by blood. IHC (Immunohistochemistry) is usually the lab technique used to identify Programmed cell death protein 1 (PD-1) and the substances that interact with PD-1 (i.e., ligands PD-L1 and PD-L2). These proteins play a role in causing an immunosuppressive tumor microenvironment. Commercially available agents used to INHIBIT these proteins are called checkpoint inhibitors & include ipilimumab (Yervoy®), pembrolizumab (Keytruda®) & nivolumab (Opdivo®). There are scant articles on the clinical use of these agents in PC, and of those published so far, the results are not startling. So it is with keen interest that I read the comment on nivolumab (Opdivo®) inducing a major response. The dose & scheduling should be shared on this site. However, this thread is SUPPOSEDLY about bipolar androgen therapy (BAT) & not about checkpoint inhibitor therapy. It would have been “nice” to Jim Davidson to relate the specifics of his treatment in his email & not via facebook (of course this is my opinion). And there is nothing in the peer-reviewed literature as recently as a few months ago on the value of any form of cannabis be it THC, cannabidiol (CBD) or any other metabolite on prostate cancer in humans. That so far is all hearsay.

    • Max says:

      status
      diagnosis 2007, radiotherapy 2008, Lucrin Hormonreduction 1 year
      T2b, PSA 5,6, 12 needles with cancer, Gleason 4+4
      after treatment: psa 0.5
      recitif 2017, April 2017 1.8, means p.m. 0.1 progression
      what is to do?

    • Dan says:

      Thank You Dr Strum!
      Was there a recent article, with Dr Beer anouncing amazing activity with Keytruda. Is it only people who express pd1 or pdl1 that respond to Keytruda

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