After some time, Androgen Deprivation Therapy stops working and you must escalate to more toxic forms of therapy.
It is hypothesized that you can reset your cancer cells to again respond to ADT, by cycling back and forth between ADT and treatment with high levels of testosterone.
On it's surface this sounds crazy, but it can't be that crazy as there are a number of ongoing trials testing this as a treatment.
Does anyone know of any hard data supporting the effectiveness, or questioning the effectiveness of BAT therapy?
Is anyone else here considering BAT therapy? If so what are your thoughts and plans on the subject?
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I agree. I think it should be done only under very close observation, as in a clinical trial. I think they have to figure out the patient/tumor characteristics of which kind of men respond or progress. I suspect that timing has a lot to do with it - while there is a dynamic equilibrium between tumor and healthy tissue, BAT may be useful. After the tipping point is reached, BAT may be dangerous. i'm sure there are also genomic characteristics that have to be discovered.
I agree, the scope and depth of your knowledge is awesome and current. Thanks for your important contribution-makes a difference for many of us. I can’t imagine how much time you spend on these matters.
Dr. Sartor mentioned that BATcould be an option for me if the Xtandi that I've been taking for 3+ years stops working. He said sometimes it can cause it (Xtandi) to become active again.
He mentioned T therapy as a possible option to reinvigorate Xtandi I took that as BAT, I’m not at that point so I did not push for more details since he said things are changing so fast we may have new treatments to discuss in 6 months which will be at the end of October.
Hi folks, this is my first post but I thought my unfinished experience with BAT may help. I was diagnosed in 2002, had radical prostatectomy, external beam radiation, ADT (Zolodex) then bicalutamide (Casodex) which failed late last year. Everything I read suggests BAT is (fairly) safe, there is a very large population of testosterone takers out there and Morgenthaler has debunked the "testosterone is cancer fuel" thesis that still infects text books. We know it is more complicated than that, but not exactly how complicated. There are also suggestions that continuous supra physiological testosterone may work but no one has had the guts to try. In my case I thought the bicalutamide failure was the perfect time to do the experiment. Bit of a no brainer really. The best, cheapest and most accurate way to see if I was sensitive to BAT was just to do it. Most people get some benefit. Three shots of 400mg testosterone cypionate over three months doesn't do (much) damage and you go straight back on testosterone blockage if PSA progresses. I live in Australia where testosterone is heavily regulated and nobody will give it to prostate cancer patients. You have to buy it illegally on the "grey" market of locally produced stuff and inject it yourself. Bit of a learning curve there but blood tests have given me confidence in my carefully selected suppliers. Body builders are the main buyers and info source.
I waited a month after stopping bicalutamide to let it wash through. Residual bicalutamide will interfere with the testosterone getting to the cells. I started at beginning of this year. Do not take a PSA test in the first month (you will get a fright). At second month, PSA had dropped from 4.4 to 3.7, next month 3.2 where it then levelled out to a range of 3.0 to 3.2. I'm now at my seventh cycle and its looking like its just starting to increase (not by much yet, only 3.3) At the start I gradually increased the dose to 800mg but concluded there is no obvious benefit. The month before now I tried continuous dosage for two weeks at 200mg every two days. Again no clear benefit. I conclude I am moderately sensitive and the next test is when it has failed. Then I go back to my bicalutamide. I expect that to be effective for a little while (originally it failed in about a year). If it can extend bicalutamide for 9-12 months then I count it as a useful management tool for me. When that bicalutamide fails I may try another cycle of testosterone, depending on what the PSA looks like then. If not then I go cap in hand to my (horrified) ocologist.
Michael J. Morris,a,b,* Daisy Huang,b William K. Kelly,a,b Susan F. Slovin,a,b Ryan D. Stephenson,aCaitlin Eicher,a Anthony Delacruz,a Tracy Curley,a Lawrence Schwartz,c and Howard I. Schera,b
Effect of bipolar androgen therapy for asymptomatic men with castration-resistant prostate cancer: Results from a pilot clinical study
Michael T. Schweizer,*† Emmanuel S. Antonarakis, Hao Wang, A. Seun Ajiboye, Avery Spitz, Haiyi Cao, Jun Luo, Michael C. Haffner, Srinivasan Yegnasubramanian, Michael A. Carducci, Mario A. Eisenberger, John T. Isaacs, and Samuel R. Denmeade†
Bipolar androgen therapy in men with metastatic castration-resistant prostate cancer after progression on enzalutamide: an open-label, phase 2, multicohort study
I kept on the ADT all through (zolodex every three months as per normal ADT). Every 28 days I injected (intramuscular) testosterone. The testosterone peaks at about 36-48 hours and then the zolodex brings it down to near (but not quite) castrate after the 28 days. 400 mg testosterone cypionate gets my testosterone to about 50nanomole per liter, well into supraphysiological levels (high of normal range is 28). (here in Australia we use SI units) I have just started my seventh month on this regime. I'm basically following the Denmeade protocol but I did experiment briefly with higher dosage and a short period of continuous high testosterone but I saw no great change in reaction to that so have gone back to 400mg. I think Denmeade et al chose 400mg because that was the highest official US FDA approved safe dose. Body builders have been known to go to 3000mg per week. That's steroid abuse! The Denmeade protocol doesn't actually give any prolonged exposure to high testosterone - it usually declines to high normal in 4-5 days.
Incidentally I am aware that some US doctors have tried continuous supraphysiological testosterone (no ADT at all) and (anecdotally) claimed significant results. Careful monitoring required! (and guts - I chickened out at 2 weeks)
You mean you were doing ADT and testosterone at the same time?
That doesn't quite make sense to me. They each pull in the opposite direction.
I guess what you were doing was going on ADT, but generating short spikes of testosterone? And you did the testosterone spike 7 times, over 7 months, for about 36-48 hours each time?
Do I have that right?
If so, is that a protocol any of the clinical trials are using?
Yes. To all. The original "rough idea" was to induce a temporary super spike of testosterone, perhaps knocking out the castrate resistant cells which have adapted to a low testosterone environment. The pathways by which this may happen are mind bogglingly complex, but the actual effect is well demonstrated in vitro and vivo. There is still much to learn.
The protocol is fairly simple: continue ADT as normal, on day 1 inject intramuscular 400mg testosterone cypionate. This amounts to 2ml of the oil in its most commonly available form. That's all. Repeat in 28 days. etc. That is basically the operational part of the Denmeade protocol. Cease when progression is evident as an uptrend in PSA passing above the starting baseline (or before!). Try again the testosterone blocking agent that failed when it went castrate resistant (in my case bicalutamide)
This is not the magic potion. I see it as a management tool to extend the useage of of the androgen blockers (eg enzalutamide). On a very small number of men it appears to work spectacularly, and very few adverse effects on the majority but a need to monitor carefully at the start. These are after all pretty serious spikes in testosterone, given the you are starting from close to zero. Most seem to get a combination of either lower PSA or extended usage of their previous androgen blocker. Most feel better for a few days a month. There is talk of finding a genetic marker to find the most responsive men. I think the best, most accurate and cheapest test is to do it. My idea was to try it for three months and evaluate. Warning: do not do this at home!
Yes, single subject "science". There is a statistic for this, called Bayesian (learning from experience) I'm just describing my experience, not recommending. We all must do our own risk analysis. The effect on PSA was notable as at the start it was doubling every 2 months.
Perhaps my experience will help; Xtandi plus metformin plus avodart got me to undetectable but Testosterone jumped to Supra level say 1400 to 1600 range, as PSA stayed undetectable, ramped down Xtandi to just 3 per week , Testosterone staying at Supra levels - still PSA undetectable
Thanks for sharing podsart. The Xtandi (enzalutamide) would have done most of the work. So you were not on ADT at all? Here in Aus all oncologists advise to stay on ADT, even when it fails. Its the baseline treatment. Then they add androgen blockers, bicalutamide at first. Xtandi usually comes after (very expensive), often after docetaxel (a more conventional cytotoxic chemo agent).
Did you take testosterone to get to those levels? ADT works by stopping production of testosterone. But the testosterone levels are unaffected by the androgen blockers - they stop the cancer cells from taking up what little testosterone there is. The Denmeade et al initial idea was to wait until there was a large population of castrate resistant cells (after ADT and androgen blockers had failed) before hitting them with testosterone, hopefully wiping out the resistant cells and leaving cells that again respond to anti androgens. Their thinking has evolved somewhat since then as the complexities became apparent.
I am puzzled as to how you got to those testosterone levels if there was no additional testosterone introduced to your body.
My T prior to ADT was 1250 ng/dl. On ADT (estrogen patches) my T was undetectable. I went on casodex and dutasteride and now my T should go up to 2000 or more (supraphysiological). Last I measured it was only 500 but that was 3 weeks after starting this particular therapy.
Casodex stops AR conversion so increases floating testosterone. Duta stops T->DHT so increases it more. Combination should increase it 1.8-2.4x.
Seems though that casodex/duta would work opposite of what you want in high T phase of BAT.
It looks like you have a high natural level of T. I wait a month to let bicalutamide (casodex) wash through as I agree with you that androgen blockers should be avoided if you are trying to expose the cancer to high dose T. Dutasteride unfortunately has a long biological half life and takes about 6 months to wash through. I can't wait that long. But for men not doing BAT, that casodex/duta combination looks good.
On casodex/duta I felt good. Not much libido but no depression and I got a lot of strength back (estrogen therapy was great except no libido and rapid muscle loss).
I was told I had 1-2 years as the Gleason score was 5+4 and the cancer had escaped the prostate. Initially the weren’t going to do a prostectomy because they felt I was too far gone.
I was on Lupron for 2.5 years.
I went to Dr. Sartor for a 6 month check and he prescribed Androgel. His comment was he has seen me go down the tubes with no “T” and wanted me to have some quality of life, which he said that I didn’t have. I gave it considerable thought and decided to start taking testosterone gel. I can’t tell you what a difference it made in my quality of life. My “T” was 11ng/dL for several years. I became a person again. I was like the frog in the pan of water that keeps getting warmer.
This was not a BAT protocol, just something to try to make my life worth something.
Unfortunately, the PSA is rising rapidly from undetectable.
His question to me was “do you want to live 2 years with zero quality of life or live 1 year with some semblance of QOL
I am Gleason 9/10, metastatic to pelvic bone. Am a participant in the SIMCAP clinical trial whereby I have been on "standard of care" ADT multiple therapies (Zytiga, Prednisone, Eligard, Xgeva) for the last several months. PSA dropped from 20 to 0.13. I then had a robotic prostatectomy 1 month ago. Continuing on ADT (including Eligard, Zytiga, Prednisone, Xgeva) for the foreseeable future. Have also had genetic testing for determining future targeted therapies when current ones are no longer effective.
Just to clarify, did you not have a prostatectomy? Added any additional ADT therapies to Lupron?
I had RP in Oct 2011. 7.5 weeks of radiation. PSA at two weeks after RP was 2.52. 5 days later it was 3.86. RO changed the radiation schedule to be much more aggressive. Pas never dropped after radiation. Saw my Oncologist, Dr. Sartor in Feb 2012. Began 6 month injections of Eligard (Lupron) and 50mg casodex daily. Was on this for 2.5 years. No other treatment.
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Bipolar Androgen Therapy
Bipolar Androgen Therapy (BAT) and CRPC
