Monotherapy or ADT3?

[Frigataflyer]

Hola Friends, I need advice concerning Lupron as a Monotherapy or switching to ADT(3) as suggested by Maack C (2019). Triple Hormonal Blockade (ADT3): A Patient’s Perspective. Oncogen Journal 2(1): 6.

Maack says: “ Anyone moved to androgen deprivation therapy, and particularly anyone with already known advanced and metastasized prostate cancer SHOULD NOT be prescribed only a GnRH agonist or antagonist as monotherapy.”

My current urologist says I likely have metastasizes and I have been told the same story by two other urologists, my GP and an alternate medicine physician. They were all reacting to my initial PSA > 150ng/dl. My gammagram in June 2018 showed no mets. Since then I have had a biopsy (Gleason 9).

My current urologist started me on Casodex in December and a month later in January he switched me to Lupron.

The Casodex knocked my PSA down to 33. The PSA and Total Testosterone Values at one month intervals following my first Lupron Shot were:

Feb

PSA...2.7.....Total Testosterone...17ng/dl

Mar

PSA...1.3.....Total Testosterone...6ng/dl

Apr

PSA...0.9.....Total Testosterone...<10ng/dl

I just returned to my Home in Mexico about 3 months plus 3 weeks after first Lupron. I immediately visited the urologist and he told me that ADT3 therapy was a waste of money and to continue with Lupron as a Monotherapy.

I would greatly appreciate the opinions of group members about going to ADT(3) or remaining on Lupron as a monotherapy!!!!

I have a related observation/question.

For the first 2 months of my Lupron shot, I felt lousy but well before the end of the three month Lupron period, I felt more like my old self. I had more energy, less brain fog, less muscle/joint soreness and even had a few indications that Mr. Dick would like a little attention. I assume this to be the result of my three month shot wearing off. Now that I am three weeks “late” for my second shot I feel normal.

I am not a masochist, but I am wondering if using “feeling normal” is a better indicator of need for another Lupron shot than a rigid three month calendar. The three month suggestion is obviously an average response. But whatever the rational for three month intervals, there is a variance around that mean and perhaps I come from the end of the distribution that meets the criterion for needing another shot at two and a half months. Any thoughts here? Thank you for listening and everything else you guys and gals do for this group.

David

[Tall_Allen]

Casodex usually adds little to Lupron and there’s no evidence that Avodart adds anything at all. Unless you’re adding a major second line hormonal or T with Lupron doesn’t get below 20, I don’t see evidence for any advantage to ADT3

[Darryl Partner]

Rarely do I comment. Chuck Maacks article is an opinion piece by a lay person printed in a pay to play journal. Just use it as a question provoker.

[Frigataflyer in reply to Darryl]

Tall Allen and Darryl, thanks for your replies. Does this mean that Maack is incorrect in stating:

“Triple-hormonal blockade/androgen deprivation therapy (ADT3) includes the prescribing of a GnRH agonist or antagonist (I use LHRH and GnRH in the following but in reality, either is appropriate for agonists) to shut down testicular testosterone production; an antiandrogen to block testosterone access to the cancer cell nucleus; and a 5Alpha Reductase (5AR) inhibitor to prevent any testosterone that might access the cancer cell nucleus from converting to dihydrotestosterone/DHT.”

He states that there is “significant” evidence, but fails to supply any references. However, Later in his paper he does cite some of the physicians, who, I have come to believe, are considered heavy hitters.

He quotes Dr. Myers November 2009 “Prostate Forum” newsletter:

“However, in our clinic, I go further. There are two forms of androgen in men: testosterone and dihydrotestosterone. There is broad agreement that dihydrotestosterone is 10 times more powerful than testosterone in stimulating the growth of prostate cells. There is now also powerful epidemiological, laboratory, and clinical trial data showing that dihydrotestosterone is important in the development and progression of prostate cancer. With this in mind, starting in 1995 I made it a standard practice to also check dihydrotestosterone levels in men on hormonal therapy. I have been surprised by the number of men who have castrate levels of serum testosterone who have serum dihydrotestosterone levels within normal ranges. If dihydrotestosterone is 10 times more powerful, then these men have enough androgen to impair response to hormonal therapy. I think this provides strong support for the use of triple hormonal blockade (addition of Proscar or Avodart) in men with elevated dihydrotestosterone levels. However, I must stress that my views on dihydrotestosterone and the use of Proscar or Avodart are not accepted by many in the prostate cancer field. Nevertheless, I am not the only one who thinks dihydrotestosterone is important. In fact, the major public advocates of this approach are (Medical Oncologists) Stephen Strum and Robert Leibowitz, who have both focused on the development of triple hormonal blockade that includes blockade of dihydrotestosterone production.”

Later he cites Dr. Strum: “ADT should be at least ADT with 3 drugs to include anti-androgen (AA) e.g. Ca-sodex or Flutamide (Note: or Nilutamide/Nilandron) followed one week later by a GnRH agonist like Lupron or Trelstar or Eligard. I also use Avodart along with the anti-androgen (AA).

Although Maack’s paper, in a “vanity publication,” is dated 2019, the referenced work of Myers and Strum appears to be 10 years old. Does that mean that the field has moved on but Maack, who appears to be elderly, has not?

I will get my dihydrotestosterone checked and if it is “normal,” as opposed to my almost neglible total testosterone, then I will start thinking more about Avodart?

[tango65 in reply to Frigataflyer]

Perhaps you will be interested in these studies:

onlinelibrary.wiley.com/doi...

ncbi.nlm.nih.gov/pubmed/108...

ncbi.nlm.nih.gov/pmc/articl...

[Frigataflyer in reply to tango65]

I read everything, sometimes several times. Don’t always understand. Thank you

[Schwah in reply to tango65]

Wow one thing stuck out in your third link :”No clear survival advantage has been observed with the use of ADT in men with metastatic disease...”. Please tell me I’m not on this stuff for nothing? Hopefully more recent studies have debunked that ?

Schwah

[Hidden in reply to Schwah]

I clearly believe that without ADT I would not be here today...

[AlanMeyer]

First of all, your intuition that feeling better was a bad sign may well be correct. I suggest getting your testosterone and PSA levels tested before the next Lupron injection. If your testosterone is above 20 ng/dl, you've probably gone too long.

Secondly, it seems to me that, given your Gleason and PSA scores at diagnosis, your cancer is aggressive enough to warrant combination therapy.

I don't know if ADT3 is effective or not. Some doctors, especially including Dr. Robert Liebowitz, claimed very significant benefits for it. One study (prostatecancerinfolink.net/... put some numbers out to say that it was not, but the study had too few enrollees to draw statistically significant conclusions, and there were questions raised about the dosages. However some very high powered studies (CHAARTED and LATITUDE) showed a very convincing improvement in lifespan when ADT is combined with chemotherapy or Zytiga. See Tall_Allen's summary of the trials at: pcnrv.blogspot.com/search/l... .

Best of luck.

Alan

[Frigataflyer]

Alan, Many thanks. I think my intuition is correct on this. I am going to try to develop some measures, so I can maybe identify the turning point of when the Lupron level is getting “thin”. My first measure is one that came to me last week and it concerns “brain fog” as follows. Last week when I was staying up until midnight, full of energy, etc. I noticed that the time between forgetting something and then remembering what it was that I had forgotten, seemed to be dropping. I only forgot things for hours or a few days. To me that seemed pretty easy to quantify, so I am going to diarize that during this next course of Lupron.

Thanks again

David

[Frigataflyer in reply to Frigataflyer]

Alan, just made my first pass through paper you referenced above. Thanks

[Frigataflyer]

Brilliant! I like “natural” and I am already taking a few of the supplements turned up in my Googling of, what turned out to be, the “hair loss” data base. And, w/o figuring out how pubmed works, I am going to add a few more. That said, I know there is a recent post on using Pubmed and I will at least get into some of the research that, I expect, supports this industry.

[GP24]

Instead of ADT3, the current recommendation is to add Zytiga to ADT for high risk patients:

medscape.com/viewarticle/91...

[john205]

The best evidence available currently, from much later than 2009, is that there is benefit from Lupron plus either abiraterone (another form of ADT that acts on the adrenals) or docetaxel (a form of chemotherapy). Either one adds about 1 1/2 years to survival, on average. There is no current evidence that triple therapy of any kind provides benefit in a man who is still responding to either of those 2-drug combinations. When either of those combinations stop working, then other treatment may be added. Have you seen an oncologist? They have access to treatment other than ADT that may be available to you now (like docetaxel) or later on when there is resistance to Lupron.

Regarding side-effects of Lupron, that appears to be variable between different people. Make sure you remain as active as you can - regular exercise really helps with fatigue, even something a simple as walking for an hour of so every day. Watch out for weight gain. A good balanced diet and protecting ideal weight range within normal BMI also helps. As far as intervals between Lupron doses, if your testosterone level is still down, it's working, unless your PSA is rising. Please strongly consider seeing an oncologist if you haven't already.

[bobdc6]

Urologist? Maybe you need an oncologist.

[RonnyBaby]

I believe you need more time for the Lupron to work fully.

It took 10 months for my PSA count to get to the nadir (lowest point).

The triple blockade, at this point in time, seems like overkill, in my humble opinion.

And the added cost(s) and potential side effects could be unnecessary.

Note that my G score was at 9 and my PSA started above 300 - today, I'm undetectable.

Get a second opinion .....

[JimVanHorn]

Getting back to basics, just remember that androgen deprivation therapy (ADT) negatively effects the production of testosterone and other androgens. It does not "Kill" cancer cells. It does slow way down the reproduction of cancer prostate cells. So the cell eventually is killed by the immune system or dies of old age. In a burning building it is best to close all of the doors. It doesn't do any good to run through the building and close them all again. With PCa some members are ADT resistant and other agents can be used 2 or 3 at a time. I had PCa for 11 years, with 72 radiations, and Eligard injections every 3 months. I no longer have cancer. I wish you the best in your therapy and remember to just keep truckin'.

[GeorgeGlass]

425 days vs 623 days was the difference in the TARP study so adt3 is probably now effective but what after the side effects of adt3, are they worse than just lupron?