This question may be more theoretical than practical, but I am curious.
We use ADT to lower T and get a PSA response and regression of PC (and get symptom relief). Eventually ADT "fails" and PSA rises. But ADT continues to "succeed" in keeping T low, so we stay on it, since low T continues to be important to our next therapies in limiting PC progression.
Why wouldn't the same be true of abiraterone? Once abi "fails" in keeping PSA low and in preventing progression, does it not still "succeed" in its function, and still inhibit CYP17A1 and decrease the production of testosterone?
It seems if it remains important to keep T low with ADT, even after ADT fails, that it might also remain helpful to go further and continue to limit adrenal T and intra-tumoral T, after abi fails.
Now of course, abi has a significant financial cost as well as potential side effects... but then, so does standard ADT. So while I first thought, "Oh it would be too costly to keep on doing abi" I soon realized that staying on ADT isn't exactly free, either.
Other than the fact that it is not currently standard of care, are there good reasons why "Zytiga for life" would not be beneficial (or somehow be harmful) when compared to "Lupron for life?"
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Because AR internalization, intratumoral synthesis and new ligand activation have superseded abiraterone effectiveness. However, the combination with apalutamide as in the ACIS trial may be a good idea.
Suppose one was still castrate-sensitive and using abi monotherapy as his sole form of ADT. (I believe the SPARE trial showed this was feasible?) When PSA started to rise on abi, could that person continue on abi rather than switching to standard ADT? If not, why not?
Thank you for answering the main question, which I interpret as there being no point to staying with abi since its potential benefits over ADT have been nullified. But about the parenthetical part of my question -- " (or somehow be harmful)" -- I was also wondering about potential downsides with respect to progression or interference with subsequent treatments. Could it promote increased treatment resistance?
I don't disagree... but you mean chemo+enzalutamide+ADT, right? You would want to add Lupron or another ADT agent to chemo+enzalutamide as SOC, I would think.
So like I was saying, the question is less a practical one and more theoretical: while in practice you would always do chemo+enzalutamide+ADT, couldn't in theory you do chemo+enzalutamide+abi+pred?
I don't believe theory is a guide. Only empirical evidence counts. The combination of enza+abi was tried for mHSPC and found to be no more effective than either alone, but with greater toxicity.
Yes, I agree theory, generally speaking, should not guide practice when empirical evidence exists to do so. And so the idea of successful abi monotherapy, instead of abi+ADT, was a theoretical guess until the evidence from SPARE indicated potential viability of that route.
I guess what I'm asking is, if they actually did a trial following men who had failed either abi or enza (or both), and it was comparing ADT+[next therapy] versus abi+[next therapy], what do think the results might be based on existing facts and theory?
I understand this is total conjecture and probably not where you like to go, so I understand completely if you don't care to go there... but thank you for the conversation to this point!
SPARE was a small trial (34 in each arm) with only 12 months of follow-up that hasn't yet been confirmed by a larger trial. I agree it is interesting and merits further study. There was also an interesting single arm trial of enzalutamide monotherapy:
So I know this is going to be attacked as a non-SOC non-RCT unproven alternative question, but why are some of our-off-the-reservation brotherhood following the English Patch trial guidelines and using tE2 gel to drive down their T for a month or more, and then stopping application of dermal estrogen and flooding themselves with T by injection to achieve their own DIY BAT?
We know that COE facilities administering SOC guidelines will never approve tE2 use for ADT because of the litigation threat hanging over the institutions and the malpractice lawyers lurking behind the court house dumpsters, but tE2 is obtainable overseas as is testosterone. Most of us know someone who is and has been doing this procedure for sometime.
Interesting post. I am castrate and my drs still have me on Zytiga and estrogen gel. My T is <12. Not sure if that will change with my next level of treatment options, but atleast so far (6 months castrate) my Dr’s are staying the course. 🤷🏾♂️
I’ve been doing 400-800mg a day for about a year as well as Zytiga. I’ve been castrate resistant for about 6months. My scans show no progression, my AP is 85, but my psa is rising (just under doubling). Is this evidence that something’s working or am I wanting it to badly to work? Who knows.
I think this a good question. We don't say that ADT lupron has "stopped working" when we become castrate resistant and then stop using it. So why do we say that a second-line anti-androgen such as Xtandi or Zytiga has failed and should be stopped?
I think that logic is beginning to be questioned with the trials involving chemotherapy and Xtandi. From my experience, the 2 together (Cabazitaxel and Xtandi) were working better than either alone. The question should be "is it better?" rather than "Is it working?". My PSA was doubling every 3 weeks, and chemotherapy plus Xtandi didn't stop it from rising but significantly slowed things down plus provided pain relief. I'm still taking the Xtandi I have left because it's better than not taking it IMO, based on the slower progression and less pain.
I'm sure that cost is a factor in all of this too.
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Trying a high dose testosterone clinical trial 
Why should I continue with ADT ?
MO recommendations at Mayo, Moffitt?
Rising PSA after RALP MSK 8/16/18 Eastham
