ADT vacation versus Continuous

[6357axbz]

Here is a response from my MO when I asked him about intermittent vs continuous ADT.

You are right for patients with only biochemical (PSA) progression of disease, continuous did not show evidence of superiority over intermittent treatment.

For widespread metastatic disease in the bone, intermittent treatment is not feasible, because the disease progresses rapidly when we take a break from treatment.

For oligometastatic disease, I think that intermittent schedule may be practical for a minority of patients whose prostate cancer is exquisitely sensitive to ADT and who can therefore afford to take a break from treatment, because they will respond to everything and tend to do well anyway.

If you do not feel comfortable with an ADT "drug holiday", you should not do it.

According to our current understanding and from the research I am aware of, those patients who have done the best tend to respond well to standard treatments in which we treat differentiateded cancer cells (that express AR, depend on androgens, and produce PSA) and also take something else that controls the CRPCa cells (the most important of which probably comprise cancer stem cells that do not express AR, do not depend on androgens, and do not produce PSA) and will be or eventually become resistant to conventional treatments including ADT, abiraterone, and chemotherapies, etc...

You maybe interested in taking a look at prostate cancer stem cells in particular and cancer stem cells in general in our strategy to enhance current cancer treatments and in our goal to improve (exponentially rather than incrementally) overall clinical outcomes in the near future.

Best wishes and regards!

[Break60]

If you use estradiol patches instead of SOC ADT it’s easy to stay on it as long as it works !

[NPfisherman]

The jury is kind of still out there...see study below:

urotoday.com/conference-hig...

I have a friend who stopped ADT 6 months ago--one met, G7....after 15 months of ADT + Zytiga.... he stopped and in 6 months, his T came back to normal, the "brain fog" improved, and his PSA remained "undetectable"

I believe that each patient has to look at their own situation honestly....if going off ADT, then monitor closely--monthly PSA's versus q3-4 months and go back on when needed.

Another guy I know took a 1 year vacation and then went back to it before PSA became detectable...

My advice--Know your disease--Get to very low/undetectable PSA, and then decide....

Don Pescado

[Papillon2 in reply to NPfisherman]

👍

[NPfisherman]

Some last thoughts along with a meta analysis of studies:

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

If one is going to do an IADT vacation, it should be done before 24 months on ADT as the recovery of T is seriously impaired after that time period...

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

My one friend did dutasteride at conclusion of ADT and his T=560 at 3 months after 15 months of ADT...a solid recovery...and remains "undetectable" on his PSA...

I agree with Friedman that DHT is the real enemy and not T... If T is the enemy, why do some do BAT and get a remission/ significant drop in PSA ?? Perhaps T is not the "accelerant" that some people want to believe regarding PCa...

Don Pescado

[6357axbz in reply to NPfisherman]

Good info! Thanks once more Don.

[6357axbz in reply to NPfisherman]

Don,

You state, “My one friend did dutasteride at conclusion of ADT...”. Does this mean he took dutasteride immediately after stopping ADT? How muc and how long did he take dutasteride?

Thanks

[NPfisherman in reply to 6357axbz]

Not sure and he follows this site...he may come on and post here... I will ask and see what I can find and post back later or have him post--sending him a message.....his T jumped from below 20 to 560...he may have taken some supplements as well. He is another savvy fighter on this hell ship.... I believe that getting T up quickly and keeping DHT low may be the answer to longer vacations ...Here's hoping so, as that will be my plan if I take a vacation...

Don Pescado

[6357axbz in reply to NPfisherman]

Don, what do you think my MO means when he states,

“You maybe interested in taking a look at prostate cancer stem cells in particular and cancer stem cells in general in our strategy to enhance current cancer treatments and in our goal to improve (exponentially rather than incrementally) overall clinical outcomes in the near future.”

[NPfisherman in reply to 6357axbz]

6357axbz,

I believe that he is telling you to focus on prostate cancer stem cells or CTC's... It is CTC's which lead to metastasis... the primary and secondary tumor sites are not what kills... It is the release of CTC's that leads to future metastasis and death... What I harped on at APC forum in regards to SBRT for oligometastatic patients was that by getting on ADT, and in my case, Zytiga, and then having SBRT after 6-8 weeks would result in the death of primary source of CTC's--the tumors while ADT + Zytiga would help clean up CTC's...

Dr Lisanti has done animal and in vitro studies on azithromycin, doxycycline, and Vitamin C for killing off 90% of CTC's.. the abstract:

ncbi.nlm.nih.gov/pubmed/310...

Nalakrats and pjoshea13 are believers in 5 loxin inhibitor--Boswellia serrata for CTC's..

healthunlocked.com/advanced....

The good news is that they are figuring out ways to remove CTC's from the circulation. There are many issues such as micrometastasis and CTC's which are problems that need addressed to improve outcomes.

In the meantime, I am watching vaccine trials because I believe that activation of our immune systems is what will lead to cures and ultimately, prevention... The Science is coming !!!

In the meantime, eat some broccoli sprouts and have a great weekend...

Don Pescado

[6357axbz in reply to NPfisherman]

Great explanation Don! Thanks

[jdm3 in reply to 6357axbz]

I do follow this and happy to chime in now that I just got a message from Fish.

You can see my profile for treatment over the last few years. My last 3-month Lupron was November 2018, stopped Zytiga in March 2019, and tapered off the prednisone in a few weeks. In June 2019 PSA was undetectable and total T had already recovered to 560 (though Free T was relatively low). I was still anemic and tired - it takes a while to recover from the ADT even after T comes back. Those meds just wreck the body so should not be surprising that it takes months to regain balance.

I just had another test a couple weeks ago. Still undetectable (thankfully!) and T is above 700. I did not supplement with anything to get there. It definitely makes a difference in quality of life. I did not realize how tired I was until I wasn't as tired and the brain fog is slowly clearing (though my wife might not agree :-).

I started Avodart (Dutasteride) as soon as I stopped the ADT. This was on the advice of Prostate Oncology Specialists. My MO at Dana Farber Cancer Institute said "we do not prescribe that, but I don't think it will hurt." Hmmm. I started with 0.5mg every day for a few weeks and now take every other day or every third day as it has a relatively long half life. My DHT in June was very low. I do not yet have the DHT value for a hormone panel last week, but am assuming it is still low. I agree with Fish - it's important to control the DHT.

Finally, Friedman and some on this forum suggest that it's also important to monitor estradiol (E2) and keep that slightly below or around 20. Three months after ADT my E2 was 16 (probably still affected by ADT) and last week it was 32. That's too high as far as I'm concerned so now trying to figure out how to bring the E2 down a bit.

Edited to add: I think exercise is hugely important in all of this and is a factor in how well we tolerate ADT and possibly how well we might recover during IADT.

Hope that helps. Let me know if you have other questions.

All the best, Josh

[Hidden in reply to jdm3]

700? That’s a red blooded male .. congrats josh ..

[cesanon]

It would seem to me hard to justify not trying an ADT vacation.

If it works for you the benefits are undeniable.

If it doesn't work, you find out very quickly and adjust course.

I guess if you have heavy mets maybe its a different calculus. But maybe even there, then do weekly instead of monthly PSA testing.

[cujoe]

Well, I'm sort of late to the thread on this post, as I quit the APC forum some time ago and while registered here, only started reading here when I knew some others had moved here. (Some posting here know why I quit APC.) However, cesanon is right on the money from my point of view.

I consider myself to be an extreme case of non-SOC intermittent ADT - likely the result of my MO being out of the country for my post-3 mo follow-up appt after doing 3mo depot Lupron w/ biacalutamide (front-end bridge for PSA flash). Before starting initial ADT treatment my PSA had risen to +25. That was with no prostate and after 8 weeks of adjuvant IMRT about 3 years prior.

At the follow-up appt. I met with a NP who seemed somewhat clueless about SOC regime for Intermittent ADT (which I had initially agreed to do). Labs after 3 mos were 'undetectable" PSA (<0.1) and T=09. So I said: "Well, let's see what happens after 3 mos off treatment." And while I'm not sure what my MO would have said to my comment, the NP said nothing, so when I came back for my next appointment (with my MO) 3 mo later, he came in the exam room and said: "Well, you are an enigma. Your PSA is undetectable and your T is 586!" That was now 2 years ago and my PSA has remained "undetectable" (<0.1 and/or <0.064) and my T has fluctuated widely between the 586 high and a low of 190. (it is worth noting that my lowest T labs (126 & 127) were right before my RALP in 2013 and right before I went on ADT; i.e., when my PSA was highest.)

The reason I post my experience is to challenge others to question the 12-18 mo ADT "induction" phase used for IADT. While I may be a definite outlier in terms of my superior response to a single 3 mo round of ADT, unless it is tried, how would anyone else know if it can be done by others?? It may also be significant that the results of genetic testing of tissue from my final biopsy (STRATA clinical trial) showed zero defects. (Note that this test was not specific to PCa, but did include about 120 genetic defects common to it and other cancers.)

I believe by reducing the ADT "induction" phase to 3 months, I have likely preserved its effectiveness as a primary treatment for a future time by not driving the cancer to be CR. No doubt, I got a superior response to a very short ADT treatment, and that may not be the case for all PCa patients. However, with T in the age-adjusted normal range for my 72 years (and continued undetectable PSA), I can vouch for the QOL advantage I have had over these last two years. Good Luck to others, no matter what treatment protocol they follow. Be Well - cujoe

[6357axbz in reply to cujoe]

Much appreciate your comment cujoe

[NPfisherman in reply to cujoe]

Well put, my brother... glad you are here....welcome...now, if I could get Lady Margaret to consider a "vacation" , but she is scared...me too a bit because of my D2 status of metastasis.. Have a great evening....

Don Pescado

[cujoe in reply to NPfisherman]

The Don with the surname Pescado,

I understand well that my experience may be a uniquely N of 1 and that stopping any treatment that is showing a positive result involves risks - often risks that are in defiance of clinical evidence.

I had two sets of std bone and CT scans when my PSA started rising post-surgery. Neither showed any signs of metastatic disease. Had they been positive and/or I had one of the more sensitive scans with signs of metastases, I'm not sure I would have been quite so cavalier about not following a longer initial treatment regime. I am also single with no kids and a bit farther along life's highway than most, so any risks fall singularly on yours truly.

That said, I would like to think that there might be others with a similar disease profile who would have equivalent short-term results. I say short-term, since there is evidence that a scorched-earth treatment regime might have been the most prudent path for me to follow. Time is always the ultimate arbiter in such things. Be Well - cujoe

[Hidden in reply to cujoe]

You are one in a million cujoe . Keep rockin and rollin down the highway .. ✌️

[cujoe]

The pleasure is all mine. We all learn from the shared experiences of others.

[Hidden]

I was on double adt Lupron and Tak-700 a year and a half until orchiectomy . I went in to remission after RT over four years ago . No -one wants me to drop the pills . Even my naturalpathic Onocologist my holistic leader tells me to stay the course .... Iwas devasted with the side effects of adt and RT but I’m still here in a clear status . More difficult for me to vaca . I’d need to inject t .. I’m caught in adt limbo limbo limbo .. still , I’m happy to be alive . Scott