Been on Lupron, Xgeva ADT + Abi +P for 2 years, PSA and T unmeasurable. for most of this time. Taking only 500 x 1 Zytiga daily w/o food (convinced ONC to continue test dose that worked) + 10 mg Prednisone that has lots of my suspect SE's associated.
SE's were few and manageable but last couple months a couple dozen of others intermittently raise their heads. Main ones fatigue, memory, weakness, solid sleep are becoming difficult, and getting me ground down. Would love a drug holiday break to help sort these out, mostly restarting exercise.
Has anyone with mCSPC received a holiday. Not much, if any, in literature, and that is negativish. Starting conditions, duration, ending condition and treatment would be good to know, what argument to get it worked and how you felt about it all. Want to ask Onc, but not much ammo around.
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iADT is confusing because literature addressing it is for cases that are no longer responding to ADT but have become Castrate or Hormone resistant. If I read it right, they therefore don't address mCSPC holidays
BTW I'm off Xgeva for a cycle because of a tooth infection and risk ONJ.
That's my problem. I've responded to ADT and been at its nadir for 18+ months so I'm apparently still mCSPC, but the SE's are really getting me down. Why shouldn't I get a holiday to get exercise, R & R? Even a month or two? Some older papers liked that, and it may be worth whatever the risk, you've explained as the same as not taking enough of an antibiotic. If it simply sets me back a few months, it should be worth it.
Hi TA. I’ve read your blog re IADT vs CADT Very thorough. Great work!
One question. Has there been any study comparing the relative risks of IADT vs CADT since the doublet (and later the triplet) therapies became the standard of care? If all of these studies involve men who were only using ADT, then it seems like men who have engaged in doublet or triplet therapies are pretty much flying blind as to how IADT vs CADT may play out for them, no?
1. When one has previously done just ADT, what we've learned from these trials is that iADT makes no difference in time to castration-resistance (CR). We have to reject the hypothesis that resistance can be delayed by breaks in hormone therapy. Reducing the volume of cancer has a bigger effect than reducing the adaptive pressure periodically. Intensifying the cell kill rates with ARSi and/or chemo is known to have a bigger effect than ADT alone. What then is the oncological advantage in taking breaks?
2. IADT may lead to a 10% reduction in survival. Maybe the risk is less (between 0-10%) if the "on-therapy" cycles include an ARSi. Maybe the risk is greater than 10% because the cancer cells being given a break are even more resistant. Maybe it makes no difference.
3. I have seen no data on the effect of previous ARSi on Testosterone recovery. I would guess that it makes no difference because they don't affect the hypothalamic-pituitary-testicular axis.
“Maybe the risk is less (between 0-10%) if the "on-therapy" cycles include an ARSi. Maybe the risk is greater than 10% because the cancer cells being given a break are even more resistant. Maybe it makes no difference.”
You could even make the argument that there is a chance that the inclusion of ARSi in the “on therapy” cycles could result in longer survival times with IADT. That’s my point. With no study based upon the new SOC protocols, we are flying blind. I assume you know of no ongoing studies that compare IADT with CADT where ARSi is being used? I would guess that survival times have increased so much since adding ARSi, that such a study would take many years to determine any increase or decrease in survival times.
"You could even make the argument that there is a chance that the inclusion of ARSi in the “on therapy” cycles could result in longer survival times with IADT. "
That is exactly what I addressed in"1."
1. When one has previously done just ADT, what we've learned from these trials is that iADT makes no difference in time to castration-resistance (CR). We have to reject the hypothesis that resistance can be delayed by breaks in hormone therapy. Reducing the volume of cancer has a bigger effect than reducing the adaptive pressure periodically. Intensifying the cell kill rates with ARSi and/or chemo is known to have a bigger effect than ADT alone. What then is the oncological advantage in taking breaks?
I'm looking at this "Current Clinical Aspects of Androgen Deprivation Therapy for Locally Advanced and Metastatic Prostate Cancer: A Scoping Review for Urologists and Medical Providers - Jordan G Kassab, et al, 2024.
1. It does show the advantages which include a holiday from ADT effects some of which are annoying or serious and burdensome, or more.
2. It tabulates no great difference in iADT and ADT mortality.
3. Not mentioned in the paper, but seen elsewhere T recovery is a flip of the coin
There are gaps in knowledge that can be closed. Given it has been used successfully it shouldn't be shadows banned by no mention in a SOC. We've seen members here with successful holiday stories.
"... Taking only 500 x 1 Zytiga daily w/o food (convinced ONC to continue test dose that worked) + 10 mg Prednisone..."
That is unusual dosing. I would think that 500 mg Zytiga, which is half the normal 1000 mg dose, could be too low to be effective. And that 10 mg Prednisone, which is for those who are CR taking 1000 mg Zytiga, is unnecessarily high for you. If you are still CS, and taking so little Zytiga, why not change the Prednisone to 5 mg to reduce its side effects?
It works as is. I'm an outlier, as with food is needed in India where I understand reduced dose with food has been proven. Onc. wasn't happy, but if it hadn't dropped quickly and stayed down, I would have immediately increased the dose. I've been told by his PA the therapy has worked,
First time starting in May 2017 after completing triplet therapy.
Second time starting in April this year.
The first "holiday" lasted 4+ years the first time,
This time we are six months in, uncertain about the duration.
One of my objectives in coming off treatment was to minimize the risk of resistance. Another was feeling"better."
My medical team and I had decision criteria for coming off treatment. While off treatment we would actively monitor for clinical data showing activity, labs and consult every three months.
We also had decision criteria about going back on treatment, three or more consecutive increases,, PSA between .5-1.0, image, then decide on if, when, with what and for how long. My oncologist says likely 24 months Orgovyx and Xtandi and SBRT.. I said let's wait and see what's in play at that time based on the imaging and advances brought into play by medical research.
My clinical data says high risk - GS 8, GG 4, 18 months to BCR, PSADT and PSAV. With that kind of clinical data I have seen arguments that I should be on continuous treatment.
I have chosen not to for the reasons I listed. I guess no bone or organ involvement has played in mine and my medical team's decisions.
It my prostate cancer, not yours, so my decisions may not be yours but discuss with your medical team and decide.
If you do come off, definitely consider doing the labs and consult and develop your decision criteria about clinical data that triggers going back on.
In both cases I have recovered my T fairly quickly so that's a factor in the quality of my "holidays."
It worked for (m?)HSPC. I'm working with mCSPC, which apparently hasn't been studied thoroughly for iADT, but is rejected, or discouraged, or might be allowed. Not clear because it looks like the decision was made on inconclusive studies. I suspect I'm wrong, but I would prefer not to wait until it progresses further.
I was Hormone Sensitive when following the orders of my MO at MSK, I stopped all treatments in June 2019. My PSA has remained undetectable up to my last blood draw on 9/17/24.
I think 1 of the biggest decisions for you is quality of life. You are already 84, an age many here would sign up for in a minute. After 4.5 years of lupron & abiraterone I stopped all meds in June 2022. So far so good. Still <0.01. There is an ongoing clinical trial. Read about it here:
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