ADT Side Effects & Different ADT Drugs
My brother-in-law has recurrent prostate cancer (he was originally diagnosed with stage 4a) and his oncologist wants him back on ADT drug he took for 2 years. Thing is the side effects were horrendous. From what I've read (NCI, ACS, etc.), side effects can vary some between the various ADT drugs. His oncologist said they all have the same effects.
What I'm wondering is if anyone else has had bad reactions to an ADT drug and tried another with and and few and/or less troubling side effects.
Comments
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Hi,
From what others have stated the ADT side effects vary from person to person and you probably won’t know until he is on the drug for a while. If he had a bad reaction to the previous ADT drug, then maybe choose another one. There are several out on the market, he should discuss with his doctor.
Dave 3+4
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Thanks much for the reply, Clevelandguy!
Yes, I've understood that there's variability from person-to-person in terms of side effects. And I agree that he won't know what any side effects will be until he tries a specific med and finds out. And I'm aware, as stated, that there are a number of ADT drugs available.
The question, however, still remains: Have folks who have tired more than one ADT drug found that one drug has fewer or less severe side effects than another. It's a given that everyone's experience will likely vary. All I'm trying to ascertain is if others have found there to be a difference in terms of side effects using different ADT drugs.
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My radiologist at Dana Farber felt that the best way to alleviate side effects of hormone therapy is to be physically fit heading in and working hard during to maintain. Muscle loss is a real factor as testosterone disappears, keeping up resistance training will avoid the worse.
Eric1 -
I am new to this board, and it occurs to me that I am actually doing this experiment currently. Once diagnosed with a high-risk grade4 PCa, I switched to Penn Med and my RadOnc guy there prefers the lupron shots (extended release, quarterly injections) over my previous ADT drug, Orgovyx (oral, daily). So I stopped Orgovyx and started Lupron this week. Will report back with my anecdotal experience.
- Dave
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Dave's point is of interest with respect to side effects.
Orgovyx is taken once daily as a pill.
Lupron is injected once every month, 3 months or 6 months. This has to be done 'just so' and patients have reported side effects just from the injection.
In conclusion, the statement of the oncologist that these drugs all have the same effects is grossing over important issues. In other words, the side effects reported by patients vary considerably (as Clevelandguy already pointed out).
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Thanks, Old Salt. That was my understanding as well. My bro-in-law (just bro from now on) is going to seek a second opinion. His oncologist has consistently had a lackadaisical attitude…sigh.
And I guess I misunderstood Clevelandguy (sorry!). I had thought he meant that effects vary from person-to-person while taking the same drug, which the oncologist acknowledged.
Anyway, it definitely will be a good idea to get that 2nd opinion…
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@Angstromm Although I'm not on ADT, I've done plenty of research in anticipation of being put on it one day. Like your bro, I am also experiencing a recurrence, but it's too early to do anything about it yet. I remain on active surveillance with quarterly blood tests.
There might not be much difference in side effects experienced by the same person between the different medications within a family of ADT drugs, for example Lupron vs. Zoladex in the case of LHRH agonists, but there can be a huge difference in side effects between the different families of ADT drugs. By that, I mean that if treatment was in the form of an anti-androgen such as Casodex taken as a monotherapy instead of an agonist like Lupron for example, the patient would experience far fewer sexual side effects and hot flashes and also maintain bone density, but might feel nauseous and might need to accept having breasts. Another family of hormone treatment, via good old-fashioned estrogen (Estradiol) will also minimize or eliminate the nasty side effects of the agonists and actually improve cognitive function compared to 'normal' men including the ability to multi-task! But it's feminizing effects may not be tolerable for some.
I firmly believe that every patient should be able to make an informed decision to take whatever drug suits their tolerance for certain side effects. For example, I dread hot flashes and cognitive issues, and if I had a choice I would select a drug that minimized those side effects, but unfortunately not every country permits the use of every different option.
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@OnJourney - This is an excellent point. These drugs have very different MOAs, but while making this choice (I already have) Im wondering about possible negative effects of direct AR antagonism in the early stages of PCa. Are any biochemists out there who can answer this question:
"Do anti-androgens (ie AR antagonists) drive the PCa to CRPC transition?".
I'm an old G-protein receptor guy and when you directly antagonize a GPCR, it can usually find a way around this blockade by increasing receptor and related signaling components' levels and activities. Does this happen with nuclear receptors? In PCa? Does it drive CRPC? Is any of this known?
Again, Im very new to this and am educating myself as we go, but isnt the transition to CRPC what we really want to prevent (postpone)?
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You are correct. Antiandrogens can lead to adaptation of PCa's antiandrogens receptors.
The old bicalutamide (casodex) was made of a similar biostructure of the real androgen to assure that it would be absorbed/get stuck at the cell's receptors, but after extended periods of use, the AAWR (antiandrogen withdrawal response) occurred, showing that at some time, the bandit start feeding on the bicalutamide itself. The PSA would decrease significantly once stopping the antiandrogen.
In regards to ADT castration resistant occurrences, it starts when the bandit becomes independent of the testosterone for survival. It starts feeding on other androgens (for instance dihydrotestosterone) or even producing the means of survival by itself. Our body protection system doesn't recognize cancer as a bad thing. It will defende the cancerous cell from anything we throw at it. Darwin principle. (If interested you can read one of my old post on the matter)
The newer breed of antiandrogens called "androgen receptor signaling inhibitor" works differently and has shown more affinity sticking the mouth of the cancer, making it difficult of surviving. In other words, it provides some relieve to patients experiencing castration resistant PCa.
I am on apalutamide together with ADT (Eligard) due to a bone metastasis. My PSA is in remission levels. Hopefully it will maintain that status for one year when I plant to start my vacations off-drugs.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468615/
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OK … Im back with my anecdotal experiences with Orgovyx (GnRH antagonist, daily, oral) and Lupron (LHR agonist, quarterly injection). I was on each medication for 30d with Orgovyx first. My biopsy showed a high-risk PCa, and I switched docs to go with a very good cancer center nearby (Abramson - PennMed). There I received my first Lupron shot following an HDR brachytherapy boost.
The side effects of these drugs seemed about the same to me. My testosterone is now <20, or undetectable, and I am experiencing hot flashes, feel more lethargic, no libido at all, and even possible cognitive effects (feel a little "foggier"). So for me, the side effect profiles of each ADT therapy will not dictate my choice, as they are so similar. They both suck.
Please note that both of these are ADT testosterone lowering drugs, and as pointed out by others, a direct AR antagonist like Casodex or Enzalutamide should not lower testosterone levels and may provide a much different, and better side-effect profile. As I mentioned above, I am still concerned that the direct antagonism of the AR could drive the PCa to CRPC transition. I am looking into this more.
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I've been on Lupron plus Zytiga/Prednisone for a bit over a year, with another to go (plus started with RPS and then RT to regional lymph nodes). I had all the side effects mentioned, including having osteoporosis (so am also on Zometa). I say "had" because I just recently started the lowest dose Estradiol patch (0.025mg) and after about 2 weeks, the hot flashes vanished. I also am less fatigued. It should also help with bone loss, but if I see that on my next DEXA, I won't know whether it was that, the Zometa, or a combination. Search for the PATCH study, and papers by Russell and Grossmann.
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I’ve been on Casodex daily with a Lupron shot quarterly for 9 years. Am Stage 4, but as long as this combo works, I’ll stay on it. Side effects were stronger earlier, lessened over time. What began as a trial is now commonplace. Happily other newer drugs await any failure!
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Thanks for sharing your experience, paulguenette. Would you mind saying more about the change in side effects: how long and how bad were they at first and how long did it take for them to taper off?
Thanks again!
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initially the side effects were irritating. Hot flushes for which I was given an Rx kind of tapered off in 6 months to a year. I lost body hair including on arms and legs, no buggy. There was some energy lost, some lethargy increased, but I remained active and fought that off. One benefit is loss of body odor.”; no longer need or use deodorant! I tell people I have the body of a 10 year-old. My Gleason 10 Stage 4 prostate cancer is being controlled.
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So glad for you that your cancer is being controlled! Advancements in prostate cancer treatment have been pretty amazing! And thanks again for the reply…
My bro-in-law and dear friend has stage 4a and is doing well—PSAs are where they should be. While he was on ADT (don't know which drug) his side-effects were terrible and his energy level plummeted to the point where he wanted to stop treatment (TX). He managed to finish his course of TX, though, and his energy has gradually returned. I think his big concern is that if/when his cancer returns will he be able to find a course of treatment that won't rob him of so much energy and enjoyment of life.
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Oncologists should certainly try a different med that most likely won’t have such drastic side effects. Medicine should help not hurt!
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In my humble opinion, the meds aren't the major cause of side effects.
The meds stop testosterone production and the lack of testosterone is what causes the major side effects.
It has been a year (next month) since my last Lupron injection. My testosterone has NOT recovered and I continue to have annoying side effects. At my age (77) the docs are saying it may take a LONG time for the testosterone to recover or I may need testosterone replacement therapy to get back to normal.
I also blamed the meds but, sadly, I feel they all have similar major side effects - caused by the lack of testosterone.
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Yes, to the above post but be aware of the fact that different individuals may have different experiences while their T is low. Some have reported major side effects, others more minor. Mine were (sort of) in the middle, but as has been pointed out repeatedly, exercise does help.
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