I'm not knowledgeable enough to answer your question but I will offer some ideas that may or may not be useful.
Zytiga is a drug that blocks the synthesis of testosterone (T) in the body. It interferes directly with the biochemical pathway that is part of the process of synthesizing T from precursor chemicals. It works very differently from Lupron which, as I understand it, does not directly block synthesis, but rather overloads and thereby inactivates the chemical signaling that tells the testes to produce T.
Your profile page says that, at one time your T level went down to 0.03 on Lupron and Casodex. If the scale for that is ng/dl (the usual scale used in the U.S.) that is an extraordinarily low value. I can't remember anyone posting a number that low before. If that number is accurate and is in ng/dl and is still where you are, then it's hard to see what role Zytiga could play in knocking down T any further. So I'm thinking that, if the number really is that low and is still that low on this 4th intermittent cycle, maybe Zytiga won't do anything useful, just add side effects.
If your PSA goes up in spite of the Lupron + Casodex that you're on then there are a number of things worth trying. One that used to be very common was to discontinue the Casodex which, counter-intuitively has enabled some men to drop their PSA. Another is to try something stronger than Casodex at blocking T uptake, like Xtandi. Once the PSA goes up in spite of the Lupron, it's time to start trying things. Until then, I have some doubts, especially since you appear to have no evidence of metastasis yet.
My opinion isn't authoritative. Perhaps no one's is. There's too much we don't yet know about prostate cancer and there are many differences between patients based on particular mutations that can occur in their DNA. Furthermore, I'm not sure I have a good picture of your full situation. I had thought you were non-metastatic but in a later post you said you were known to be metastatic. Your initial PSA at the time of diagnosis might give a lot of information about that - though I haven't seen what that was yet. But for whatever it's worth, here are some thoughts on your situation.
First of all, you've had a very good run on intermittent ADT, but I think that's over now. It's my impression that most men who do well on ADT only do well for a maximum of four sessions and three is more common. I think it's probably best to assume that you'll be on continuous treatment from now on and that a period off treatment now would do harm and shouldn't be done.
I also think it's likely that you're coming to the point where other treatments besides Lupron and Casodex are needed. You might start by cutting out the Casodex in line with gregg57's observation that cancer can adapt to Casodex and actually be increased rather than decreased by it. I don't think that most men experience a PSA drop after dropping Casodex, but some definitely do. It could be worth trying but you'd want to monitor the PSA frequently to be sure that something good is happening and not something bad.
If I understood him correctly, Tall_Allen thought that a trial of Zytiga is worthwhile. I can say without qualification that Tall_Allen knows more about this stuff than I do and I think he knows more than some oncologists do too. I take his ideas very seriously. Zytiga might be worth a shot. Are you sure that your T level is 0.03 nanograms / deciliter? If it is, I don't know why Zytiga would work, but if your T level is higher than that, then maybe it will work. It's my understanding that one of the ways that PCa adapts to hormone therapy is by greatly increasing its sensitivity to T. It multiplies the number of T receptors it produces and extracts even the tiniest amounts to signal cancer growth. So even when your T is very, very low, it's possible that lowering it still further can hold off the cancer for another period.
Other advanced hormone therapies are also possible including Xtandi and the new darolutamide. In addition to those treatments there are others that might be worth trying. One that seems plausible to me is chemotherapy with docetaxel. It works on an entirely different principle from all of the hormone therapies and may work for men who have completely exhausted hormonal options. Maybe Provenge is a possibility.
You should also consider whether your medical oncologist is an expert in prostate cancer. There are hundreds of different kinds of cancer and no oncologist can master them all. You want a doctor who really keeps up with prostate cancer research and can fully understand what's happening to you as well as anyone can.
This doesn't sound very encouraging does it? However I believe that there's an excellent chance that you still have some years to go and that you can get a lot out of that time.
Thank you Alan for putting my situation in perspective in such a complicated field
On my 3rd cycle I did stop cassodex though on lupron and my psa did go up
My mo put me back on cassodex and the psa did go to undetectable
Though it took about 6 months
My testerone is almost at nothing
I did stop cassodex so will see in 4 weeks what the number is
Very grateful for you and everyone for taking the time and concern to give me advise
It is much needed
Good health to everyone
Casodex can eventually become an agonist and feed the prostate cancer. One way to tell that is to stop and see if the PSA declines.
You said your PSA is doubling every 5 weeks, but it's curently .01? If that's the case, I would keep going until it gets above 2, then consider other options. You also have Xtandi or Enzalutamide. That's like Casodex on steroids without the actual steroids. It's about 5 times more effective as Casodex.
Hi Christopher’s, my understanding is drugs like bicalutamide are first generation antiandrogens and Abiraterone, Enzalutamide, and Appalutamide are second generation and are an improvement over first generation drugs. That is, second generation antiandrogens are basically more effective drugs. There may be situations where the first gen drugs could be used effectively, but your MO can probably help you with the decision.
Using Zytiga as part of intermittent ADT for recurrent (but not yet detectably metastatic) PC has been explored in a randomized clinical trial. One group of recurrent men got 8 months of Zytiga+ADT; the other group got 8 months of ADT alone. The group that got Zytiga were able to stay PSA-free for longer. Moreover, testosterone recovery was not delayed by the Zytiga treatment, and the time to PSA relapse after testosterone recovery was delayed among those randomized to Zytiga.
To me, the advantage of early systemic therapy with Zytiga is that it may kill cancer cells that have not yet formed significant PSA-generating tumors. Remember that PSA is mostly generated by tumors that have grown big enough to generate their own blood supply, so just having undectable PSA doesn't tell you the whole story. By killing more of the micrometastases, early Zytiga may increase survival.
tall allen: but this study doesn't seem to answer the question: is casodex or zytiga "better" with Lupron. Casodex has no significant side effects for me, but Zytiga is reported to have a whole range of side effects. That needs to be considered, too.
There may be options: a-lower dose zytiga, b. dexamethasone instead of prednison, c. I don't know how much prednisone with low dose zytiga. The problems with prednisone seem to be manageable. For many the benefits will outweigh the risks. Good luck.
Unfortunately, drugs that are more effective usually come with more side effects. If you take nothing in addition to Lupron, you will incur no extra side effects, but your survival will be shorter.
Hi herb, check out the ENZAMET trial. It showed that Enzalutamide is a more effective inhibitor of the androgen receptor that bicalutamide. You would have to extrapolate the results to Zytiga, but my MO thought it was okay to extrapolate to Zytiga if I understood her correctly. Then there’s the side effect component that needs to be considered. But my MO thinks Zytiga is superior to bicalutamide. Would be a good way to frame the question to your MO by referring them to the ENZAMET trial.
Dan, in my case I don't think so. I had triple bypass, a long history of heart disease and I live alone. Zytiga seems to be a particular problem for cardio patients; Xtandi seems to have side effects that scare me more-seizures, particularly. Casodex, on the other hand? at low dose (50 mg/day) mild liver; elevated dose (150 mg/day) may be another story. With my psa hovering at 0.4 on Lupron/casodex/avodart, I plan to ride this combo as long as I can before even considering heavier antiandrogen. (PS: I'd insist on low dose Zytiga only, 250 mg/day)
Hi herb, sounds like in your case you’ve found the best alternative. I’m taking Darolutamide because of elevate liver enzymes and high blood pressure with Zytiga. With Daro my liver enzymes and BP are normal. May not be an option in your case but may be worth a conversation at some point withYour MO? My MO is telling me Daro is better than Bicalutamide. Wish you the best!
Yes. It's called "bicalutamide withdrawal syndrome." I don't know that it matters whether it is used continuously or intermittently - the AR may eventually feed on it either way.
Sorry- I'm not following you. Does what make the second generation drugs less effective? The RCT I linked to shows that Zytiga + ADT is more effective than ADT alone on an intermittent protocol.
I was using Trelstar and after my last vacation in 2018 and sbrt tx I switched to estradiol patches in 2019. Psa is undetectable. Ask your doc about that since the only side effect is gynecomastia.
Milk the casodex for all it's worth. It is an older drug with less side effects. I get suspicious of doctors that want to stop a drug that is working. Just my paranoia about motive being money. The newer drugs are more expensive and the drug companies wanting to get all they can out of the price till the patent ends.
Do doctors get paid from the drugs they prescribe? I would think it makes no difference to a doctor ( in terms of finantial incentive) what they writes on the prescription paper. Am I being naive?
I was on Casodex for 5 years. Then 5 years later went on zytiga. Zytiga lasted 3 1/2 years as did xtandi. Your doctor is feeding you a line. Milk the Casodex for all it's worth. Admittedly everyone responds differently to cancer drugs, but I don't see how he/she could make that call for you. Ask the question.
I have been on Zytiga for 2 years with undetected psa. I see your apprehension in switching. I would be upset if my physician wanted to change me unless my current regiment was not working ( either psa increasing progressively or hemoglobin lowering over 3 months) get a second opinion have a full body scan. Is your doctor experimenting? Good luck in your decision. Enjoy your family.
It’s new approach that oncologists prescribe Zyriga sooner and some researches indicates that it has positive effect and somehow castration resistance will be delayed .
I am presently on a regime that includes monthly degarelix injections ( hate the histamine response from mast cells at injection sites ) as well as daily bicalutamide oral 50 mg . I was recently switched from 4 month dose Lupron injections by my MO at Memorial Sloan Kettering due to concerns regarding my development of peripheral neuropathy of unknown etiology . Not sure if the benefits of early use of Zytiga applies to your case with your 10 year history . I do share , however , Tall Allen’s concerns about micro-metastasis . When were your last scans and what type ? ( I understand micro- metastasis are undetectable ) Be well
I would agree with Alan on this issue. I moved to Zytiga only when Casodex stopped working. My PSA went from .3 to 2.4 so my OC changed me to Zytiga. The drawback of Zytiga is they also put you on Prednisone. This causes weight gain. I went from 154lbs to 195lbs before they took me off of the Zytiga/Prednisone combo because it was not working, PSA continued to rise (3.1).
They then put me on Xtandi which had been highly recommended by several of my other doctors. Turns out I could not tolerate Xtandi and had just about every side effect listed plus some that were not listed. After 2 months they took me off Xtandi. Most side effects subsided.
For a while I was only taking the Eligard monthly along with Xgeva. The OC then got me on the program for Xofiga (Ra223). This is a 6 month program where you get the infusion once every 4 weeks. I will be getting my 3rd infusion in about a week. My PSA initially dropped from 3.8 to 2.5, but went back up to 3.2. OC says we need to go through the 6 infusions before the PSA will stabilize.
I'm very partial to zytiga since I've been on it for five years in remission with very minimal side effect I would definitely take the advice of Tall Allen he knows what he's talking about any he shows you the studies that prove it. I I'm just a little bit amazed that you said your PSA usually goes back to undetectable or usually doubles in 5 weeks because cancer any chance is so unpredictable I don't really think most people can make a blanket statement like that cuz because we don't really ever know. I think you're doing really great so far so as always I say keep the faith battle brother
Zytiga has some side effects that may be hard to be tolerated but I recommend you to take it because if you have a chance of remission by taking it ,Why shouldn’t you try?
Casodex from my Medicare part D provider is zero dollar monthly copay if it matters. Xtandi was over 13,000 annually including donut hole, Zytiga is likely very close to that,,,generic impact not considered.
Casodex may provide an excellent response even when Xtandi has failed. Possible to fact that pathways to resistance for 1st generation AR inhibitors differ from 2nd generation medications. I will leave to more informed than I to debate this phenomenon.
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