I am soon to start a secondary ADT drug now that Lupron is failing after 3 years. The plan is to also continue the Lupron. Why is this if it is failing? My MO says just that this has been done historically.
I have done well with Lupron, but would not side effects likely be fewer if it was stopped?
Hugh
No expert here but I think that even with rising PSA some of those cancer cells continue to be hormone sensitive and the lupron will suppress those cells. The secondary ADT (zytiga?) will hopefully address the others and bring your PSA down.
That is my understanding as well. Be aware that it is now considered OK to take a 1/4 dose of Zytiga once daily after a meal instead of taking what used to be the full dose (4 times as much) on an empty stomach.
Hi dhccpa, I'd like to know the source of your statement " it is now considered OK to take a 1/4 dose of Zytiga once daily after a meal".
I'm on Zytiga and would like to change to the 4x a day if possible.
Thanks,
Dakota Don
It was based on a study that showed it worked as well. You only take 1/4 of the old dose in total each day, after a meal instead of on an empty stomach. My local MO surprised me by proposing it although I haven't decided to start Zytiga yet. But 1/4 dose means far fewer side effects.
I found info on the Un of Chicago study:
A Un of Chicago 2017 study by Russell Szmulewitz, MD showed that: "Taking one-fourth the standard dose of a widely used drug for prostate cancer with a low-fat breakfast can be as effective and four times less expensive as taking the standard dose as recommended: on an empty stomach. The study, a multi-center, randomized, phase-II clinical trial to be presented at ASCO's 2017 Genitourinary Cancers Symposium in Orlando, FL, found that the 36 patients who took 250 milligrams of the drug with a low-fat breakfast had outcomes that were virtually identical to the 36 patients who took the standard dose, 1,000 milligrams of the drug on an empty stomach."
That's it. I had mentioned it to my main MO but he ignored me. But I saw a different one recently who brought it up on his own.
I asked my Urologist (Dr. Kwon @ Mayo) if he would comment on this study. I'll msge you if I get a reply.
Thanks,
Dakota Don
Hey Don, I saw Euge for 4 years until we had to move away. Great Doc, great guy. He and I have an interesting history together.
I tried to cut and paste but wouldn't work. It's a U Chicago study from a couple of years ago.
I'd be interested in seeing this as well. If it's from a couple years ago though, I'm surprised that it hasn't gained further traction. I'm sure the manufacturer wants to keep it at 4 a day!
Dr Kwon's reply:
Hi Mr Paul
That's a great question! We've had other patients ask about this too. Dr Kwon does not recommend a dose reduction. This clinical trial was one very small trial completed with only 36 patients so Dr Kwon does not feel it is very reliable. Unless you are having bad side effects from the medication, Dr Kwon would not recommend to reduce the dose in combination with a "low fat diet".
Best Regards
Christine, RN
Did your Doctor tell u to take one pill instead of 4 I pay out of pocket 3500 a month if I could take one a day it would last that much longer. I'll have to ask my doctor.
I have not yet gone to Zytiga. Still on Lupron only right now, although that could change anytime.
Yes i do the Lupron for my hormone in a shot plus Aberitone daily and every 6 months i do a calcium shot of some type for my bones, so if I'm correct you only take a shot different.
The cancer becomes less senstive to hormones over time and can grow with smaller amounts. It still retains dependance on hormones though so stopping Lupron will allow the cancer to take off.
The solution is add another treatment, often a second-line anti-androgen while continung Lupron. That's what I've been doing for over 2 years now. The treatments you do in addition to Lupron will change, but you always do Lupron as a baseline.
The Lupron is still working, which is why you must continue to use it. It is preventing your testes from manufacturing testosterone. Testosterone still activates the cancer, so your cancer will spread a lot more quickly if Lupron were stopped.
What has happened is that your cancer has evolved to become more sensitive than ever to even the smallest amount of testosterone or other androgens. In addition, it has evolved to prosper even without testosterone, which is why other second-line hormonal drugs have to be used now in addition to Lupron.
Thanks
Some have proposed that since Zytiga effectively blocks testosterone (and other steroid hormones) everywhere in the body, testes, adrenals and intra-tumoral, then it may not be necessary to continue “standard” ADT with LHRH drugs.
But it is not certain yet as the blockade of steroid synthesis may not be complete.
How much is enough blockade given morbidity accruing to ADT effects via other mechanisms?
That was only shown in one small trial. It requires further clinical trials. As castration resistance sets in more complete androgen blockade is necessary.
Furthermore, the D4 metabolite of Abiraterone has a further metabolite which stimulates the AR and promotes PC growth. This last step can be blocked by 5ARI like dutasterude. So why is dutasteride not commonly administered with Zytiga? -
In addition to abiraterone itself, part of the activity of the drug has been found to be due to a more potent active metabolite, δ4-abiraterone (D4A), which is formed from abiraterone by 3β-HSD.[30] D4A is an inhibitor of CYP17A1, 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase, and 5α-reductase, and has also been found to act as a competitive antagonist of the AR reportedly comparable to the potent antagonist enzalutamide.[30] However, the initial 5α-reduced metabolite of D4A, 3-keto-5α-abiraterone, is an agonist of the AR, and promotes prostate cancer progression.[31] Its formation can be blocked by the coadministration of dutasteride, a potent and selective 5α-reductase inhibitor.[31]
Because abiraterone is spectacularly effective at preventing AR activation. The lab study of a metabolite is overwhelmed by the anti-AR effect in clinical practice.
Thank you
Appreciate the detailed review of the actions of glucocorticoids and GR you recently provided.
It also contains a coherent and plausible mechanism for how switching from prednisone to Dexamethazone with Abiraterone may actually operate
A common theme in these studies has been the finding that glucocorticoids suppress or induce cytokines regulating prostate cancer growth, including transforming growth factor -β, interleukin (IL)-6 and IL-8. Glucocorticoids upregulate the antiproliferative cytokine transforming growth factor-β and its receptors in vitro, in a GR-dependent manner and mediate suppression of prostate cancer cell growth.21,22,23 IL-6 drives prostate cancer growth through AR-dependent and -independent mechanisms in prostate cancer cells.24 Exposure to dexamethasone suppresses IL-6 levels both in vitro and in patients with CRPC, potentially through disruption of nuclear factor-kappa B signaling.23,25 In these and other preclinical experiments, suppression of IL-6 blocks cell proliferation and tumor growth, suggesting that IL-6 inhibition is a potentially important mechanism for GR-mediated tumor suppression.26,27 Of interest, dexamethasone suppression of IL-6 has also been associated with decreased GR expression in vitro and in vivo, suggesting that chronic dexamethasone exposure may lead to downregulation of GR.
Are you quoting from a particular text here?
I believe that was straight out of the detailed entry on Abiraterone Acetate in Wikipedia, Pharmacology section. Surprisingly detailed en.m.wikipedia.org/wiki/Abi...
Thanks
My lupron started to not be effective after 2 and half years so adding casodex, getting 3 years on just lupron is good. I am continuing both for the future. My psa was slowly creeping up so time for a secondary defense. They do different things so go with what the dr says, go and treat yourself.
Does anyone out there know if there is a generic xtandi on the horizon? I know there is some type of generic aberaterone...
I asked this question too but got about the same reply. I guess to help keep the PSA undetectable and the T less than 20.
It has worked well so
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