There may not be a lot of people that can offer anecdotal reports on both as monotherapies but the reason I ask is some studies in the last 3 years are showing administration of Xtandi during Radiotherapy has shown outcomes as good as if not better than RT + ADT.
"enzalutamide has a higher affinity to the androgen receptor, achieving a superior response in the castrate-resistant setting."
Conclusion "...enzalutamide may be as efficacious as ADT as an adjuvant treatment in combination with RT. It may be better tolerated than ADT as well."
Of note, Enzalutamide has direct radio sensitizing properties where ADT drugs only have an indirect radio sensitizing effect from lowering Testosterone.
My gut is that currentyl no insurance company would approve Xtandi for use in a Salvage RT setting for hormone-sensitive non-metastatic PCa patients because I'm assuming being a newer drug, it's expensive as hell.
However with that said, I'm curious if anyone has ever been on Ogrovyx alone and then on Xtandi alone, how they would compare the side effects they felt on each?
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The EMBARK study compared the results of Enzalutamide alone vs lupron alone vs both together for high risk BCR with non metastatic HSPC. The details of that study indicate enzalutamide alone superior to lupron alone but the combination was superior to both monotherapies. Reading the details of the study would help you see the SE profile of each group.
The HR is significantly lower on the combination, but I can imagine one feels pretty miserable on both at the same time. But I guess better to feel miserable for a few months and be alive versus dead in 5 years.
I just recently transitioned to mono enzalutimide.I'm not feeling any different than when I was on mono Eligard. Recently I've been feeling better and it's only anecdotal, but it may be due to my T returning. I'll know more if I continue to feel better and I get my next T test and it shows it returning.
I thought Xtandi is just another form of androgen deprivation therapy. They all have different pathways, but they all vector through suppression of testosterone.
It depends on your definition of androgen deprivation therapy. If defined generally, the goal is to prevent activation of androgen receptors (AR) in PCa cells. But ADT is usually defined more specifically as drugs that prevent the formation of testosterone. No T in the blood yields no activation of ARs. Xtandi is an anti-androgen and works by directly blocking the ARs, and preventing whatever T is in your system from being used.
True of 2nd gen adt Xtandi but 2nd gen Zytiga works to limit or stop T production.
Zytiga works by interrupting the androgen-making process at an important step. It inhibits androgen at 3 sources—the testes, the adrenal glands, AND the tumor itself.
Yes, Zytiga (now generic abiraterone), is a production inhibitor (ADT) rather than a receptor inhibitor (ARI). And although it is old (2011), I guess it's called 2nd Generation because it takes ADT to a higher level by inhibiting e 3 sources.
I think that the acronym "ADT" traditionally only refers to Lupron ADT (and its clones) that stop the production of testosterone by interfering with the production of LH and FSH hormones (which signal the testes to produce T.) Estrogen therapy works exactly the same way...but no one refers to it as ADT. Perhaps one should say "Estrogen ADT" instead...
Second-generation drugs, like enzalutamide (Xtandi), work by blocking the binding of Testosterone molecules (actually, DHT molecules) to the Androgen Receptors (ARs) on the prostate cancer cell. The levels of testosterone are unchanged and remain high during enzalutamide monotherapy, but the "activity" is quite low because the DHT molecules are blocked from binding to the ARs. In other words, the enzalutamide molecules bind to the ARs and subsequently block the DHT molecules from latching on.
It's like someone who jumps in line in front of you at the supermarket checkout...he/she blocks your access to the cash register.
Good day partner . Here is my story . I had PSMA PET SCAN done on October the 4-th and it showed that in the bed of the prostate which I had removed 2002 now there is new growth an the mets have spread around .in the pelvic . Since November I am on hormonal treatment with Xtandi and a imlant in my stomach of RESELIGO 10.8 mg . Both these drugs are to lower my PSA which went up to 150.5 in a short ime after I had COVID-19 2020 . In three months the PSA came down to 55.5 which was hard to believe and it made me happy including the Doctors . Then this month I got sick with the flu and my PSA went up to 76.8 in one month . Now here is the problem with the drugs on me . First three months I as OK but a few day ago things went crazy . I started feeling very weak and my temp went up to +40 which almost killed me. In fact I passed way on the parking lot as i went to see my doctor . Since the I am like a ZOMBY ! After calling the doctor in the hospital he ordered stopping the drug right way Till my next visit with him on the 28-th of this month . He said that I have had allergic reaction from the drugs . Now he said that I may have to have my testicals removed and stop taking the drugs . By removing the testies that will stop the production of PSA !Good luck to you anyway .
Very sorry about your brush with sudden death. Lowering T either chemically or by ochiectomy will lower your T, but it will lower your PSA only until the PCa mutates to a type that needs very little or none human produced T. perhaps only one of those drugs is the culprit. I think you should talk to someone(your Doc at the hospital) ...an MO who specializes in PCa drugs, to receive better guidance on your best way to proceed!!!
Does your PCa produce much PSMA? If it does, have you looked into Pluvicto? My PSA went from 74 to 280 within a few months last year after a failed immunotherapy treatment. One actinium and 2 Lu-177 treatments had PSA down to .09. I know it doesn't work for everyone, but might be worth considering.
I think that is incorrect . Orgovyx blocks production, not reception. It is a production inhibitor (ADT) rather than a receptor inhibitor ( ARI). It is a second generation replacement for Lupron.
"Orgovyx ... works by blocking the pituitary gland from making hormones... thereby reducing the amount of testosterone the testicles are able to make. fda.gov/news-events/press-a...
it is a GnRH antagonist. It was developed as an alternative to the traditional GnRH agonists like Lupron and Eligard. It's the pill form of Firmagon. I've been on it 4 years. No psa flash and faster T recovery when discontinued.
The challenge, both study wide and anecdotal report wise is Xtandi and Orgovyx are relatively newer drugs. But as demonstrated by the EMBARK trial and other recent trials, Xtandi, even used alone, is superior when used in combination of radiotherapy to the older ADT drugs like Lupron (and probably Orgovyx since the mechanism of action it to reduce T it's just a newer drug than Lupron)
Correct me if I'm wrong, but I'm assuming most (not all) patients here first go on a T lowering drug like Lupron then when their PSA begins to climb again on that drug they switch to Xtandi? I think there is still research to be done not just on a one to one comparison as a monotherapy but on which sequencing of which particular drugs provides the longest delay to castration resistance and longest delay to metastases when it comes to these newer drugs. What appears to be clear though is that Xtandi is a superior form of ADT (used in the broad sense) to the older drugs like Lupron when trying to radiosensitive the cancer cells. However I doubt there is anyone here that used it during primary or salvage RT outside of a clinical trial ? I'm also assuming insurance wouldn't cover it in that context. But if so, an appeal citing the EMBARK and other trials may get approval for adding Xtandi during primary/salvage RT at an early stage of the disease prior to castration resistance and/or metastases.
AI is turning into such a great tool. The lastest Claude 3 by Anthropic based on many comparisons currently is giving me the most complete answers to my prompts:
Androgen Deprivation Therapy (ADT) is a common treatment approach for prostate cancer, which involves reducing the levels or blocking the effects of male hormones (androgens) in the body. Several drugs have been approved by the U.S. Food and Drug Administration (FDA) for ADT in the treatment of prostate cancer. Here's a list of some commonly used drugs for ADT and their approximate FDA approval dates:
These drugs initially cause a temporary surge in testosterone levels, followed by a sustained decrease in testosterone production by the testicles.
Androgen Receptor Inhibitors/Blockers:
Degarelix
Abiraterone acetate
Enzalutamide
These drugs work by either blocking the androgen receptor (degarelix and enzalutamide) or inhibiting the production of androgens (abiraterone acetate).
A google search on the approval history on Xtandi shows as of November 2023 it has approval for use in a wider setting of PCa patients! Hurray! (I'm guessing this may have already been discussed here but I'll include the info anyway for easy reference.)
"Xtandi ® (enzalutamide), following FDA expedited development and review programs (Priority Review designation, Fast Track designation, Real-time Oncology Review), based on results from the Phase 3 EMBARK trial. With this approval, Xtandi becomes the first and only androgen receptor signaling inhibitor approved by the FDA for the treatment of patients with nonmetastatic castration-sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR)."
Development timeline for Xtandi
Date Article
Jan 26, 2024 Nanoform Announces Important Milestone with Promising Clinical Results for Patient-Centric Nanotechnology-Enhanced Enzalutamide
Nov 16, 2023 Approval Pfizer and Astellas' Xtandi Approved by U.S. FDA in Earlier Prostate Cancer Treatment Setting
Jun 20, 2023 Approval Pfizer’s Talzenna (talazoparib) in Combination with Xtandi (enzalutamide) Receives U.S. FDA Approval for HRR Gene-Mutated Metastatic Castration-Resistant Prostate Cancer
Mar 17, 2023 Phase 3 Study Shows XTANDI plus Leuprolide Significantly Improves Metastasis-Free Survival in Men with Non-Metastatic Prostate Cancer
Oct 18, 2022 Lack of global regulatory coordination for cancer clinical trials costs 1.5 million lives a year despite therapies being available
Dec 16, 2019 Approval FDA Approves Xtandi (enzalutamide) for the Treatment of Metastatic Castration-Sensitive Prostate Cancer (mCSPC)
Jul 13, 2018 Approval FDA Approves Xtandi (enzalutamide) for the Treatment of Men with Non-Metastatic Castration-Resistant Prostate Cancer (CRPC)
Aug 31, 2012 Approval FDA Approves Xtandi for Late-Stage Castration-Resistant Prostate Cancer
I forgot to add it appears, study wise, the side effect profiles of Xtandi versus something like Lupron don't have stark differences. Xtandi appears to have a bit lower frequency of hot flashes but not fatigue compared to most of the others.
I had Claude elaborate on the side effect profiles:
Here are the top 4 side effects and their approximate percentages for each of the drugs listed for Androgen Deprivation Therapy (ADT) in prostate cancer:
Leuprolide (Lupron):
Hot flashes (55-58%)
Impotence (43-55%)
Fatigue (31-47%)
Muscle weakness (28%)
Goserelin (Zoladex):
Hot flashes (71%)
Impotence (44%)
Fatigue (38%)
Sweating (28%)
Triptorelin (Trelstar):
Hot flashes (53-59%)
Impotence (13-52%)
Fatigue (31%)
Nausea (9%)
Histrelin (Vantas):
Hot flashes (80%)
Impotence (64%)
Fatigue (22%)
Headache (11%)
Degarelix (Firmagon):
Injection site reactions (20-28%)
Hot flashes (26%)
Fatigue (25%)
Diarrhea (9%)
Abiraterone acetate (Zytiga):
Fatigue (39%)
Back pain (28%)
Arthralgia (27%)
Hot flush (22%)
Enzalutamide (Xtandi):
Fatigue (51%)
Back pain (26%)
Hot flush (20%)
Diarrhea (18%)
Relugolix (Orgovyx):
Hot flashes (54.3%)
Fatigue/asthenia (51.1%)
Diarrhea (12.2%)
Dizziness (6.9%)
Please note that these percentages are approximate and can vary based on different clinical studies and individual patient factors. Additionally, the list includes the top 4 side effects for each drug, but there may be other potential side effects associated with these medications.
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RT/RP vs RT/ADT OCSS (overall cancer-specific survival)
Statin use in advanced PCA with ADT or abiraterone/enzalutamide
Erleada vs Xtandi - what are the differences? 
Enzalutamide/Xtandi monotherapy as ADT with fewer side effects than Lupron
