I have been on Nubeqa as a mono-therapy now for just over 3 weeks, and the first blood draw was very encouraging. After being on a nice drug holiday for the past year, PSA was starting to rise again with a doubling rate of 4-5 weeks. PSA was at 5.0 when I started the nubeqa, and as of Tuesday it was down to 1.6 . The only side effects have been a little mild fatigue (nothing compared to Firmagon with Xtandi), and some breast pain and development. I will probably try some low dose Tamoxifen before things get out of hand, and Im sporting a D cup rack. I am so far very pleased with Nubeqa, and hoping for continued PSA decline, and a nice, long run on it ! I think it may be the best new anti-androgen out there.
Nubeqa (Darolutimide) mono-therapy up... - Advanced Prostate...
Advanced Prostate Cancer
I am SO glad it is working for you! After one month on darolutamide, I wanted to eat a gun. My understanding is that this must be administered in conjunction with Lupron/Eligard? I
I had way too many bad side effects from Eligard and Firmagon, so I am no longer taking them. I have been castrate resistant for the last 2 years and so they do very little to slow the cancer anyway. The "Standard of Care" dictates that Nubeqa be taken with one of the castration drugs like Eligard, but i have become annoyed enough with their stupid SOC that I am no longer going along with it. It also dictates that Darolutimide only be used for non- metastatic castrate resistant cancer, and I am metastatic. So far so good. So you had a bad experience with Darolutimide?
Joeguy, SO glad to hear you are getting positive results! Good for you for pushing for what you feel you need in the way of treatment.
Keep it up and keep the faith ✌️
definitely keep us all informed on how this goes. my guy is either "cured" or on a vacation, and nubeqa is of interest if his PSA starts to rise again. lupron plus zytiga turned out to create horrible side effects from each drug separately, so he'd be looking for the next option.
Great to have your report. I guess testosterone levels are very high because it accumulates with nowhere to go. Do you take finasteride to prevent conversion to DHT?
My T is normally low at around 200..... as of Tuesday it is 450. I am experiencing some breast pain and growth, but not bad. I am not familiar with finasteride, but I am considering low dose tamoxifen based on recommendations from you and others. Does the conversion to DHT happen before the conversion to estrogen?
There are 2 metabolic pathways for excess testosterone - it gets converted into estrogen or DHT. Both occur at the same time. Finasteride will block conversion to DHT. DHT is a very powerful androgen. Maybe Darolutamide blocks it too, but I don't know that for a fact. It seems an easy enough precaution. Tamoxifen will block estrogen in breast tissue. You don't want to take an aromatase inhibitor (e.g., Arimidex) to prevent estrogen entirely because the estrogen has some other good effects (mood, bone health, hot flashes, etc.).
Not that I necessarily trust Wiki, but this is what they say.....Darolutamide is a second- or third-generation nonsteroidal antiandrogen (NSAA). It acts as a selective competitive silent antagonist of the androgen receptor (AR), the biological target of androgens like testosterone and dihydrotestosterone (DHT). Its affinity (K i) for the AR is 11 nM and its functional inhibition (IC 50) of the AR is 26 nM.
That's from mice. The problem for you is that so far it has only been tested in humans who are also taking a GnRH agonist. So it may effectively block T and DHT when they are both at very low levels. But what about when both T and DHT are elevated? There are no clinical data. Your low PSA is certainly a good sign. But whether or not it would remain low longer with a combination is TBD. (it can take several years for the advantage to become apparent)
With the lesser antiandrogen, Casodex, we know the monotherapy is inferior to just a GnRH agonist alone.
But Xtandi wasn't inferior, at least in the short-term:
(Zytiga monotherapy seems to be successful too, but unlike anti-androgens, it lowers testosterone production)
Whether Nubeqa+ADT is better than Nubeqa can only be decided by an RCT like this one:
Tall Allen may I ask you a question? Do you live in America and if so are all the drugs abt all called different names then here in England,? I here so many men talking about so many meds that I haven’t heard of, I’m trying my very best to become knowledgeable well a little anyway on this disease for my par and know were to go next I would be so grateful if you could answer my questions thank you and I hope your well x
Which drugs are you referring too? Some on this for use the name brand/generic name interchangeable so it could appear there are more drugs when in fact its the same handful.
I think this covers all the currently approved drugs in the US. Here are the brand names and the generic names.
Xofigo= radium 223 dichloride
Lupron, Eligard = leuprolide
Zometa = zoledronic acid
Yes that’s it then, thank you so much if your psa rises with your standard adt therapy eg my pa is on prostap dcs injections every three months could your mo change it to something else but still along side xtandi? Thank you so much for your responding x
Where did you end up going for treatment?
I am still at Urologic Specialists, and OCSRI in Tulsa
Guessing OCSRI is more involved with your treatment at this point, is that right? Just asking in case I need a MO any time soon.
Oddly enough, my Uro (Dr Doyle) seems to be much more knowledgeable about prostate cancer treatment than my MO at OCSRI (Dr Cole). So I actually rely on the advanced prostate cancer clinic at Urologic Specialists more.
Good to know. Didn’t know they had an Advanced Clinic. I used Dr Goad for RO, affiliated with their group.
well thats what they call it anyway...... not sure how much of a "clinic" it really is since its mostly all urologists. They actually are pretty helpful though. For example, they have nurses that help with getting the super expensive drugs like Xtandi and Nubeqa for very little, to no cost.
Very bold experiment in Nubequa mono therapy. Encouraging start. Watch it carefully and keep us informed.
Do you know what your estradiol [E2] level is? It needs to be above 12 pg/mL (imo) but less than 30 PG/mL. I would opt for Arimidex to control higher levels. Arimidex is an aromatase inhibitor, so it inhibits the conversion of T to E2. The enzyme aromatase tends to be elevated in PCa cells. Normal prostatic epithelial cells have no need for E2. I think that there is a case for Arimidex anyway, as long as E2 does not dip below 12 pg/mL. [You wouldn't need Tamoxifen imo.]
Do you know your DHT level? If DHT is elevated, I would use Dutasteride rather than Finasteride. Finasteride only targets type II 5AR, whereas Dutasteride targets types I & II.
Note though, that serum DHT might be low, but PCa cells might have upregulated 5-alpha reductase, so some of us use Dutasteride anyway to block that escape pathway.
Testosterone is not fated to become E2 or DHT. In men with normal T, >650 ng/dL say, E2 is not generally a problem, and DHT doesn't go wildly out of control. If you want to read about T metabolites, see below.
"Both testosterone and 5α-DHT are metabolized mainly in the liver. Approximately 50% of testosterone is metabolized via conjugation into testosterone glucuronide and to a lesser extent testosterone sulfate by glucuronosyltransferases and sulfotransferases, respectively. An additional 40% of testosterone is metabolized in equal proportions into the 17-ketosteroids androsterone and etiocholanolone via the combined actions of 5α- and 5β-reductases, 3α-hydroxysteroid dehydrogenase, and 17β-HSD, in that order. Androsterone and etiocholanolone are then glucuronidated and to a lesser extent sulfated similarly to testosterone. The conjugates of testosterone and its hepatic metabolites are released from the liver into circulation and excreted in the urine and bile. Only a small fraction (2%) of testosterone is excreted unchanged in the urine.
In the hepatic 17-ketosteroid pathway of testosterone metabolism, testosterone is converted in the liver by 5α-reductase and 5β-reductase into 5α-DHT and the inactive 5β-DHT, respectively. Then, 5α-DHT and 5β-DHT are converted by 3α-HSD into 3α-androstanediol and 3α-etiocholanediol, respectively. Subsequently, 3α-androstanediol and 3α-etiocholanediol are converted by 17β-HSD into androsterone and etiocholanolone, which is followed by their conjugation and excretion. 3β-Androstanediol and 3β-etiocholanediol can also be formed in this pathway when 5α-DHT and 5β-DHT are acted upon by 3β-HSD instead of 3α-HSD, respectively, and they can then be transformed into epiandrosterone and epietiocholanolone, respectively. A small portion of approximately 3% of testosterone is reversibly converted in the liver into androstenedione by 17β-HSD.
In addition to conjugation and the 17-ketosteroid pathway, testosterone can also be hydroxylated and oxidized in the liver by cytochrome P450 enzymes, including CYP3A4, CYP3A5, CYP2C9, CYP2C19, and CYP2D6. 6β-Hydroxylation and to a lesser extent 16β-hydroxylation are the major transformations. The 6β-hydroxylation of testosterone is catalyzed mainly by CYP3A4 and to a lesser extent CYP3A5 and is responsible for 75 to 80% of cytochrome P450-mediated testosterone metabolism. In addition to 6β- and 16β-hydroxytestosterone, 1β-, 2α/β-, 11β-, and 15β-hydroxytestosterone are also formed as minor metabolites. Certain cytochrome P450 enzymes such as CYP2C9 and CYP2C19 can also oxidize testosterone at the C17 position to form androstenedione.
Two of the immediate metabolites of testosterone, 5α-DHT and estradiol, are biologically important and can be formed both in the liver and in extrahepatic tissues. Approximately 5 to 7% of testosterone is converted by 5α-reductase into 5α-DHT, with circulating levels of 5α-DHT about 10% of those of testosterone, and approximately 0.3% of testosterone is converted into estradiol by aromatase. 5α-Reductase is highly expressed in the male reproductive organs (including the prostate gland, seminal vesicles, and epididymides), skin, hair follicles, and brain and aromatase is highly expressed in adipose tissue, bone, and the brain. As much as 90% of testosterone is converted into 5α-DHT in so-called androgenic tissues with high 5α-reductase expression, and due to the several-fold greater potency of 5α-DHT as an AR agonist relative to testosterone, it has been estimated that the effects of testosterone are potentiated 2- to 3-fold in such tissues."
Happy for you buddy! Keep beating it down!
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