This may be a stupid question but it's been on my mind for a while. I started on Prostap (Lupron) last July and my testosterone dropped to less than 1.0 by October while on just that. My PSA was also below 1.0 by then.
My MO started me on Xtandi towards the end of October and my T and PSA appear to have pretty much flatlined since then.
I've read that "castrate" level T is defined as <20 so if mine is <1, how much additional help is Xtandi likely to be giving? Could it just be driving my cancer towards castration resistance and more aggressiveness quicker than necessary?
Any thoughts are welcome.
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Benkaymel
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It's been pointed out in the APC forum that the units used in the UK (nmol/L) are different to the US (ng/dL) with a conversion ratio of about 29. So my T is actually hovering around 30 ng/dL which changes things somewhat! The Xtandi probably is helping more than I thought.
My SEs with Xtandi are generally not bad. I get regular hot flushes a bit more severely than on ADT alone but tolerable. I did have one bout of vertigo but have been fine on the full 160mg dose since then. No other obvious SEs at present.
Due to NHS restrictions, cycling Xtandi with Casodex is not an option. I have a one-time decision to make within 4 months of starting Xtandi (which will be next month) to switch to Zytiga but after that, I cannot change back. An interesting point you make that the cancer can mutate the ARs and use other food sources such as Xtandi - does that also potentially apply to Zytiga?
As a potential "fly in the ointment" to most, if not all, castrate-level PSA lab results, this response paper about the methodology used for low-level PSAs is worth noting.
Since they obviously make money on the multiples, it does seem they must not want to highlight the disparities between the methodologies. For high T's it would seem to not be all that significant, but for gauging ADT effectiveness, as with sub 0.1 PSAs, more accurate testing would always seem to be better. Thanks for providing a personal peek behind the curtain of the medical lab industry.
BTW, any idea about the import of free vs total T at low levels? Is testing even available or provided for free T at low levels? And if so, would it have any treatment value? (I'm aware of the 2% target for free with "normal" range T, so would that also hold true for sub 20 T?)
The test results reported are to 2 decimal places (see my Bio) - last one was 1.04 nmol/L and the lowest was 0.88 in October just before I started on Xtandi.
Xandi enzalutamide always seems to work from info I've seen.I was on it for just over 2 weeks.(I was given choice of chemo or xiandi)
From my research or delving, seems like you get a 5 month extension until castriant resistance from enzalutamide over what you would get with out it.
So if castriant resistance would have been in 2 years time,
You take enzalutamide for 2y and 5m and there's the 5 month benifit.....
So the 'is it worth it' to drive down PSA, then it works.
My thoughts where ' what's the pay of for the side effects' .......
Think I read xiandi may get dropped going forward(but cand remember exactly what the article was so it's just my gossip and not factual)
But I read your bio, says you did applutimide trial???
What happened on that? It's basically same type of second line hormone therapy that mops up the additional testestorone from different part of body.....
How come you on xiandi enzalutamide and not the eralda applutimide????
I think there is quite a bit of variation in the benefit from taking Xtandi from a few months up to several years extension for some people from the posts I've seen on here so like everything else to do with PCa, it's a bit of a lottery.
I've not heard that Xtandi is being dropped but you may be right. My SEs on it have generally been on the light side compared to many.
I'm not sure if you're replying directly to me because I've not been on any trials. I applied for Amplitude which would have included Zytiga but didn't qualify. I was put on Xtandi as that is the current SOC in the UK for de novo mHSPC.
Xtandi would increase T levels if not simultaneously using an LHRH ADT. It blocks AR in hypothalamus leading to perception of deficit and increased LH and testicular testosterone. So enzalutamide or apalutamide used without ADT will increase circulating T while simultaneously blocking it at the AR receptors. This may not apply to darolutamide which does not cross into the brain to reach the hypothalamus.
Bicalutamide as well as enzalutamide can control the cancer for some time (even years) without ADT for many. It did for me for 4+ years. However, one of the mechanisms of resistance is antagonist-to-agonist switching and it feeds the cancer and must be discontinued. This comes from point mutations in AR genes.
Other mechanisms for the eventual development of resistance to ARSI/AART drugs include AR amplification, AR clonal expansion, AR splice variants, and AR bypass to using glucocorticoid receptor GR to stimulate growth. Also increase rate of NEPC progression.
On the plus side: AARTs block the ARs, prevent their nuclear translocation, enhances T-cell immune mediated killing (CT2), down regulate NAIP apoptosis inhibitor and blocks AR mediated transcription. Because they effectively slow PC replication, this then slows the rate of mutations accumulation and slows progression to castrate resistance. Even though this will eventually fail if continued without interruption for long enough. (Why some of us are betting on BAT.)
The ARAMIS trial in nmCRPC showed increased metastasis free survival of 40.4 vs 18.4 months. And PSA progression (resistance) was 33 months vs 7.3 months.
Darolutamide appears to be the best of the AART in that: It is not as susceptible to the Point mutations causing antagonist-to-agonist switching as enzalutamide or apalutamide, is the most potent AR inhibitor and shows increased anti-tumor activity. Also does not cross the blood-brain barrier so has better side effect profile.
So in answer to your original question: if you are going to be on continuous ADT, then it appears to be of benefit to be also on an AART drug, or abiraterone.
I will also post this summary for my friends on FPC. Paul/MB
Paul, would it be better to try/start BAT prior to starting on Nubeqa, or can you start the Nubeqa first and then start the BAT months, on down the road. I'm having trouble getting a doc to submit Provenge for approval, so I have to get started on something. My PSA was up to 1.16 last week. My psa was .64 in November when I did the PSMA-PET scan, which only showed a small shadow of suspected cancer...thus unactionable with radiation, in its location, and probably not enough metastasis evidence to get insurance company to pay for provenge.
Either sequence is reasonable. It can be challenging to get an MO onboard with BAT. But that continues to improve with time. Some are speaking email or virtual consults with Denmeade. But you will need to declare yourself mCRPC and asymptomatic for him to green light it. Starting Nubequa first is fine as it gives you time under control. And even when it fails BAT can restore responsiveness. We are in the wild Wild West!
Makes sense Paul, thanks. I was well prepared in combat zones during my career, fighting in deserts but the wild west of cancer treatments, one might compare me to one of the guys from City Slickers, trying to succeed without any formal training.
Has anything positive come out of the guys trying 2nd line ARs without adt? or using 2nd line ARs intermittently, just like adt (during castration sensitivity)?
I suspect it is more like desert warfare. Fire but then move. Don’t keep fighting the same position or strategy. Keep changing it up. I use short burst of darolutamide integrated into my BAT cycles for example. All of the standard treatment regimens, if continued without interruption, will ultimately fail. That is always in the back of my mind. Fight from a position with a strong weapon for some time. Then move! It is called adaptive therapy.
Good comparison Paul. I agree, and that's been my gut instinct for a few years, but most of the MOs like to dig into trenchlines like WW1, and wait until they are forced to withdraw and fight from another location, if they are still alive. Speaking of adaptive theory, what happened with Nalakrats? It's appears that he totally left this site.
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