which is better to suppress PCa…Rad-140 or R1881?

[Farmhand]

jci.org/articles/view/146777

Article discussing SARMS and PCa

[Farmhand]

Thanks for the informative explanation, so you don’t use Rad-140 to suppress PCa, only to improve muscle mass, bone density, energy level during low T…. are you reducing SARM dose because of effect on PCa?

[Scout4answers]

I would exercise caution when using RAD140. My experience seems to indicate that use of SARMs may have caused my PSA to rise. I will know more in a week or so when I get re-tested for PSA. See my profile for more details.

[KocoPr in reply to Scout4answers]

if you could control your psa with intermittent SARMS and continuous adt/ARi you could keep your cancer androgen sensitive, we hope!

[KocoPr]

Here’s a thought. Kind of like BAT is keeping the PCa using androgen receptors instead of becoming drug resistant thus keeping the cancer at a consistent low level.

Of course you need to continue adt and an ARi. Just something to think about.

Preventing castrate resistance is the best case scenario at this stage since there is no cure, YET.

[KocoPr in reply to KocoPr]

So if PSA starts to climb, maybe stop the SARM and let the ADT and ARi do it’s job till PSA drops back down and cycle it like that. For me on Osterine which has no affinity to aromatase nor 5a-reductase and darolutamide has a stronger binding to the AR than enzy, and Apalutamide.

[Farmhand]

ok, thanks…..that makes sense. Why not Xanti? I’ve only used abiraterone so far… But was considering off and on enzalutamide for a modified BAT program in the future. If you are not using enzalutamide in your modified BAT program, what are you using to replace it? And What is the issue with Enzalutamide?

[Scout4answers]

The first rise was missed because of other moving pieces (Zytiga @ 250 moving back up to 1000 which I thought was the cause ) The second was clearly a correlation as It was done by itself without any other changes. Time will tell, if PSA goes back down and stays there I will know the rise was SARMs related.

[Farmhand]

Have you written a book about your experiences with BAT? ….interested!

[Farmhand]

is 150 mg Casodex needed, or would the standard 50mg do the trick when combined with Zytiga?

[KocoPr]

all good points but what i was contemplating was doing these low dose SARMS at the same time as SOC, then when your PSA starts to rise get pff the low dose SARMS until your psa falls back to your desired level.

[KocoPr]

im not going to convince my OC to do BAT. He is prescribing me daro off label and through a grant so im very grateful for that and don’t want to endanger that.

[Ramp7]

When I met with Denmeade, he stated that Lupron and Testosterone would work fine. I too am using Propionate. Just finished the High side of my second cycle. Responding well so far.

[MateoBeach]

For those who might have gotten a little confused from this (very informative) article, I will post their conclusions below. They have shown that strong AR activation ( not antagonism) correlates with PC growth suppression in most cell lines and xenografts tested, Whether by high dose testosterone or by SARM. So an oral SARM such as GPX-024 (enobosarm) or topically absorbed CPD-26 can potentially supplement or replace high dose testosterone in modified BAT regimens.

Alternating with some period of castrate T levels and or AR blockade may prevent PC adaptations such as progression to CRPC, AR mutations and such forms of treatment failure emerging. Additionally, periods of castrate levels or AR blockade permit AR amplifications which could further enhance the therapeutic effects of high testosterone or SARM cyclic deployment. MB

“The effects of bipolar AR activation were not evaluated in this study. Preventing adaptation to a static, low or high androgen environment may be crucial, for long-term suppression of tumor growth. Understanding changes in gene expression, physiology, and the epigenetics of cells exposed to a changing androgen environment may help improve therapy by identifying feedback mechanisms that can be further exploited. Additionally, the current 28-day treatment cycle of BAT may not be the most effective. Given the control afforded by the drug-like properties of SARMs, shorter or longer treatment intervals could be evaluated to optimize the bipolar AR for the greatest effect.Future studies into the use of nonsteroidal agonists to suppress the growth of PC should explore strategies that augment the activation of the AR. One avenue could be to evaluate nonsteroidal, full AR agonists. Safety concerns notwithstanding, full agonists may be more effective replacements for steroidal agonists by potently inducing AR signaling, regardless of the cellular context, and so could induce the same systemic effects as those seen with T. Other possibilities include cotherapeutic approaches to directly activate the N-terminal domain of the AR or stabilize AR levels (52–54).Our findings strongly support further exploration of SARMs for the treatment of CRPC. The nonsteroidal compounds SARM-2F, T8039, GTX-024, and Cpd26 potently induced AR activity, repressed MYC signaling, and suppressed the growth of PC cells. SARMs compared favorably to steroidal androgens by regulating a largely overlapping set of genes and recruiting the same set of AR cofactors to chromatin. Since SARMs have already been tested in a variety of clinical settings for other health conditions, the path to implementing them in the clinic as a CRPC therapy could be accelerated. Given their convenient mode of delivery, favorable safety profile, and potential to improve general health, SARMs present an attractive therapeutic option.”

[Scout4answers in reply to MateoBeach]

As a non scientist most of your post is above my pay grade. Any thoughts on why RAD 140 would potentially raise my PSA ?

[MateoBeach in reply to Scout4answers]

They found that RAD 140 failed to suppress PC in some cell cultures. So it is probably not the best choice for us. Better would be GPX-024 (enobosarm). And dose must be high enough, not low dose. But I cannot convert their nano and pico Molar concentrations in solution into meaningful dose estimation for humans. GPX-027 was used in a clinical trial for AR positive breast cancer. So perhaps the dosing used could be informative.

Two other SARMs, lgd-4033 and RAD-140, failed to suppress the growth of LNCaP cells (Supplemental Figure 1, A and B; supplemental material available online with this article;

doi.org/10.1172/JCI146777DS1), indicating that molecular differences in SARM structures influence cellular responses (Supplemental Figure 2, A–F).

[MateoBeach in reply to Scout4answers]

Here you go: Dose of 9mg/day of enobosarm (Osterine) in AR+/ER+ Breast cancer. ARTEST trial.\

The FDA has granted a fast track designation to enobosarm (Ostarine) for the treatment of patients with androgen receptor (AR)–positive, estrogen receptor (ER)–positive, HER2-negative metastatic breast cancer, according to a press release from developer Veru Inc.1The therapy was evaluated as part of the phase 3 ARTEST trial (NCT04869943), which evaluated the safety and efficacy of oral enobosarm at a dose of 9 mg daily in roughly 210 patients. Patients were in their third line of treatment for metastatic disease, and had progressed following treatment with a nonsteroidal aromatase inhibitor, fulvestrant, and a CDK4/6 inhibitor.

[MateoBeach in reply to MateoBeach]

cancernetwork.com/view/fda-...

Note that 18mg/day did not provide any additional benefit, and in fact did worse.

[Scout4answers]

thanks always informative and understandable to a finance guy.

What is the equivalent to ar+ and er+ breast cancer in terms of PCa ?

Do I understand correctly that it only slowed progression by 5.4 months at best?