Thoughts? Testing the Addition of the Drug Relugolix to the Usual Radiation Therapy for Advanced-Stage Prostate Cancer (NRG PROMETHEAN)

[PCaWarrior]

clinicaltrials.gov/study/NC...

If I sign up for this, I would still be able to test my T levels. That would tell me if I was in the placebo arm or not. And I could also drop out at any time. And then you can give the team updates if you desire.

[petabyte]

If you are going to have SBRT anyway, then there is nothing to lose and potentially a more effective treatment to gain. I guess insurance would not cover the Orgovyx outside the trial?

Personally I'd do it if I fulfilled the criteria.

[PCaWarrior in reply to petabyte]

I like the auto scheduled PSMA PET scans and the orgovyx supply. I get orgovyx but sometimes have to pay a little (or beg my MO for samples).

They also provide CBC, CMP, lipids, etc. And some unusual genetic marker tests. And of course MO visits included. I pay a $100 copay today.

Thanks for the input!

[Seasid]

I really wonder why these people are not already on some ADT drug if you consider that the inclusion criteria request at least one metastasis up to 5 outside of the pelvis? If I were them I would probably request in addition to ADT probably also Abiraterone.

The only reason to enter into this trial is to get the SBRT radiation of the Mets and stay without the ADT drug (to have a testosterone).

I would probably try to avoid radiation by adding Abiraterone to the ADT and only later radiate my Mets if they are visible on the pet scan despite ADT plus abiraterone.

Radiation is a local treatment and it will not keep the cancer under control for a long time without a system treatment.

[PCaWarrior in reply to Seasid]

It would save me some money and some time. I have used abi and my MO thinks I can use a break from it. Looking at these studies I decided a year ago to follow MDT (SBRT) if warranted. I talked many times with the current head of ASTRO. He had a very positive opinion. He thought that I would have zero or limited side effects and if I zapped mets out every few years I would live indefinitely without ever having to pursue chemo, etc. My MO is also high on this approach.

ADT is not an exclusion. Your T needs to be >100 ng/dl at the start of the study. Very low but not castrate. You should be able to go off Zytiga 5 weeks prior and get there, or if you are using Orgovyx, 4 weeks. I have used Orgovyx, Lupron (separately), ARSIs, and AA. They are not curative in most advanced cases.

1. ASTRO 2022: Addition of Metastasis-Directed Therapy to Intermittent Hormone Therapy for Oligometastatic Prostate Cancer (EXTEND): urotoday.com/conference-hig...

2. Addition of Metastasis-Directed Therapy to Intermittent Hormone Therapy for Oligometastatic Prostate Cancer: The EXTEND Phase 2 Randomized Clinical Trial

pubmed.ncbi.nlm.nih.gov/370...

3. WOLVERINE findings highlight benefits of MDT in oligometastatic prostate cancer

urologytimes.com/view/wolve...

4. Metastases-directed therapy in addition to standard systemic therapy in oligometastatic castration resistant prostate cancer: A randomized phase II trial (GROUQ-PCS

ascopubs.org/doi/10.1200/JC...

5. ADT with SBRT versus SBRT alone for hormone-sensitive oligorecurrent prostate cancer (RADIOSA): a randomised, open-label, phase 2 clinical trial - ScienceDirect

sciencedirect.com/science/a...

However, I just noticed an exclusion that will apply to me:

"Prior radiotherapy to a lesion (i.e. oligometastatic recurrence by PET)"

[Seasid]

I agree that it is worth to try if it is possible to safely radiate a metastasis than why not, but when you say indefinitely it scares me.

My first oncologist was professor Richard Epstein and he was a Dana Farber oncologist at some point and he said to me to avoid local treatments and to focus on system treatments.

Ok, back then maybe they didn't have high precision MRI Linac Elekta Unity Swedish machine 500 M from where I am living now.

I am actually de Novo polymetastatic and don't have any illusion that I could stop ADT.

Maybe if someone has only one metastasis it could be worth to try if your partner bullied you into stopping ADT. Otherwise if you stick to ADT you could probably live comfortably 8 more years if you are not de Novo metastatic, but not me because I am de Novo polymetastatic and I have a metastasis even in my neck and spine and I have blood marrow involvement etc. plus I can decide for myself and I feel fine on ADT.

I did radiate my prostate and I do have side effects like fecal urgency etc.

Everything depends where your Mets are and how safe is it to radiate them. I may end up with radiating some of my visible metastasis if it is safe to do but at the moment I hope that I don't have any visible metastasis because my Mets are under control with ADT alone and I added Bicalutamide one year after my prostate radiation.

Plus I am not eligible because I had early docetaxel chemotherapy because if you are de Novo metastatic than it is a right thing to do.

[PCaWarrior in reply to Seasid]

Thanks for the input. I'm 7 years in and doing well today. But what will tomorrow bring?

I'm paraphrasing what the RO said but he did talk about some of his patients and how well they were doing. He seemed very intelligent. We had some good conversations.

At some point my life expectancy "takes over". So for me indefinitely can't mean more than 20 years.

[Seasid]

Could you please fill out your profile? It would help to understand better your situation.

[PCaWarrior in reply to Seasid]

Sure

[petabyte in reply to PCaWarrior]

Wow, that's an interesting journey!

I was wondering, did you get any prophylaxis for gynocomastia when on E2 ADT? I'm considering adding low dose E2 patches but will probably try s-equol before. Will get a DEXA scan soon to see if high dose vitamin D is helping sufficiently: acsjournals.onlinelibrary.w...

I really need to update my bio, yours has inspired me!

[PCaWarrior in reply to petabyte]

Thanks. When I was using tE2 I used it first for ADT. The dose was 0.3-0.4 mg/day. Took my E2 to hundreds of pg/ml. After a few months I started getting gyno.

Lately I've used it for E2 replacement. Low dose. 0.05 mg/day approx. No gyno.

Thanks for the link. I don't know if it was during the tE2 ADT treatment or the dutasteride/casodex treatment or the high androgen treatment but something made my bone mass increase substantially. High E and high T can both do that.

I'm due for another scan.

[petabyte in reply to PCaWarrior]

BTW they are recruiting for a phase 3 study.

clinicaltrials.gov/study/NC...

but level 2 evidence is fine by me when there is not a lot of downside. My serum minerals are measured regularly on Abiraterone and I get vitamin d measured myself (at a lab)

[PCaWarrior in reply to petabyte]

Thank you! I haven't seen that one. Looks very promising.

I agree, I don't always wait for phase III clinical trials before doing something.

Not much downside to D3. Although 60 ng/ml might increase mortality risk. Less than 30 ng/ml also appears bad.

[petabyte in reply to PCaWarrior]

Thanks for that, it reminded me I needed to check out risks of high vitamin d levels.    Seasid already pointed out the risk in a private chat a few days ago and I was meaning to chase it down.

With 2000 IU per day I had 32 μg/L (80 nmol/L) With 10000 I had 46μg/L (115 nmol/L) On Friday it was 92 μg/L (230 nmol/L) but I have changed how I take it. Now it is with the evening meal. It's in the reference range 30-100 here but still too high.

(Each of those measurements were taken with a stable intake over a few months.)

Perplexity with deep research: perplexity.ai/search/my-lat...

The evidence on the high side is not compelling but I will reduce the dose to reduce the potential risk (none next week then 40000 after that).

[PCaWarrior in reply to petabyte]

I thought there was a decent amount of evidence. Why do you suggest it's faulty?

Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses - The Lancet Diabetes & Endocrinology

thelancet.com/journals/land...

You can find lots of studies like this. Most of the ones I've seen that do not show a bathtub curve simply do not go up high enough.

When I first started I took 75kIU/week. My D went up but not quite as high as yours. The sweet spot for me is around 3-6 kIU/day. Depending on the K2 you take and your metabolism, sun exposure, weight, etc. you might need more or less.

"I target 75-130 nmol/l serum levels (30 – 52 ng/ml). This can be easily achieved by vitamin D supplementation. As of 10/2018 my serum levels were 26 nmol/l and as of 8/26/2019 they were 181 nmol/l. Note that it took me less than 3 months to increase my vitamin D level. I was taking up to 75kIU of vitamin D each week and getting perhaps 60 minutes of direct sunlight a week (sunlight also increases serum vitamin D). I made a mistake and overshot my target so now I take a dose of 5kIU a day and adjust as necessary to keep my serum D in the target zone.

This is a nice vitamin D calculator grassrootshealth.net/projec...

The optimum form of vitamin D for supplementation is D3. It is also necessary to take some vitamin K along with the vitamin D (K2 with a mix of MK4 and MK7 forms is preferable).

"

[petabyte]

I didn't look at that study but it does seem well designed from my limited experience although they seem to be more focused on the low end. The graphs are interesting but suspiciously smooth and extrapolation to higher values may not be valid.

My CVE risk is low: confirmed with cardio CT Angiogram, EKG and Echocardiogram when I started Abiraterone. I'm also in pretty good shape.

So while there may be some relative risk, the absolute risk is an acceptable trade-off for me (for a short time). But I think low dose E2 may be the way to go anyway.

It's a pity they didn't report the D serum levels in the ADT study (or maybe they did in the full text which isn't even on sci-hub) . The intake is probably less relevant.

I take D3 with K2 (Mk4 and 7).

I will reduce intake with the improving weather as well 😎🌞🌻

Vitamin D risk

[PCaWarrior in reply to petabyte]

Good! Many guys miss out on the MK-4. More research on MK-7. I don't know if there is a simple way to define the quinones. I should look into it.

Yeah, the curves are smooth but they have like 3000 or so data points. And they might have extrapolated some. Most studies are at least an order of magnitude smaller.