I've heard they've been doing this in Germany recently. Is anyone familiar with Lu-177-PSMA-I&T for Metastatic Castration-Resistant ogliometastatic spine mets?
Compared to chemo?
Survival time increase?
Side effects?
Lu-177-PSMA-I&T for low volume Metast... - Advanced Prostate...
Lu-177-PSMA-I&T for low volume Metastatic Castration-Resistant Prostate Cancer
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SViking
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Lu-177-PSMA-I&T is available in a randomized (2:1) clinical trial in the US for men who are chemo naive.
clinicaltrials.gov/ct2/show...
These 2 may have less kidney toxicity:
clinicaltrials.gov/ct2/show...
clinicaltrials.gov/ct2/show...
That's good to know because I have an atrophying kidney. Why would one med be less problem for kidneys?
It is the ligand that determines how much time it hangs around in the kidneys.
I am being screened for a trial, Eclipse - A Multi-Center, Open-Label, Randomized Phase 3 Trial Comparing the Safety and Efficacy of 177Lu-PSMA-I&T versus Hormone Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer, at St. Louis University School of Medicine, next week. I have failed Apalutamide, after 6 months, with 2 new bone mets, & my MO feels it best for me to try this trial, instead of Chemo. As has been pointed out, in the US, I think one must normally fail Chemo before allowed to seek 177Lu per SOC's.
Lu-177-PSMA-I&T and Pluvicto are very similar. I&T is not more effective for low-volume mCRPC than Pluvicto.
I thought that Pluvicto was to toxic for low volume disease so they came out with this other one.
If there are just a few mets they can reduce the dose to e.g. 6 GBy. However, the side effects are low, so with a higher dose you may need fewer cycles.
GP24 is correct. Pluvicto (G68 ligand) and Lu-PSMA-I&T are small molecule ligands for lightly bonding the isotope on the cell surface of the cancer cells at the PSMA protein sites. However, their binding is weak and reversible and both are filtered out through the kidneys. So both have some degree of renal toxicity. Doctors and centers in Germany and Australia who are experienced with both consider them essentially equivalent, though they have not been formally tested head-to-head.
The only alternative ligands that are different are the large-molecule monoclonal antibody ligands such as Lu-PSMA-J591. It binds much more strongly to the cancer sites so is more efficient (less isotope needed for treatment). And it is not filtered through the kidneys so does not carry nearly as much kidney toxicity risk. Instead it is removed through the bile and eliminated via the intestines. Because it persists in the circulation longer, the main toxicity is temporary bone marrow suppression and blood cell cytopenias. I have had Lu-PSMA-J591 treatment for low volume residual disease ar GenesisCare in Perth with excellent results so far 9 months after one round of two treatments.
Are you satisfying the following inclusion criteria?:
"Progressive disease by one or more of the following criteria:
Serum/plasma PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week apart with a minimum start value of >2 ng/mL.
Progression of measurable disease (RECIST 1.1) or presence of at least two new bone lesions (PCWG3 criteria)."
Did you ask about PSMA therapy your MO? What did she,/he say about this idea?
She is onboard with it however not real knowledgeable on the subject.
What is your PSA now and how many (if any) visible Mets do you have now?
Is your PSA rising or stable?
What is your current treatment?
PSA .76 and rising. One small spine met and one small rib met as revealed on last PSMA test.
Why don't you just do SBRT as soon as possible?
I would suggest you consider SBRT to the two met sites. Then follow with the two infusions of Lu-PSMA-J591. You can consult with Dr. Nat Lenzo at Theranostics AU/GenesisCare. They may also be offering this in Sydney by now. Paul
I just wish to say that Eugen Quan from Mayo clinic is recommending Lutetium first and then SBRT to the Mets.
I believe the reason is because lutetium is system therapy therefore more beneficial than SBRT alone.
SViking problem is that he is low volume now and not really eligible for Lutetium treatment. (It may change).
Radiation adds up and the there is a possibility that the blood work drops preventing further radiation therapy.
I am not an RO therefore I don't really know, but all of these radiation therapies should be considered on a case bu case basis by a competent RO which is doing his job not just as a pioneering knowledge gathering exercise but because he believes what he is doing.
My RO didn't let me take Zytiga after the SBRT of my prostate saying that I should save up Zytiga for the future as we all know that all therapies fail at some point of time and the cancer always wins.
There are few people which are hanging around for a very long time. Others wanish in a few years mainly as a result of bad treatment decisions.
For example some take drug (ADT) holidays, some start BAT and there cancer progress quickly on high testosterone. Etc.
Taking part in a clinical trials also has their own risk. Usually trials evoluate (approve) for example Lutetium.
In such a clinic trials they will not give you parallel to lutetium for example Enzalutamide.
I know someone who had lutetium PSMA treatment and his PSA where going up. I asked him why they don't give him Enzalutamide and he said because they want to see the effectiveness of the Lutetium PSMA therapy.
We don't really know what is better, a sequential therapy or everything hit it hard in a same time treatment.
I was happy with the results of Nubeqa, ADT plus early chemotherapy.
50% of people survived 4 years on early chemo plus ADT while 63% survived 4 years on Nubeqa + ADT plus early chemotherapy.
I was thinking hard about these results and I believe that certain people would probably live even longer on early chemotherapy plus ADT. Therefore everything is a lottery and it would be beneficial for you if you have knowledgeable MO and ROs in a centre of excellence with a great team.
It would be very naive thinking that if you get BAT , Lutetium etc in a same time that it would extend your life.
I personally would try to get Provange immunotherapy as soon as possible. My MO doesn't believe that Provange is useful as it doesn't lower the PSA. I personally believe that it could be useful for me but I just don't have enough money to pay for it.
Well I agree with you on Provenge. Get it if you can! Unfortunately only approved here in USA if mCRPC. Real world results show over a year of added OS, even though PSA not indicative. I would not accept that thinking from my MO.
As for the timing of SBRT and Lu-PSMA, especially with the superior radioligand, J591. Australia is where they have the most experience with it and are currently doing clinical trials with it. Nat Lenzo in particular. Yet he says he is not yet sure if it is better with SBRT to oligomets first, followed one month later with the two treatments of Lu-J591 (as I had), or the opposite sequencing. He is doing both sequences based on practicalities of individual patients. You do not need to have any remaining PSMA avid lesions on scans for the J591 to work on micro mets and cancer stem cells. So the criteria for Pluvicto are not applicable. And of course I am not going to wait for further clinical trials before such treatments. Not letting my cancer have that long to further progress. My PSA is down 90% after SBRT / LuJ591 treatment sequence 9 months ago. So far so good.
The interesting thing is that my last PSMA Scan showed two small lesions, one spinal on my T3, and the other on the nearby rib. However, when the MO at UCLA ordered an MRI prior to making an appointment for SBRT, there was no indication on the report of new lesions. So, the MRI did not see what the PSMA Scans did? How strange is that?
I really don't understand the purpose of the MRI? Only if it is ordered to see your spinal cord?
I don’t understand the reason for an MRI in advance of treatment either. The first time I did proton treatments they did an MRI first also. Then on two subsequent SBRT treatments at UCLA they also required an MRI in advance. In fact at UCLA they are starting to do MRI guided SBRT. And so far none of those radiation treatments lowered my PSA even for a moment. And I was on ADT before, during and after treatments. The moment I went off ADT and my testosterone went up, so did my PSA.
I agree for 2 infusions of J591 I would also do in an oligometastatic setting the SBRT first.
I believe Eugen was talking about pluvicto 6 infusions.
My latest PSA 2 month after SBRT dropped from 1.4 to 0.38.
Do you have a link for the clinical trial with J591 in Australia? I will also consider it, but first I will see how low will my PSA go after the SBRT of my prostate.
If it stays low on Degarelix injection only I will not rush.
I am declared hormone sensitive again by professor Joshua at my last meeting with him a week ago.
I am on Degarelix injection for 4.5 years now and don't qualify for clinical trials in a hormone sensitive setting.
To enter the lutetium plus enzalutamide the maximum allowed time is 3 years on ADT.
If you are still hormone sensitive 3 years after starting ADT after your initial diagnosis you are excluded from entering into that clinical trial for HSPC.
Do you know any clinical trial for HSPC which would allow you to enter after 4.5 years on continuous ADT if you are still declared hormone sensitive like me now?
See my Bio but I had only 1 lesion, PSA 0.4, after off Lupron for 1.5 yrs. was designated Oli & had SBRT (Cyberknife) to it. Unfortunately my T continue to rise from 200's to 300's and the invisible mets. went crazy; too numerous to count. That is when I went back on Lupron & added Apalutamide. So, be careful about assuming SBRT will do it. We are all different.
Thanks, i probably could already get a free ADT after being 4.5 years continuosly on it, but I will definitely continue on Degarelix.
I never wanted to stop ADT or to start BAT with my polimetastatic status.
My first oncologist professor Epstein wanted to put me on intermittent ADT what I flatly rejected.
Stopping ADT, starting BAT are bad treatment decisions for a person who has a met in his neck under his skull.
I regret that I went off after 2.5 yrs. but my wife thought I getting too grumpy - "oh you mean like a grumpy ole man"? I was 72 at the time, so what do we expect, at that age? 😜Each person is different.
I am on Degarelix ADT only and I could be very nice if I want to be nice.
I will search the internet for "grumpy old man". 8 don't know what it is. Old people are usually nicer than young people.
I would not stop my treatment just for that. I feel perfectly fine. I just want to live to see my children.
Yeah, as the PCa came back that is when I went on the Apalutamide/Lupron but they only lasted 6 months. I still wonder if the fact that my T only got to 37 that it let it break through. Seems their is dispute over what the T value should be for castrate resistance, <50 or <20? My MO feels the former is enough.
Regardless, in this Eclipse trial, assuming I qualify, & I draw the short straw, I will start out with Zytiga & that will drop my T even more, I assume. And then if that fails, I get to try LU1177, which my MO feels is the better choice over Chemo, which would be next under SOC.
I hear you on your kids, I have 2 grandchildren & possibly more on the way & would like to see them grow up as much as possible!
I'm covered under Medicare for Provenge. I wonder if they would pay for a repeat treatment further down the road.
Has anyone here had any experience with Lu-177-PSMA-I&T?
Lu 177 PSMA I&T has been available for years.
I had treatment with this ligand in 2016 at the TUM in Munich where this ligand was developed..
One potential advantage of the I&T version is that the ligand is a smaller molecule than the ligand of Pluvicto.
This could make easier for the ligand with the Lu 177 to be internalized when the PSMA retracts from the surface of the cancer cells which could facilitate the Lu 177 getting closer to the DNA of the cell.
There is not evidence that Lu 177 PSMA I&T is more effective than Pluvicto.
One treatment destroyed all the mets (many lymph nodes in the pelvis and in the retroperitoneum)
We stopped ADT after the Lu 177 PSMA treatment but my testosterone never recovered. I continue on "free ADT" and mets reappeared 7 years later. Only lymph nodes mets. . None is a recurrence of the old mets.
Lu 177 PSMA is not a cure for metastatic prostate cancer, the same than chemo, or the new anti androgens, so is not surprising the cancer progressed. We are doing a new treatment with Lu 177 PSMA to control these new mets.
That's great news. Seven years with no ADT or progression. If I do the treatments I plan to add Provenge. Would that help? I would love to get off ADT at least for a few years.
You had excellent response, Tango, and a long run. But your recurrence is sobering. Are you going with I&T again, or would you consider J591?
I guess it would be in poor taste to comment that, I’m dying to know more about this.
As MateoBeach suggest a combination of some type of external beam radiation and radioligand therapy may be efficacious in low volume disease. Nat Lenzo told me that in 2018 and I subsequently went that route in Heidelberg Germany.
I had 3 soft-tissue mets in my left infraclavicular area that were psma positive. My psa had a rapid doubling time. I corresponded with the Heidelberg group and with Nat Lenzo in Australia. Was planning on going to Australia but travel was restricted so went to Germany. Based on tumor volume I received one cycle of a combination of LU177 and Ac225. The was dense uptake on the post treatment scan. I followed up as Lenzo suggested with fractionated radiation therapy here in the US. I am now 19 months out with my psa below 0.01, the limit of the test. I have had some dry mouth but it has improved and is something I can live with. Like everyone I live from lab test to lab test and have had followup choline pet and mri at Mayo which have been negative to date. Going to Germany was easier than getting a primary care appointment here and it was incredibly easy for me to upload all the scans to their site. I hope this helps.
Thank you so much. Are you still on some type of ADT? And if you are, do you think there’s a possibility of ever going off ADT?
Did you also consider Provenge?
Yes still on eligard and zytiga/decadron. I do not realistically see ever coming of ADT until the end. I believe Provenge to be a last ditch effort with little real scientific support. Maybe just my person bias but one as to wonder why no new significant information has really come forward on Provenge.
it’s my understanding that provenge only has a good effect early on and for low volume disease. What is stopping you from using Provenge now? I was told by my oncologist that because I am now castrate resistant that Medicare will pay for provenge, so what do we have to lose?
yes, available in most countries now, including UK and US where is it Pluvicto from Novartis
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