Anyone have experience with Ac-225 after Lu-177

[WhiteStrat]

I have had 3 cycles of Lu-177 and it has not helped. My PSA has gone from 40 to 80 in 4 months. Scans show disease progression in bone mets. My Med Onc says the progression is "slight" since June, 2020 but any progression seems bad to me. Anyone had Ac-225 treatment? If so, did it have any effect on bone mets? What were the side effects? My doctor in Munich, who would administer the Ac-225, is very concerned about the potential side effects, especially permanent damage to salivary glands.

[tango65]

This is a recent commentary about Ac 225 treatment by people with knowledge of these PSMA radiopharmaceuticals:

europeanurology.com/action/...

This article have info about AC 225 PSMA after treatment with Lu 177 PSMA:

sci-hub.st/https://www.scie...

[WhiteStrat in reply to tango65]

thank you.

[tango65 in reply to WhiteStrat]

I added other article with more info. Best of luck!!

[WhiteStrat in reply to tango65]

Thank you, again. One of the authors of this article is my doctor in Munich, Dr. Eiber.

[tango65 in reply to WhiteStrat]

I have been in touch with him. I had Lu 177 PSMA treatment at the TUM in Munich .

[Tall_Allen]

You should also have an FDG PET scan. If you have significant tumor tissue that does not express PSMA, destroying the ones that do still express PSMA may clear the way for accelerated growth of the rest. Worth checking first.

prostatecancer.news/2019/12...

[4Rosebud]

have you had a firmagon injection to stop the psa...what is your testosterone level...check it first.and then get firmagon shot.

my psa was 199 and doubling every 2 weeks 3 years ago I'm still stage 4, and psa in low 20's

[WhiteStrat in reply to 4Rosebud]

thank you. my testosterone is below 3 at last count (still hate writing that) a few weeks ago. I had firmagon a few years ago but now I'm back to lupron. In addition to Ac-225, I'm exploring PARP inhibitor and immunotherapy with Dr. Dorff at City of Hope in LA.

[4Rosebud in reply to WhiteStrat]

whats your doubling time... how long have you had pca. I know this sounds crazy but I'll say it...no never mind..most of the folks here seem to think alternative things are voodoo or something ...do you have hi blood sugar...check your blood work to see...anyway some people are using metformin which is used for diabetis to lower blood sugar and slow the cancer done because cancer uses sugar as fuel.

[Patrick-Turner]

I had 4 doses Lu177 between Nov 2018 and May 2019. By Nov 2019, Psa had gone from 25 to 0.32, and scans showed elimination of nearly all soft tissue mets, with huge reduction of bone mets. But by July 2020, Psa was back up to 30,and I had 2 more doses Lu177 and Psa went down to 7. Now Psa is back up to 30. During the discussions with the boss doctor at Theranostics Australia, he did mention use of a small % of Ac225 with Lu177, but didn't insist on it, and the PsMa scans last November showed that many bone mets were reduced but some new ones appeared with low SUV for Gallium 68, which meant it was pointless having more than 6 doses of Lu177. So the theranostic treatment with nuclides has a fundamental flaw because it depends on PsMa expression at Pca mets, and over time, Pca mets mutate so little PsMa is expressed thus the Pca avoids being killed by Lu177 or Ac225. Ac225 has worse side effects on tear glands and saliva glands. I get a slightly dry mouth while out on a 70km cycle ride when its 35C, like today, and I have no problem with tear glands. Its seems I just have not had as many side effects which have affected other men who have had 6 doses of Lu177.

PsMa expression varies depending what else is used against the Pca. There are things about nuclide treatments that are not known, and un-predictable.

I was diagnosed 2009 and probably had Pca begin in 2004, so my Pca is about 16 years old, so its beginning to become more than one type of Pca.

But recent PsMa scan could still not see any soft tissue mets, and FDG-PET scan last July was also negative. So because I now appear to have only bone cancer, my onco has referred me to a doctor who gives Ra223 which only works on bone mets and its action is based on calcium traffic at mets. So all the bone mets with high or low PsMa expression should be able to be zapped by Ra223 alpha particles.

I have yet to meet this doctor, and discuss the whole process.

But the only other option would be Cabazitaxel with maybe some Carboplatin. It seems many here really hate having chemo, but I got through 5 doses Docetaxel in Mid 2018 and I used to cycle 17km over to hospital to get it. I have nearly recovered from the lazy leg thing of neuropathy, made worse because in Feb 2017, I had both knee joints replaced. I could cycle but walking was agony, but my bike speed I had 5 years ago has come back now.

I was once called "the man they could not root, shoot, or electrocute" but here I am at 73 and still cycling 200km+ per week. However, very few other men my age have anything like my athletic capability, and methinks they are very prone to having a much worse time with chemo or ADT, or other Pca treatments. It would be unfair for me to suggest they take up cycling because in many places they would soon be flattened by motorist traffic, but going to a gym where they raise a good sweat for an hour a day might help them. And for men 80+, any sort of getting fit with exercise might cause more problems than it solves.

I've cycled about 145,000km at least since 2006, so I have become hardened to cycling 70km in 3 rides per week.

I have almost no idea if Ra223 will work to give me more years of life, but If I just quit all treatment now, I'd get real sick real soon, judging by speed of Pca rise.

Patrick Turner.

[Cleodman in reply to Patrick-Turner]

Just a correction. Ac 225 does not target PSMA. It targets h2k receptors instead. So it still may be a viable option for low PSMA avidity lesions.

[Patrick-Turner in reply to Cleodman]

Thanks for the correction. I'll check that out, but when docs giving me Lu177 mentioned they might include some Ac225 with Lu177 back in 2019, they did not say Ac225 was not dependent on PsMa targeting. For what I have read, Ac225 can act "more powerfully" on all Pca mets, but with much worse side effects. So the the idea then was to pursue Pca with Lu177, and it took 6 doses to get to where I am now, which includes the fact that some bone mets are not making much PsMa expression, and not enough to give more doses. My oncologist talked to the doc giving Lu177, and Ra223 seems like a good idea. It is doubtful that I would have trouble with Ra223 side effect of brittle bones breaking because bone mets are small and not yet big enough to wreck my bone strength.

I will be getting Ra223 earlier than many men who expect miracles when their Psa is 1,000 and they have very bad pains from bones because their Pca is much more advanced than mine. The only way to live a long time with aggressive Pca like mine is to act asap without any dithering around, or hoping that chemo will work, while ignoring all the scans and Psa rise which tell a man it is not working.

I have heard that in Germany, Ac225 is being given in a small % added to Lu177.

I also recall the early research that was done with Ra225 and it seemed like a truly miraculous nuclide for Pca treatment, but I don't know if its been widely approved anywhere. It is available here in Australia from Theranostics Australia, but conditions for its use are stringent, it would seem.

I see no reason to not use Ra223.

Patrick Turner.

[Patrick-Turner in reply to Cleodman]

I just looked at the article ncbi.nlm.nih.gov/pmc/articl... says nothing on h2k receptors but does mention PsMa targeting.

Many nuclides are now being used for a variety of cancers, and perhaps some generate h2k, but PsMa is only made by Pca mets, afaik.

Where did you find out about h2k?

Patrick Turner.

[Cleodman in reply to Patrick-Turner]

I was discussing my options for targeted radionuclide therapy in the United States with a Dr. Nordquist based out of Omaha, Nebraska. He is clinical trials only and mentioned that Ac 225 might be a better option since his next trial with Lu 177 is unknown.

Here is his email quote

“Without PSMA imaging available (except UCLA & UCSF) or on some clinical trials. I have a patient getting a free PSMA PET at Univ. of Michigan on trial. I would probably recommend the Ac225 alpha emitter that targets hK2 and not PSMA. All of my radiopharm are on clinical trials which are at no cost. I currently have trials for Th227 (PSMA) & Ac225 (hK2). My last Lu177 PSMA closed but several more Lu177 PSMA trials opening soon.”

[Patrick-Turner in reply to Cleodman]

Well, afaik, the use of Lu177 depends on PsMa expression and on the invention of ligand method by Novartis, which may well be owned by European business. Lu177 is a potentially a very big "disruptor treatment" it would damage the very lucrative business of giving chemo, which does not have a great deal of long term success with Pca. My guess is that the reason FDA have not yet approved Lu177 is that many Big Pharma businesses don't want it to happen even if Lu177 gives more years to Pca patients than what BP currently provides. If USA BP companies owned the Lu177 ligand chemical process, maybe FDA might have approved it, and then you might see big increase on the price paid in Germany where Lu177 treatment was invented.

I recall initial trials and tests of Ac225 were in USA, and I cannot recall any mention of hk2. But initial use of Ac225 seemed to be quite miraculous, with all small to large mets in the body plus the Pca at original PG all blasted to bits better than Lu177.

So why is Ac225 not used instead of Lu177?

I can only point to side effects. It may not matter what chemical is used to target the nuclides, the docs can or cannot target to a range of cancers, or they cannot. What matters are the efficacy of treatment, side effects, reliability of producing Ac225 and any ligand or targeting chemical, regardless of what that is, and the cost, and availability.

The doctor here running Theranostics Australia must have had good reason to limit my treatment to 6 doses Lu177. He told me in 2018 that a man in Germany had 10 doses. Another man who was in Lu177 trial at Peter Mac in Melbourne in 2016 said he had 7 doses. I have no clue at all what the details were for the medical history of those two men was, or how they fared years later. None of us patients get to read just how long all the other patients last who have these new fangled nuclide treatments.

I am guessing that I may have had a bigger Pca reduction if I had had Ac225, and maybe needed only 3 doses to get where I am now, but I am fairly certain I would have a permanently dry mouth, and need to squirt artificial tears into my eyes from a bottle.

But I am telling it all just as it is for me, complete with unpleasant details.

I wish chemo could be targeted to Pca in similar way to how Lu177 is targeted. This would allow far small doses of chemo, and it would only affect the Pca, and be much more effective. At present, chemo is a really primitive treatment, where we poison the whole body just to kill a few cancer cells, which often just won't die.

I live in a world where I can only get what is available, and what docs think might give me a useful extension to my lifetime.

I really hope you get access to trials or treatments with good probability of extending your lifetime.

Patrick Turner.

[GP24]

Ac 225 causes more side effects than Lu177. Dry mouth is the main problem. This study reports: "Xerostomia persisted during follow-up."

sciencedirect.com/science/a...