Why to wait with LU177/AC225 until all other things fail ?

[Emmaduxy]

Hello to all at this very helpful forum!

I’m new, making research for my father, was reading a lot, but that is my first question here.

What is the reason why new and (as it looks from trails) effective treatments like LU177 AC225 and only recommended and offered to those who have used and failed on everything else ?

Especially when many trails show that the best results were achieved on treatment-naive patients ? Those (in trails) who had no therapies before had the most remarkable response to this treatment.

It is also known that usual treatments are only palliative. And all patients will become resistant with time and the problem will grow on.

With all these obvious facts still doctors practice is to use everything on a patient before advising him alpha/beta particles option.

Eg - a patient diagnosed with stage 4 PC, Gl 9-10, PSA over 500, large locally advanced tumor, surprisingly without mets yet. All doctors advise to use ADT first and wait until he becomes resistant, then to go for chemo. And only after all this fails only then to think of LU /AC treatment. Even saying - “wait for mets to grow”. Sounds strange to us.

We tried to ask doctors - WHY, why to wait until things become worse ? May be there any adverse effect for this treatment at the moment when just diagnosed, but not treated yet ? Though trails, especially South African trail show the opposite. We did not get an answer (asked several) that will explain the actual reason.

So this question here - any ideas - why they all say to wait and use other things ?

Asking on behalf of my father. Thanks in advance.

[GP24]

I am not aware of trials that show that the best results with Lu177 were achieved on treatment-naive patients. This were observations in clinical practice that were reported in articles, but no trials.

The Lu177 therapy is not approved by the FDA nor in Europe. There are no long term randomized trials yet which are required to get this therapy approved. If there is a therapy that is not approved and no long term results are available for it, the recommendation will always be to use this therapy after all approved therapies have failed.

In Germany it is done on a "compassionate use" base although it is not approved. Doctors observe in their clinical practice that it works well and has few side effects. So they continue to treat patients with this therapy.

In your case, if there are no mets, this is no case for Lu177. You treat what you see on a PSMA PET/CT scan. If there are no mets you see nothing, except the tumor in the prostate. If the patient has no mets I would have surgery.

[snoraste]

One explanation may be to use the standard ammo for as long as possible to extend longevity, given the limited number of medication in hand, and then tag on the Lu/Ac at the end. Another (at least in the US) is fear of malpractice lawsuits.

If you do not show any mets under PSMA scan, or your PCa is not PSMA-expressive, the treatment will not be effective. As someone else said, a combination of radical prostatectomy, radiation and ADT maybe the first line of attack for you and may keep the beast at bay for a while (or even lead to a cure). But I, for one, agree with earlier introduction of Lu/Ac in a metastatic setting and am planning on using it while I'm still hormone sensitive.

[AlanMeyer]

Here is a report of a study of early treatment with Lu-177 that appears to confirm Emma's reading that treatment naive patients did better than those who had prior hormone and chemotherapy. I say "appears" because there are so many ways to get these things wrong and I don't know how well vetted is the study or the report.

snmmi.org/NewsPublications/...

Of course these are all men who were known to express a lot of PSMA. Those who don't won't see the same results.

[GP24 in reply to AlanMeyer]

Alan,

I did a successful very early PSMA therapy with Lu177 myself, so I am not against early PSMA therapy, I am all for it.

In my post I tried to provide an explanation for Emma's question.

The study you mention has now been published in the Journal of of Nuclear Medicine this year:

jnm.snmjournals.org/content...

They made a retrospective study based on the patients treated so far at the Bad Berka clinic. I believe the results are very interesting and most probably could be verified in randomized, prospective studies. But currently this study will not impress the FDA or a guideline committee.

[Moespy in reply to GP24]

GP24,

If you don't mind sharing, all in how much did it cost for treatment and expenses?

For me, affordability might be a consideration. Until this treatment is approved in the U.S (and other areas of the world) I think some of us will have to wait.

Thanks,

Jim

[GP24 in reply to Moespy]

gyancey mentioned $13.000 for one cycle plus travel expenses. You usually need at least two cycles.

healthunlocked.com/advanced...

[cesanon]

Lu177 takes a toll, especially on kidneys and salivary glands. They Generally will give no more than 8 treatments.

It is something to be held in reserve, not something to lead with.