New radiopharmaceutical (Ac-225-PSMA-617) has high rates of remission in early trials

[Tall_Allen]

Ac-225-PSMA-617 is an alpha particle emitter that targets prostate cancer cells. Lu-177-PSMA-617 is a beta particle emitter that targets prostate cancer cells. Alpha particles have shorter range and more effective cancer cell killing. This small trial (n=17) in South Africa was among chemo-naive patients:

pcnrv.blogspot.com/2018/01/...

[JaybeeAndGG]

Wow. That is promising indeed. As always, thanks for sharing with everyone Allen.

[cesanon]

Allen

Bayer's product is an alpha emitter as well, is it not?

Though it is for bones only.

Still, have we learned anything from their trials that would support the early indications here?

[Tall_Allen in reply to cesanon]

That's right. With Xofigo, we've learned that earlier is better (more effective, less toxic). Heavy bone marrow involvement is a contraindication.

onlinelibrary.wiley.com/doi...

ncbi.nlm.nih.gov/pmc/articl...

[Lombardi24]

Doesn't one need to test positive for PSMA? If the cancer cells don't express this specific antigen the therapy wont work. Correct? According to my onc not all pros cancer cells produce this antigen. Promising though. Onc stated that they can scan for PSMA using a PET scan.

[Lombardi24 in reply to Lombardi24]

Thx Tall_Allen.

[Tall_Allen in reply to Lombardi24]

About 95% of prostate cancer cells express PSMA. Some types (like neuroendocrine PC) do not. They used Ga-58-PSMA-617 PET/CT to monitor radiographic regression in this study.

[Lombardi24 in reply to Tall_Allen]

What about intraductal? Two of the cores biopsied showed intraductal.

[Tall_Allen in reply to Lombardi24]

Yes, IDC-P is positive for PSMA

[Lombardi24 in reply to Tall_Allen]

Thank you

[tarhoosier]

Less pre-treated patients in the South African study responded particularly well. What is the reason for their success compared to the much more treated patients in Germany? Is there a difference in the tumor that resists radiation for those with prior chemo and androgen blockers?

[GP24 in reply to tarhoosier]

South African patients present much later than German patients. Here is a patient who already had a big lump at his neck when he presented. It says on the image: "drug naive patient". So apparently he did not have ADT. The PSMA therapy had a very surprising response:

up.picr.de/33884034wk.jpg

[Tall_Allen in reply to tarhoosier]

I think they had the kind of PSA and radiographic response they would have had with first-line abiraterone (not available in S. Africa) or docetaxel. Four of the 17 men had no previous treatment at all. Most (12) had prior ADT, and 3 had prior Lu-177-PSMA-617.

[j-o-h-n]

Thanks!!!

Good Luck and Good Health.

j-o-h-n Saturday 09/22/2018 11:30 AM EDT

[Rmanns]

Thanks, I've done a little reading on trials lately and these two need to be known.

[tarhoosier]

I understand how a hormone treatment, ADT or AR targeted, would have diminishing returns with each new drug but with this infused radiophamaceutical I am still confused how tumor cells would respond better at differing stages. This assumes no previous radiation of any kind.

[Tall_Allen in reply to tarhoosier]

For example, early Zytiga increases survival by at least 18 months in metastatic men who are still hormone sensitive, but only by 4 months in mCRPC who have already had docetaxel. Each therapy selects for cancer cells that are resistant to that (and possibly other) therapies. PSMA-targeted therapies no doubt select for cancers that are resistant to it.

As GP24 pointed out, South African men present at a later stage of cancer progression - they are just less likely to have had chemo or second-line hormone therapy. Cancer undergoes genomic changes as it progresses or as therapies are administered. 8 of the 17 HAD had some kind of radiation therapy earlier.

[Sriyantra]

Looking for contact with anyone who has had this Alpha 617 treatment..I'm scheduled for Jan 24 in Heidelberg and confused about costs (thought it was 7000-8000 total..not per treatment every six weeks?)

Also looking for reassurance about the side effects or what I can expect. I'm currently not doing well in terms of mobility and general well being..low energy..unable to exercise..full widepreadvskeletal metastases..through spine pelvis and shoulders and upper legs.. crazy situation. Thanks a lot!

[TEBozo]

From a researcher friend:

"Those alpha particle emitters destroy the salivary glands. Fine for a guy on his last leg but not for the majority of patients. Hopefully development of the non-radioactive version happens soon. Development of PSMA linked therapies for prostate cancer started back in 1983 at Hybritech in San Diego, then they ditched the program "