Xofigo after Actinium225?

[Zolababs]

Can one receive Xofigo following Actinium225 treatments?

[Tall_Allen]

Good question. Th-227-PSMA is sort of similar to that sequence. It is in clinical trials now. My guess is that it depends on how extensive bone metastases are, whether it's infiltrated the bone marrow, and how your blood work looks.

[Patrick-Turner]

I had 6 doses of Lu177 in 2019 and 2020, and that seems to have killed all soft tissue mets in many lymph nodes. But it didn't kill all bone mets, and after the 6 x Lu177 doses some small new mets in bones appeared which had very low PsMa expression, so having any more Lu177 was seen to be useless. This could have happened with a lesser number of doses of Ac225. Both Lu177 and Ac225 depend on PsMa expression to work.

PsMa expression is a fickle thing, and it varies depending on the Pca stage and what is being used to try to slow Pca growth such as ADT, Zytiga, Xtandi etc.

Chemo before my Lu177 didn't work, but was thought to re-sensitize my Pca to Xtandi or Zytiga, and for about while having Lu177, Xtandi worked to get Psa low, and maybe boost PsMa expression, and it worked for 8 months, so I doubt it boosted PsMa expression for my 5th and 6th dose Lu177.

So last October when I had the 6th Lu177 dose, and Psa went down to nadir of about 7.5 then began to increase and its now about 200.

I had full blood number examination to check on bone marrow function about a month ago and I had enough function to allow use of Ra223 to work on the bone mets. There was no other nuclide which could have worked on mets with very low PsMa expression.

So last Friday, 26 Feb 2021 I had first dose of Ra223 and it does not rely on PsMa expression but targets itself to mets where any calcium traffic is going on, and it is supposed to be good on very small mets, and I have a lot of them.

My doc said my bone mets were in my bone marrow where it loves to live and grow.

Ra223 as an alpha particle emitter, the particles travel a short distance in marrow where bone mets are, so damage is done to met DNA and to the local nearby bone marrow.

So now it remains to be seen if I can have enough doses, maybe 6, of Ra223 to kill all bone mets and have a large enough amount of healthy bone marrow left over to allow normal life.

If this was the case, then theoretically more Ra223 could be given next year, but doc told me that the marrow destroyed by Ra223 won't re-generate and I could not expect to have a bone marrow transplant.

Men with very high Psa and very large mets causing pain and bones to crumble may not be able to have enough Ra223 doses. This is why Ra223 is often considered to be palliative care, with mean extension to life of only 4 months. But I am getting Ra223 with fairly small bone mets, no symptoms of Pca. It seems my bone mets make much more Psa, but alko phosphates have not gone real high. When diagnosed in 2009, I had Gleason 9 which was so locally advanced the urology surgeon could not operate, yet Psa was only 6.

I cannot read the future, but if all goes well I end up with no bone mets, no visceral mets, so technically I would be cured, but that seems too good to be true and there's a possibility that my present bone mets spread mets to lymph nodes weakened by previous Lu177 and maybe straight into organs, lungs, liver, brain, wotever.

There is also a risk of leukemia where bone marrow becomes defective.

The alterative was to have Cabazataxel which is only marginally more effective than Docetaxel, and it probably would have failed, allowing Pca to damage bone marrow so much that nothing else could work, and that could be time to raise a white flag.

Patrick Turner.

[Zolababs in reply to Patrick-Turner]

Thank you so much for your reply. My husband was first diagnosed in 2004. He has been through the gamut of treatments beginning with radical prostatectomy, radiation to prostate bed, hormone therapy, Zytiga, Xtandi, and chemotherapy. (He had a great run with Zytiga-nearly four years.)

Following the failed second variation of chemo, our oncologist urged us to go to Germany for Lu177. My husband had a PSMA scan and it revealed PSMA was not well expressed by the cancer in his soft tissues. In searching for an alternative treatment, we heard about an Ac225 clinical trial that utilized hK2 to target the prostate cancer cells instead of PSMA. We opted to go that route and my husband was the third patient in America to be accepted. Unfortunately, we had to wait six weeks until his first treatment, and during that time, his PSA exploded and his bone scan approached Superscan status. His first Ac225 treatment was on January 29, 2021. Since then, he has suffered multiple rib fractures, vertebrae compression fractures, and a fractured sternum. Thankfully, the trial bosses are allowing palliative radiation. In the last two weeks, his PSA has gone from 638 to 980. (Difficult to believe it was 76 in November 2020.)

Glad to know we could possibly utilize Xofigo following Ac225 treatment. Thanks for sharing your story. Sending prayers for your treatment success.

[Patrick-Turner in reply to Zolababs]

Hi Zolababs.

I have not learnt anything about Ac225 with hK2 targeting which may allow Ac225 and maybe other nuclides to go to bone mets which have very low PsMa expression.

I'll have to read up a bit more. But your man's condition is most unfortunate because when bones start breaking he must be feeling just terrible. My Psa was just 7 before last November, and now is 200, maybe, But I have just begun Ra223 a week ago, and I've been doing heavy pick and shovel work to dig a drain to stop storm water flow from next door flooding my carport. So far so good, and although this does not agree with my bit of osteo arthritis in lower back, I have been pain free after the efforts, which I limit to about 2.5 hours because I have time, and other interests.

I just might have been able to get Ra223 just in time before bones started to break.

Although Psa is zooming up, or was, My alko-phosphate levels didn't indicate high bone mass loss. I think my Psa has mutated to emit much more Psa than the original type of Pca that had not seemed to mutate until last year. One problem with all Pca treatments is that not all original Pca is ever killed by any one treatment, because whatever is used may not reach some places in bones or elsewhere in sufficient quantities to kill all Pca clls and they react by mutating to oppose each form of treatment, and its these Pca cells that become the major threat later. I could see that in PsMa scans after 6 doses Lu177, but Lu177worked well afaik on soft tissue mets so I qualified to get Ra223.

Afaik, Ra223 does not have side effects of dry mouth and eyes that Ac225 causes. Lu177 also gives same side effects but its not as bad as Ac225.

I am OK after 6 doses Lu177, but docs worry about my bone marrow function because when Ra223 goes to bone met sites which are usually all within bone marrow, it should destroy Pca, but will also destroy some local bone marrow. My thinking is to get Ra223 before bone mets have become big enough to weaken the hard outer layers of bone which give our bones the strength we need to go about life. I will lose some bone marrow, but maybe I will be OK because most of us have enough bone marrow function to exceed our minimums for health.

When docs do replacement knee and hip joints, they drill down into leg bones to insert tapered shafts of titanium, and this is a very traumatic action on bone marrow, some of which is lost, but men with both knee and hip joints replaced, loss of bone marrow is not considered any threat.

Every Pca patient has reason to fear the time when his Psa just suddenly takes off, and it seems untreatable, but there are cases where some have had Psa whiz up to 1,000, then become almost undetectable, when just the right treatment is used, and some men have had this happen several times over a 10 year time after diagnosis.

Let us all hope the Ac225 goes well. But the bone breaks will probably be an ongoing bother even if all Pca cells are killed by Ac225. There's only so much docs can do to install titanium strips and rods and and screws to hold a skeleton together, and then there would be restriction of movement. Spinal re-constructions are difficult to get right, and probably eye-wateringly expensive, if you could arrange it.

Its a nice day here, a nice arvo coming up, after I drive out to get lunch at a cafe.

Take care,

Patrick Turner.

[Zolababs in reply to Patrick-Turner]

I will be anxious to know how your treatment goes. Best of luck to you!