2nd LU177 treatment coming up in TUM 27/05 increased PSA

[Jenbt]

Within 4 weeks we have seen a PSA climb of 28, a bit disheartening. We are now considering coming off Xtandi for the 2nd cycle to increase testosterone and tumour avidity...any thoughts?

[GP24]

Xtandi may increase the PSMA expression. Therefore I would continue with Xtandi.

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[The_Don5 in reply to GP24]

its back to the same old argument does more circulating testosterone due to stopping xtandi provide greater tumour avidity and more scope for the lutetium to work?

[GP24 in reply to The_Don5]

Why do you think Lu177 works better when there is greater tumor avidity? What I can tell PSMA expression is the main factor. That is why they call it PSMA therapy.

[The_Don5 in reply to GP24]

Yes Psma is what lutetium attaches too, that's the theory of TUM since 2014 take it up with them :). How many studies actually show increase of PSma with 2nd line hormones. the only determinant that I could see would be psma pet with 2nd line hormone followed by one without in the same individual but then you have to take into consideration increase in disease burden and that increases psma also?

[GP24 in reply to The_Don5]

The increase in PSMA has been observed in mouse studies. The following study, however, reports the result with humans:

euoncology.europeanurology....

[The_Don5 in reply to GP24]

but does this equate to a body of evidence and secondly some patients with psma avidity still don't respond to lutetium so does this mean there are more factors at play than simply psma expression ?

[The_Don5 in reply to GP24]

Also this study is based on initiation of first and second line ADT it doesn't detail or investigate psma expression in patients with longer term use ...

[GP24 in reply to GP24]

I wrote: "Xtandi may increase the PSMA expression". There is no body of evidence for that, just mouse studies and this study with a few patients. That is all I have, but I personally believe in it.

The following study looked at long term ADT use and found a decrease in PSMA expression for long term use:

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

So Xtandi or bicalutamide seem to cause a short-term increase in PSMA expression.

[The_Don5 in reply to GP24]

Yes agree that is the study i had seen in long term use. I wonder what is quantified as short term in terms of time in the study with ADT and when does it begin to dip. Could i ask if you have personally combined the two or is your belief based on articles above or other ancedotes?

[GP24 in reply to The_Don5]

From the limited evidence that currently exists, you can only assume that there is a flare of PSMA expression for about four weeks or a bit more. Probably depends if antiandrogens are used or just Lupron. The mouse studies indicate a better result with antiandrogens such as Xtandi or bicalutamide.

My friend and I start to take bicalutamide two weeks before a PSMA PET/CT or a PSMA therapy. Prof. Baum recommends Xtandi, however, we are both not resistent yet, so the insurance will not pay for that.

My friend said, "you see more than you ever wanted to see" when you combine bicalutamide with a PSMA PET/CT. The result of my PSMA treatment was considered "exceptional" by Prof. Baum.

Bottom line, you can say "I do not believe in that" or just give it a try.

[Jenbt in reply to GP24]

Did you continue these throughout Lutetium cycles? Or was it just for the purpose of the scan?

[Jenbt in reply to Jenbt]

A lot of German hospitals are ok with first line ADT but not second line ADT in conjunction with LU177 therapy

[GP24 in reply to GP24]

As an "exceptional responder" I had just one cycle and all mets were gone. I continued bicalutamide from the PSMA PET/CT through the first cycle and then continued with bicalutamide for five months after the Lu177 treatment. The latter was my personal interpretation of the GETUG-AFU 16 study which recommends six months of ADT after salvage radiation for better results. My hope was to delay the recurrence after the Lu177 cycle.

[Jenbt in reply to GP24]

But most are already on first line adt leading up to lutetium I guess the more unique aspect of your treatment was that you received lutetium in the hormone sensitive stage. Not all hospitals will treat at this point

[GP24 in reply to Jenbt]

Almost no hospital will treat in the hormone sensitive state. Most accept patients after Docetaxel treatment or at least after Zytiga failed in CRPC.

In that case you can try Xtandi instead of bicalutamide.

[The_Don5 in reply to GP24]

XTANDI Isnt funded in the hormone sensitive state, it is similar to zytiga in that respect.

[Jackpine]

Jenbt,

I wouldn't be too concerned a about a PSA rise just yet. After my first injection I had a 40 point drop in PSA after 2nd it went up 25 points then after third down to 25 and by 4th down to 0.4.

I did stop taking Zytiga and prednisone after talking to my OC.

I personally had wonderful results but I know everyone responds differently. Hoping for wonderful results for you!!

[The_Don5 in reply to Jackpine]

what was your mo reason for stopping zytiga?

[Jackpine in reply to The_Don5]

It had stopped working so he stopped and I was fine with that..

[j-o-h-n]

Let's remember our fallen military heroes this Memorial Day and always...

j-o-h-n Saturday 05/25/2019 12:38 PM DST

[Mohopes]

My husband had his first dual Lu-177/Ac-225 treatment on May 16 in Heidelberg. The doctors there told him that initially his PSA might go up because of all the dead cancer cells circulating in his bloodstream so he shouldn't put too much weight on his PSA score after one treatment. A bit scary, I know, but I figure the people there pioneered this treatment and should know what they're talking about. In my husband's case they are expecting his PSA to go up because he has an anomaly they really haven't seen before: VERY high PSMA avidity with cancer spread all throughout his bones, lungs, lymph, and prostrate but a relatively low PSA after six cycles of chemo. Did your husband's doctor say anything about the dead cancer cell phenomenon?

[The_Don5 in reply to Mohopes]

see reply .

[The_Don5]

excellent question IT candy. we started to reduce xtandi this time with a view to complete absence during lu 177. last time once we resumed xtandi we saw a downward slump on first cycle of lu177 whether this would have happened Regardless of xtandi who knows or whether this was the renewed side effects of xtandi taking place again ? My question remains does the interaction of these drugs support lutetium; the psa levels rose in first cycle . We will be following TUM advise on this cycle letting the testosterone run free so nothing is masked. Rightly or wrongly we will see.......

[The_Don5]

Interesting, I love the way Heidelberg combine the alpha and the beta treatments esp in a patient with extensive bone mets.. We are in a very similar situation with extensive in bones lungs lymph and prostate though Technical university munich will initially roll with lutetium alone to mitigate the more serious side effects of actinium 225 and then introduce actinium (hopefully) once lutetium has gone as far as it can go. how were the side effects from the combo treatment? any salivary gland issues? is heidleberg the only hospital combining actinium and lutetium I wonder?

[Mohopes in reply to The_Don5]

The side effects have been much more pronounced than anticipated and worse than chemo. My husband was fine for two days following the treatment but right before we got on the plane home—of course!—he was overcome by nausea, vomiting and diarrhea. The German doctors were very stingy with the anti nausea drugs, only two pills, but that was enough to get him home. Since then he has suffered extreme fatigue, flu like symptoms, depression, some intermittent nausea and diarrhea, and just in the past couple days some dry mouth. Rough going to be sure. But today he is finally feeling a bit better—12 days after treatment. We’ll see if it lasts. My husband is determined to soldier on with these treatments. So, back in July. Oh, I am not sure if Heidelberg is the only hospital doing the combo treatments.

[The_Don5 in reply to Mohopes]

We´ve had vomiting once yesterday immediately after treatment, same as 1st cycle but nothing today- same as first cycle it was a one off albeit we had lutetium on its own. sorry to hear the terrible sides lasted so long the actinium 225 is definitely the harder of the two treatments by the sounds of it. But, as the old saying goes "the best medicine tastes the worst". Here's hoping for some nice results to make it all worthwhile MoHopes. PS were the side effects worse than chemo/docetaxal?

[Mohopes in reply to The_Don5]

Yes, the side effects were worse and David had both docetaxal and carboplatin. However, MD Anderson had him nicely dosed up with prophylactic and post-treatment anti nausea drugs as well as steroids. The first chemo was rough but once they got the timing and dosage of all the drugs down the nausea wasn’t so bad just the overwhelming fatigue. It would all hit from days 3-7 after the chemo drip with the fatigue lasting a bit longer. This radioactive stuff though is much more unpredictable, capricious.

[Jackpine in reply to Mohopes]

Mohopes,

I know the first treatment for me was the worst severe fatigue, no appetite, nausea, lots of bone pain, it lasted about 5 days then I started to feel better. I think being sick is a good thing as I feel it’s thevdrug doing what it’s supposed to be doing.

Hope for great success!

[Mohopes in reply to Jackpine]

Yes, I think he had bone pain initially and in the places with the worst metastases so maybe that is a good sign!

[The_Don5 in reply to Mohopes]

Maybe tumor flare up due to lu and act ? i hear this is common. We are experiencing fairly heavy fatigue today 2 days after infusion.