Here is a small study which observed increased PSMA expression when Xtandi was combined with an Lu177 therapy. The researchers expect Lu177 to work much better in combination with Xtandi. link.springer.com/article/1...
This were just ten patients but all of them showed an increased PSMA expression.
It only lasts for 3 months, then there is a decrease in PSMA expression.
Thanks for posting. it is interesting that the increase in PSMA expression happens even in patients treated previously with enzalutamide until they failed the treatment.
Seven of the 10 patients had failed enzalutamide treatment. This seems to be an acute phenomena . Ten 10 days of enza treatment causes an increase in PSMA expression. This could be used before PSMA PET/CT studies or Lu 177 PSMA treatments.
"This could be used before PSMA PET/CT studies or Lu 177 PSMA treatments."
This is what makes the researchers so exited. Both the diagnosis or theranostic is improved or you can reduce the Lu177 or Ac-225 dose to avoid side effects.
However, it becomes more difficult to remain oligometastatic when imaging sensitivity is increased. I will get a PSMA PET/CT scan on a brand new machine next month which shall detect mets down to 2 mm in size. I do not know if I really want to see these and thus become polymetastatic. SBRT docs will refuse to treat me then. Also they will have trouble detecting these tiny affected nodes with their planning CT.
I read about the new machines detecting 2 mm lesions, similar to Combidex. Where are you getting the scan done? I am going to UCLA to get another Ga 68 PSMA PET/CT at the beginning of February, but the equipment is not new.
Best of luck, my friend
Tango
When I had my 4 shots of Lu177 between Nov 2018 and May 2019, I happened to be lucky to have a research Dr Louise Emmett look after me for the 3rd shot of Lu177. She was doing some clinical work with Pca patients while waiting for funding to be approved for her next trial at St Vincents Hospital in Sydney for combining Lu177 with Xtandi. She believed that the chemo that most men had before Lu177 re-sensitized their Pca to Xtandi or Zytiga , and she had noticed that men who were taking Xtandi often got a better result with Lu177 than if all they had was Lu177. Anyway, it seemed she became aware that Xtandi increased PsMa expression, so that as Lu177 therapy proceeded, the SUV for Ga68 in scans and for Lu177 in therapy became higher, thus making Lu177 much more effective. She cited cases where men got a far longer period of low Psa with Lu177 augmented with Xtandi. So after my 3rd shot of Lu177 I began taking Xtandi and it seems that aided the action of previous doses of Lu177, and after the 4th dose of Lu177 my Psa plummeted, and was 0.32 last November. I had begun Lu177 a year earlier with Psa of 25, with countless mets in soft lymph node tissues and bones. Biggest bone mets were 1cm dia. Not big enough to cause fractures, but big enough to cause discomfort.
The follow up PsMa scan in August showed no soft tissue mets, no new mets any where, and bone mets healing, and no mets in CT that were not also seen in PET scan.
I had been on Xtandi for 3.5 months, with 4th Lu177 dose included, so seems to me Dr Louise was right to suggest I take Xtandi, and although I didn't have Xtandi for all doses of Lu77, it seems like I am getting a benefit still, because I'm continuing with Xtandi, although at slight lower dose of 3 capsules a day instead of 4.
Dr Louise had her funding for a trial of Lu177 + Xtandi approved a day after I met her, and I am not sure yet of the results of conclusions of that trial.
But I have heard of other cases where men have had chemo after Xtandi or Zytiga stopped working, and so they ceased taking these drugs a month before chemo began, and if chemo failed, it still re-sensitised the Pca, and if they didn't have following Lu177, but re-commenced Xtandi or Zytiga, then these drugs would work for a much longer time than their initial average time of about 8 months. So when hormonal manipulation with ADT + the ad-on drugs stops, the chemo may renew the ability of the add on drugs to work again. This is not universal for all men. But for some lucky men, seems like it happens.
I had to pay usd $27,000 for my Lu177, but Xtandi ain't cheap, but that costs me usd $ 4.40 each month at a chemist because its covered by Australia's Medicare PBS scheme. Lu177 is not, so I had to find the dough for it.
I cycled 50km this am, and averaged 24.1 kph for first 17km across town to have a coffee at Canberra Hospital, because the café there is open to all very early, and I'd left home at 6:30, when it was cool. That average speed is very good for an old 72yo man much affected by the procession of medical treatments including chemical castration since 2010, and 5 rounds of chemo, that have had the worst effect on athletic ability. And 7 weeks ago I had a small bowel blockage due to adhesions. I was in hospital for 11 days, has a minor op and I lost 8Kg, but am now cycling very well having put 3 Kg back on. There are no symptoms of Pca. The dry mouth side effect from Lu177 seems to be getting less. The stomach problem did cause anemia, so I have had to eat some red meat for awhile. I am getting stronger and faster on the bike.
Don't ever give up folks.
Patrick Turner.
Thank you for your post. Informative and inspiring. Keep on truckin- I mean bikin
Thank you for your post. Dr. Emmett published the results of a study regarding the impact of ADT on a PSMA PET/CT last year.
"Continuous long-term ADT significantly reduces the visibility of castration-sensitive PC on PSMA PET/CT. If the objective is visualization of the maximum possible extent of disease, we recommend referring patients for PSMA PET/CT before starting ADT."
ncbi.nlm.nih.gov/pmc/articl...
"In our cohort, no PSMA expression flare phenomenon was detected on follow-up PET/CT scans at a median follow-up of 3 months. However, an early and short-lived flare cannot be excluded."
In the study I cited the patients took Enzalutamide for a mean duration of 11.8 days only before the PSMA PET/CT to determine the increase of the PSMA expression.
So taking Xtandi for 12 days will be sufficient to get an increase of the PSMA expression for diagnosis or therapy.
The mean duration of medication with enzalutamide was 11.8 ± 8.1 days. The mean time between baseline and follow-up PET/CT was 14.4 ± 7.3 days.
It’s important to note that in the study the subjects were all castrate resistant. I’ve done some reading on this, and it appears xtandi generally improves uptake for CR patients but not hormone sensitive ones (or at least it’s equivocal for HS pts ).
Where did you read this?
pubmed.ncbi.nlm.nih.gov/305...
They had 2 cohorts: crMPC and hsMPC, the crMPC cohort all had increased PSMA with abi or Enza, but the hsMPC cohort all initially had a declined in PSMA, with Lupron and casodex but later 35% had an increase
Thank you Bruce. Based on the previous xenograph studies I was convinced it would make no difference being hormone-sensitive or not. I also could see no reason for a difference. The trial says it is hypothesis-generating but it does not offer a hypothesis which could explain the findings. However, because all hormone-sensitive patients had a decline in PSMA expression I see no real need to wait for larger studies before applying the results for now.
I had taken Bicalutamide without Lupron before my PSMA PET/CTs and a Lu177 therapy expecting this to increase the PSMA expression. The study does not really apply to Bicalutamide without Lupron but now I am unsure whether I should continue with that. I am hormone-sensitive.
Basically, as I see it, if the casodex reduces the cancer (HS disease), it will reduce the PSMA. In CR patients, anti-androgens do not reduce the cancer, by definition, so the stimulative effect is able to occur.
When do Xtandi side effects show up?
New Scans after LU177 treatment
How long does it take for xtandi to be effective?
More information on Lu PSMA treatment failure
