Keytruda, Lu-177, AC-225

[joann48]

I remember when Memorial weekend was filled with fun times, barbeques and lots of laughter. Unfortunately, not this year. Jack has been in bed since his third Cabazitaxel last Tuesday. Its not working so we are really frustrated and hope this will be the last one. But then whats next,, I asked about Keytruda and Dr said maybe but would Lu-177 be better or AC-225?? That's it , there are no more treatments/ so we want to be really thoughtful about the decision. Any suggestions?

[Tall_Allen]

Keytruda is useless except in those with a rare mutation called MSI-Hi/dMMR. I think radiopharmaceuticals may be a good choice.

[Patrick-Turner in reply to Tall_Allen]

You may have read more than I have about the trial of Lu177 with Keytruda which is soon to begin or or which already has begun. But the idea is that the radioactive effect on Pca has the ability to make the cancer more unlikely to hide from a number of drugs including enzalutamide, and maybe abiraterone and ketruda. One has to ask why does the cancer manage to escape the effects of these drugs after there was a good initial Psa reduction, a good response? Just why don't some drugs work in one man and not in another? Well, nobody knows the full answer yet.

In my case, I had a good initial response to Lu177, and Psa dropped from 25 to 5 after 3 infusions, and I had a research doc look after me at the 3rd shot Lu177, and she said that I'd do well to begin taking enzalutamide asap and so by the time I got my 4th shot Lu177 I'd been on enzal for 6 weeks and the idea is that the enzal increases PsMa expression of my doubtful cells and thus attract more Lu177, thus get more cancer killing, and end up with the effect of Lu177 becoming supercharged. She's just been given a grant to begin a trial on this at St Vincents in Sydney. I guess she and a few other docs have seen this effect so often in their practice that the trial may confirm its a great idea to add enzal while having Lu177, because it makes a better result for men who would otherwise get a poor response with Lu177 alone. The docs want to try to squeeze better performance from combinations of drugs.

Anyway, I have a Psa test next Friday and I'll talk to my local onco next week and I'll see if the research doc was right about it. Its the same for Keytruda. The docs need to know as much as they can to do the best for you, and the trials tend to find out more precisely what really works, and how well.

From what little I have read, Ac225 is a more powerful theranostic nuclide than Lu177, but side effects of dry mouth and dry eyes are more likely.

Ppl need to realise that if a theranostic nuclide gets the Pca level to become low, then Psa goes to low, and so does PsMa so when a PsMa Ga68 Pet/CT scan is done it looks like Pca has gone, but for me it means that the Pca has gone below the level of detectability of the PsMa scan. Doctors then say its no use giving any more Lu177 etc because there is no PsMa to attract the Lu177 which will then be just pissed out in a couple of weeks as it becomes less radioactive, and it has not gathered anywhere at Pca sites, so an expensive dose of Lu177 has been wasted. Therefore they'd tell a man he's got his Pca under control, but its not yet GONE, much could still be there, but at a low level equivalent to how things were maybe years before, but it remains a threat, but while this is a small amount of Pca it won't trouble a man so he gets his quality of life back at least for awhile. If the Pca grows up again like most garden weeds do, he can have a PsMa Ga 68 scan and if that shows there's a high PsMa avidity, he can repeat the Lu177, but if he gets symptoms, such as bone pain and PsMa Ga scans show nothing, but other types of CT scans show more Pca is growing, then Lu177 etc would be useless and he has to think about Ra223 or Carboplatin and nothing might work because this is what cancer tends to do; what survives the Lu177, or all the other stuff tends to become untreatable by anything, and the speed of its growth can suddenly speed right up so that no matter what analysis is done the cancer overwhelms the results of say DNA analysis and the treatment is all just experimental, and the chance of anything working becomes tiny, and at that point its time to quit the fight. Just learn to unlive, get your will organised, say tata, and bye-bye. I saw this happen to a man a few months ago, under 60yo, lovely wife, two nice kids.

I'm glad Mr Allen is here to discuss stuff with us.

is Mr Allen Tall ? I'm 183.5cms, and I used to look down on many ppl when I was higher, and I don't mean when I'd had a joint

But as I am getting older, all my bones are getting closer together so I'm having to look up to other blokes more often. And try to listen. I have to listen to a lot of short tubby doctors very carefully

Patrick Turner.

[Tall_Allen in reply to Patrick-Turner]

I think the thinking behind the combination with Keytruda and enzalutamide is different. Because the radiation (from Lu 177) kills cancer cells, their detritus is picked up by the immune system. After getting the "scent" of cancer antigens, the immune system seeks out those antigens wherever they are. It's called the abscopal effect. Another bonus is that Keytruda amps up the immune system that has been depressed by the radiation. This is the theory, at least. When the combination of radiation and Yervoy was tried, it failed to provide an extra benefit - so we'll have to see.

Enzalutamide has been found to temporarily increase the amount of PSMA on prostate cancer cells. (I'll go more into this later) It isn't related to the PSA-lowering effect of ADT.

BTW- the term "theranostic" = therapeutic+diagnostic, was true of Lu-177-PSMA in theory. Lu-177-PSMA puts out gamma rays in addition to beta particles. Those gamma rays can be detected by gamma ray cameras and SPECT in theory. In practice, they just co-administer a PSMA PET indicator which gives a stronger signal. So, Lu-177-PSMA isn't diagnostic or theranostic in practice.

[Patrick-Turner in reply to Tall_Allen]

Well OK, but Lu177 is classified as theranostic generally, ie, "near enough to" when docs here speak about it.

The temporary increase in PsMa is supposed to gather more Lu77 at Pca tumor sites. Yes please, I'll take the enzalutamide if offered. But for how long? that remains to be seen in my case.

Trials now going on for Lu177 + Keytruda are there to answer the question. Yes, Keytruda is an immune booster, got fame with melanoma and breast cancer, and one doc here used it for a gall bladder case and got a remission with a man who got this at 45. Its rare, but a doc does DNA analysis and predicted Keytruda would work, and it did. But the man could not claim benefits on Medicare so he paid the full price, huge, because Medicare would not fund the Keytruda if it is not used for a narrow range of specified cancers.

I don't know full details of PsMa-177, the ligand chemical or the full story about how images are made, I can't claim to be any expert, but it seems docs here know what they are doing. Time will tell what happens to me.

It ain't over yet.

Patrick Turner.

[George71]

I would look into the ARV-110 trial

clinicaltrials.gov/ct2/show...

Local patient is the first in the world to receive prostate cancer drug

By AnaArlene Ramirez

Thursday, May 23, 2019 - 2 a.m.

Nearly 10 years ago, Las Vegas resident Anthony Brasich was between jobs, wasn’t feeling well and was incredibly reluctant to see a doctor.

When he eventually mustered up the courage to see a physician, the doctor discovered a blood clot in his lungs, his prostate-specific antigen count was more than 5,000ng/mL (whereas the normal count is 4ng/mL) and he was diagnosed with stage 4 advanced metastatic prostate cancer.

He was given two months to live and was referred to Dr. Nicholas Vogelzang at Comprehensive Cancer Centers.

Flash forward to 2019: Brasich, 71, is still with us, having been given a number of different treatment options including chemotherapy, immunotherapies, radiopharmaceutical drugs, clinical trials and natural remedies.

Just a few months ago, when a form of hormone therapy left him feeling low on energy, he was ready to try something new. That was a Phase I clinical trial drug known as ARV-110, which targets and destroys androgen receptor (AR), a hormone receptor protein on cancer cells. Genetic signals from the receptor protein are key contributors to a resistence to treatment. ARV-110 degrades AR, thereby regulating the growth signals to cancer cells and controlling disease progression.

In April, Brasich received the first dose of ARV-110, making him the first patient in the world to receive this treatment. Before that happened and as with any clinical trial, there was a rigorous process for Brasich to qualify — including a deep dive into his medical records, scans, PSA counts and blood tests.

Given the nature of a Phase I trial, Brasich must be monitored carefully for any side effects or adverse reactions. During a typical appointment, he takes several blood tests, undergoes EKGs and consults with his physicians before a dose is administered. The drug itself comes in pill form and may be consumed in a matter of seconds. On certain visits, he stays in the clinic for an entire day for continuous monitoring with EKGs and blood collections.

Following his first course of ARV-110, Brasich said he’s feeling much better and believes that the drug is working. Where his last drug left him feeling exhausted and in bed for days, he now has the energy and strength to get outside, enjoy some fresh air, and even take his beloved dog on walks. His first PSA counts indicate a drop, which will certainly be monitored over time.

There is certainly a long road ahead for Brasich as he continues to battle his stage 4 diagnosis. But he’s off to a great start and continues to carry an optimistic attitude — similar to when he was given just two months to live a decade ago.

Since his first treatment, two other patients throughout the U.S. have begun their ARV-110 journey. Together these patients could shape how prostate cancer is treated in the future.

And, just to think, the first patient was right here in Las Vegas.

Tags: Health Care Quarterly

AnaArlene Ramirez, RN, OCN, is the research supervisor of Phase I clinical research at Comprehensive Cancer Centers.

[Patrick-Turner in reply to George71]

I sure hope this leads to more available treatment world wide. But at present all we can access is what is now available.

I might live long enough to do just that. Once something is found that does work very well, then word spreads fast demand goes high and Big Pharma give it. We might all like to lynch Big Pharma, because they tend grab too much dough, but who else is going to step up the plate to shovel coal into the engine of progress?

Patrick Turner.

[Jackpine]

I’ve had great success with LU177. Resolved my bone Mets and PSA went from 110 to 0.4. It’s slowly climbing so we’ll do a PET scan to find the still active disease.

[SeosamhM in reply to Jackpine]

Great story, Jack...the Giant Killer, apparently!

[zengirl in reply to Jackpine]

Glad to hear that. Where did you have the LU177 done?

[Jbooml]

Frustrating that things don't work out for everyone....the pursuit of our final crusade...poor choice of metaphors...i know....must include a more inclusive trial recruiting protocol advocated by patients and caregivers alike....this is total war and it needs to be treated as such. Lets put cancer in its place...extinction.