LU177 3rd dose

[Zhyravlik]

Hi! Well finaly my dad got in to the Lu177 clinical trials in Moscow. 1st round was 23 of Feb, then 2nd in 24 of March. Both time he got 9Gb of Lu 177. PSA before 1st injection was 112 and before 2nd 63. In this clinical trial they are using smal dosage 3,5 Gb but with short gap 2-4 weeks. But we decided to buy additional dosage and he got 9 Gbk. Both time he didn`t have any side effects and improved quality of time.

But in 2nd Lu177 mix doctors added Samarium-153 200Mbk. And actually there was small side effect like "sand in the eyes".

Actually we were prettly glad with this outcome. But then suddenly i got call from hospital and they said we should came for next round 6 of April. Therefore it will be just 2 weeks gap between. And reason for this was - father tolerate treatment very well and there probably will be shortage of Lu177 soon. If we will refuse this time, there are not sure when next time they can offer. There actually will be shortage of everything now, especially of drugs

So we stuck with few options:

1. skip for now, take time to restore blood (it`s not bad actually) and hope thet next month there still be available Lu 177

2. go and take 3rd round of 9Gbk and hope that there will be not too much of radiation

3. go bu reduce dose to standar free of charge 3,5 Gbk???

[NotAlwaysSunshine]

Curious - can you go to Germany for the rest of the treatment?

[Zhyravlik in reply to NotAlwaysSunshine]

no more traveling for russians well we still can go to Turkey, but everything is 3 time more expensive for us now

[NickJoy]

I don't know if this helps at all but my husband's radiotherapist from Finland mentioned that they were experiencing difficulties obtaining Lu also - so although they are on your door step it looks like it might be a global thing as they have been using it for several years so should be familiar with obtaining it I am guessing.

[NickJoy in reply to NickJoy]

Maybe Rusland could advise as he is close and knowledgeable?

[Zhyravlik in reply to NickJoy]

I did actually asked for his advice, and he is agains small gaps between tratmens. I guess we will try 3rd round with faith in our doctors words. We pay additional money for "personal treatment plan", so lets hope it will work out. As doctors said they have manage to calculate very well dosage and time for patients. And have a very good rate of good outcomes with this Lu treatments.

[GP24 in reply to Zhyravlik]

I agree with Rusland. The Lu177 will reduce the tumor but not cure you. You might as well get the third cycle any time later this year. I try to make gaps of two years between cycles. But I am still hormone-sensitive.

[Javelin18]

This is a difficult decision. It is a guess as to if the drug will be available, what side effects might be and whether the smaller dose would be effective.

I think the safer approach is to assume that the drug won't be available , and get the next treatment while you can. He has tolerated treatment well, so the high dose might not have bad side effects again, but the treatment is much closer, and the last treatment will still be in his system. On the other hand, his cancer load should be lower so the smaller dose might still be effective.

Unfortunately, with advanced cancer we're always making treatment decisions without enough information to choose the best option. All we can do is weigh the different options, get advice from doctors and other patients then choose.

[Zhyravlik in reply to Javelin18]

I guess you are right, we should take available treatment now. Still we have Enza and Cabazitaxcel treatments left, but it`s look like Russia will be out of Enza soon. Especially free of charge. They have russian version of Abi, but i guess don`t have any Enzalutamide yet. I hope this situation will rosolve soon, but it`s look like we should prepare for worse in every aspect and take this treatment while planes still flying :)I think we will try 3rd round with faith in our doctors words. We pay additional money for "personal treatment plan", so lets hope it will work out. As doctors said they have manage to calculate very well dosage and time for patients. And have a very good rate of good outcomes with this Lu treatments.

[NickJoy]

I wish your Daddy the very best with the treatment.

[Zhyravlik in reply to NickJoy]

thank you 🙏

[RusLand]

Katya, hello! With your permission, I will answer here and in English ..)) You addressed your questions to me on Whatsapp, but I think that some participants may also be interested. And so, your dad has already received two courses of therapy with an interval of a month with an activity of 9 GBq.. Russian doctors have moved away from standard protocols when 7.4 GBq of 177Lu activity is administered at intervals of 6-8 weeks. This time is given in order to restore the hematopoietic functions of the bone marrow and excretory functions of the kidneys, through which residual radiation is mainly excreted from the body. It is also necessary to understand that the half-life of isotopes is the time during which only half of the activity decays! In other words, 6 days after the administration of the drug, another 4.5 GB of activity will be present in your dad's body, 2.25GBq of activity after another 6 days, etc. Thus, with the activity of 177Lu at 7.4 GBq, the minimum break between injections should be at least 6 weeks, more is possible, less is impossible due to the great threat to the bone marrow and impaired kidney function! Your dad was injected with 9 GBc activity - this means that the interval between injections should be at least 8 weeks! You write that in the second year, without your knowledge, 200 MBq of 153Sm was added to 9 GBq of 177Lu activity.. The Samarium isotope accumulates selectively only in the foci of bone resorption, including bone mts.. But it also accumulates in all areas of bone degeneration and especially in the spine in close proximity to the bone marrow! With the combined introduction of isotopes, for example 177Lu + 225Ac in the centers of excellence, the break between courses is 8-12 weeks! It is believed that in a maximum of 12 weeks, any normal body should recover completely if there were no serious problems with the bone marrow and kidneys before the start of treatment.. Your dad's hemoglobin level was initially lowered, after the first course it also remained lowered.. I have seen your description of PET-CT with 18F-FDG and have also seen pictures with 177Lu distribution SPECT.. The main lesions of your dad are located in the spine and the 177Lu osnavnaya part accumulates there.. At the same time, the SUVmax in all affected departments did not exceed 6 units before the start of treatment.. Believe me, this is not so much and it means that there are not so many PSMA(-)/FDG(+) cells in the foci of your dad! It would be nice to compare it with PSMA(+), but you say that PET-CT with 68Ga-PSMA was not even performed at this center..?! For me personally, this is very strange!!! It turns out that specific radiologists inject radiation blindly just for luck...((Let me remind you that it is in the spine that our red bone marrow is located, which produces red blood cells that carry hemoglobin! I am not a doctor and for this reason I have no right to give you medical recommendations! But I am a patient myself, who has completed 4 courses of 177Lu+225Ac-PSMA therapy and plunged into this topic with my head, who has access to medical documents to more than 20 patients whom I helped to undergo this treatment at the center of excellence in Baku, who is in constant contact between these patients and the head of this center and has accumulated certain statistics on according to the data I have.. Based on the above, I can say what I would do personally in this case.. Considering the fact that during the second year you underwent combination therapy of 177Lu + 153Sm in high doses of activity of both isotopes (for understanding the maximum dose of activity during coination is 5 GBq Lu + 5 MBq Ac) I would take a break in 2-3 months! I would continue to keep T on the castration level and monitor the readings of RBC, HGB(Hb), HCT - this is red, bone marrow! And Creatinine, Urea are the kidneys! During this period, I would hand over the biomaterial you have for the determination of mutations in the BRCA1/2 genes. Judging by the results of PET-CT with 18F-FDG, your dad developed necrosis of the lower jaw, apparently due to taking drugs against bone resorption.. For this reason, it is necessary to contact an oncologist-stamotologist and solve this particular problem in these 2-3 months! If you tell the participants about the cause of your dad's mandibular necrosis in a separate post, then I think you will do a good service to the rest of our community members who take Zolendronic acid and Xgeva.. Yes, and in conclusion, 177Lu of Russian production is used in Russia, and I don't think there will be problems with it! Here is my humble opinion in response to your questions..))

[GP24 in reply to RusLand]

Hi Rusland,

you may be interested in this Webinar: warmth.org/index.php?option... Prof. Emmett presents the Lu177 trials currently recruiting in Australia and Prof. Sator presents details of the VISION trial. He also mentions that he currently thinks one should use higher doses per cycle, based on this trial:

urotoday.com/video-lectures...

gp

[Zhyravlik in reply to GP24]

Thank you very much for this links. Very informative. And in video there is one patient with 2 weeks gap and 9 Gb dosage and he is quite well. Hb improved from 80 to 124 and PSA drop from 90 to 10. So it is worth to try

[RusLand in reply to GP24]

Hi! Yes, yes, I don't mind a high dose of Lutetium isotope activity! The maximum dose for it in the centers of excellence is 10 GBq and I believe that with multiple mts in the bones (more than three) it's absolutely necessary! I am against the introduction of high doses of 20 GBq of Lutetium isotopes in short periods of time! It is necessary to understand that the destructive effect of radiation is cumulative! The salivary and lacrimal glands are the first to suffer due to the physiological properties of accumulation! Bone marrow and kidneys are the number two goal! In my experience of treating patients at the center in Baku, three patients have already died due to kidney failure..(( Thus, before starting treatment with the PSMA-617 ligand, it is necessary to conduct a comprehensive examination of the patient in order to assess the expected therapeutic effectiveness of the upcoming treatment with radioisotopes! I'm only talking about this and this is just my subjective opinion!

[GP24 in reply to RusLand]

In many cases Lu177 is used after all conventional treatments have failed. In this situation Prof. Emmett mentioned that the patients have a limited remaining lifespan and therefore it is more important to treat the tumor effectively than to worry about side effects. Therefore she would apply higher doses than 7.4 GBq.

However, if you e.g. just got castrate-resistant and want to combine your Olaparib therapy with Lu177 radiation, I think you should use doses which do not cause significant side effects.

I also agree one should apply only one high dose cycle and then monitor the results with imaging before deciding for a second cycle.

[RusLand in reply to GP24]

Perhaps I misrepresented my thought..?! There are patients whose PSMA(-) exceeds PSMA(+) cells in this case, treatment with the PSMA-617 ligand is hopeless! In some cases, this treatment may aggravate the patient's condition due to the fact that the destroyed PSMA(+) cells will be quickly replaced by PSMA(-) cells and PSA will grow even faster.. In each case, it is necessary to examine everything very carefully before starting treatment! This is my opinion!

[GP24 in reply to RusLand]

.. due to the fact that the destroyed PSMA(+) cells will be quickly replaced by PSMA(-) cells and PSA will grow even faster.. I think this is no fact, it is your opinion. I am not sure that the PSMA positive cells will be replaced with PSMA negative cells, it could be PSMA positive cells as well. I also do not think that PSMA negative cells grow faster than PSMA positive cells. This is my opinion.

It depends if the patient is in a final situation. In that case he may have many PSMA negative cells which can be detected with an FDG PET/CT. If there are more PSMA negative cells than PSMA positive cells, the Lu177 treatment will not be effective.

[RusLand in reply to GP24]

I absolutely agree with you! In the centers of excellence, that is why it is recommended to conduct two PET-CT studies, one with 68Ga-PSMA-11, the second with 18F-FDG, and I write a lot about this, that it is mandatory! Keeping T at the castration level is one of the reasons that new PSMA(+) cells cannot replace PSMA(+) cells destroyed by radiation! In cases where, according to the results of two PET-CT studies, it is found that FDG(+)/PSMA(-) cells are more than 50% than PSMA(+), then the radiologist recommends not to conduct therapy with the PSMA-617 ligand! The fact that in this case, immediately after the first course, a sharp increase in PSA begins is also a fact! Just like I asked all 20 patients treated with PSMA to take tests for mutations to the BRCA1 and BRCA2 genes.. It turned out that the treatment with radioisotopes is most effective in those patients who had mutations in these genes! Yes, it all requires a lot of study! Here TA posted a good link to what exactly you need to pay attention to before starting treatment with the PSMA-617 ligand: prostatecancer.news/2019/12...

[GP24 in reply to RusLand]

"It turned out that the treatment with radioisotopes is most effective in those patients who had mutations in these genes!" Could be that these patients got Olaparib? Here is a trial testing the combination of Lu177 and Olaparib.

twitter.com/hashtag/LuPARP?...

clinicaltrials.gov/ct2/show...

Prof. Emmett mentions this trial in the webinar and says, the understanding is that Lu177 causes single-strand DNA defects which the tumor cell can fix. Olaparib causes these single-strand DNA defects to become double-strand defects which the cell cannot fix and thus dies.

SSD (single-strand DNA breaks) and DSD (double-strand DNA breaks)

[RusLand]

Attention! The effect of radioresistance has not been canceled.. A sharp decrease in the activity of the Lutetium isotope from 9 to 3.6 GBq by almost three times can make treatment with this isotope useless in the future! And at the same time, repeated administration of a high dose of Lutetium activity in the interval of 3 weeks can lead to irreversible consequences for the bone marrow and kidneys! You need to get a professional second opinion from radiologists who have been working with 177Lu-PSMA-617 for more than one year! There is very little clinical experience in the center where you are currently undergoing your treatment, and you have only one dad.. Think about it!

[RusLand]

Katya, one thought does not leave me.. I have mailed you two packages of the original Zytiga abiraterone and I know that you have received them.. Please analyze when you started taking this drug, what was your break in taking abiraterone? What was the dynamics of the PSA in the intervals between abiraterone doses? I am concerned that the effect of resuming abiraterone intake could overlap with the effect of radioisotope therapy and distort the final results..?! Abiraterone is also able to reduce PSA levels by more than 50%.. This fact also needs to be analyzed!

[Zhyravlik in reply to RusLand]

Thank you for your concern. Yes fater start to take Abi after 1 month breake. Maybe good result of treatments combined together. But after 1 year of Zytinga PSA was rising. We will consult our doctor before treatment. When we will have all blood works on our hands