Lu PSMA treatment updates : I’ve had a... - Advanced Prostate...

Advanced Prostate Cancer

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Lu PSMA treatment updates

Javelin18 profile image

I’ve had a few requests for me to report on my Lu PSMA treatment. I was diagnosed a year ago with metastatic PCa, and my reaction to Degerelix and Lupron soon revealed that it was already castration resistant. I’ve been through most SOC treatments and started Lu-PSMA in November through the early access program. Here’s my experience so far.

My PSA was at 49 following docetaxel treatment in July, but began to rise. After starting aberaterone, it stabilized at 100 for three consecutive readings. Comparison of my Axumin and PSMA PET scans showed no discordant disease.

I got my first Lu PSMA treatment at UCLA on November 12. They hydrated me with saline IV so that I would flush the unbound Lu PSMA from my system quickly. At the end of the treatment they measured me with s as Geiger counter, which was a bit surreal.

I had inflammation of the PSMA avid sites the first few days, with the higher concentration sites having greater pain and the pain subsiding more slowly there. I was mildly to moderately fatigued for about a week. After that, pain at most of the sites was mostly gone with the exception of my right femur and hip.

Labs before and after the first treatment:

November 1: PSA 101, ALP 281, RBC 3.88

November 18: PSA 179, ALP 270, RBC 4.1

November 29: PSA 124, ALP 349, RBC 3.72

December 16: PSA 172, ALP 428, RBC 3,9

My second treatment was December 17. Same procedure snd dosage. Inflammation mainly in my right femur and hip. Fatigue had mainly subsided within 5 days. Following that treatment, my cancer pain is dramatically reduced. I still have a lot of joint stiffness, snd weakness in my legs. Pain is often completely controlled with ibuprofen and Tylenol. I’ve developed a stiff muscle in my left calf muscle and have occasional twinges of pain in my knees and coccyx.

Labs after second treatment:

January 7: PSA 167, ALP 367, RBC 3.31

I’m learning to ignore the higher PSA and ALP readings, and concentrate on the vastly improved clinical signs. My team, and Dr Aparicio told me that readings after the third treatment are more important. This makes sense to me.

Docetaxel has a half life of 12 hours, so PSA from cell death should be flushed from the system within two weeks. Lu has half life of 7 days, so is still actively killing cancer 3, weeks after treatment. After 3 treatments, much of the cancer should be dead, so PSA and ALP should drop quickly.

52 Replies

Upcoming tests are labs, including Chromogranin A, on January 20 and PSMA PET February 28

Thanks Jav,Great to hear your response and understanding of results after 3 treatments.

So treatments are about 5 weeks apart?

You mention response after 3rd, what is total?

I met with Dr Aparicio once in person, and 3 video conference calls (as we are in Florida) while applying for the SWOG 1802 Trial. I was denied entry.

She is very kind and compassionate. I feel bad for her overworked schedule. Her calls were often at 9:00pm or 8am before or after clinic.

Javelin18 profile image
Javelin18 in reply to Spyder54

I haven’t had my third treatment yet. That is scheduled for January 28. The treatments are nominally 6 weeks apart but can vary by a week either side of that.

I’m grateful for all the care providers that work to end this disease. All the ones I have met pour their energy into this, and treat each patient with compassion.

Lulu700 profile image
Lulu700 in reply to Javelin18

How true Javelin! I Too am grateful for all the compassion and human effort that has been put out there on our behalf . 👏👏

Lyubov profile image
Lyubov in reply to Javelin18

Best wishes for your upcoming treatment!

Lu177 has a radioactive half-life of 7days, but that doesn't matter because most of it is peed away before it decays. 70% of LuPSMA617 is excreted within 12 hours. It isn't actively killing cancer much after a few days.

Chromogranin A as a blood test doesn't tell you much, only as IHC on met biopsy tissue. Even that is an incomplete picture.

Javelin18 profile image
Javelin18 in reply to Tall_Allen

The only Lu PSMA that kills cancer is that which binds to PSMA on the cell surface. The 70% that is initially excreted was unbound, so was not killing cancer. I believe the bound Lu is drawn within the cells and remains there , so would still be active.

I agree that Chromogranin A is a less than ideal marker for NEPC or SCPC.

Tall_Allen profile image
Tall_Allen in reply to Javelin18

When it kills the cancer cell, it along with the cancer cell it kills are eliminated. I don't think it just stays there with a dead cell.

Javelin18 profile image
Javelin18 in reply to Tall_Allen

Sure. I think it causes double strand DNA breaks similar to external radiation, each Lu isotope only decays once, if that single decay causes a double strand break, the cell will fail mitosis and die. I think cell division occur on the order of a few days, so the cell would die, and the PSA and Lu would be excreted in a few days.

If the decay didn’t damage the DNA, the remaining Lu atoms within the cell would still decay according to the half life schedule. Eventually one those decays would lead to double strand damage and cell death. This process could stretch out over weeks.

I’m still trying to understand how many PSMA antibodies exist on each cancer cell. I know that PSMA is more highly expressed in cancer cells, but wondering what the actual count is. Since there is only one decay per Lu atom, increased number of atoms in a cell increases the damage done to the cell DNA. Each beta particle travels along one radial. To effectively kill surrounding PSMA(-) cancer, multiple emissions along multiple radials would be needed.

Tall_Allen profile image
Tall_Allen in reply to Javelin18

Lu177 emits beta particles that reach about 125 surrounding cells. Almost all of those cells die and are eliminated immediately if there are double strand breaks. The highest energy is deposited in the cell it is attached to, which has a very high likelihood of double strand breaks. And, as you point out, there are multiple sites of attachment on PSMA-avid cells, further increasing the probability of double strand breaks on that cell. If there are single strand breaks (in surrounding cells), the cells die upon mitosis (mitotic catastrophe). Very little of the Lu177PSMA617 is still around at that point. This is why they let patients go home and be around others after at most a few days.

Javelin18 profile image
Javelin18 in reply to Tall_Allen

Pardon me if I belabor the point, but I’ve had a few users say they appreciate the discussions that my posts generate. I appreciate the discussions with you, because they help me find new insight.

A beta emission will travel in a single direction, with some deflection due to interaction with electrons. It can only cause breaks along that path.

The 125 cells surround the PSMA expressing cell in 4 Pi steradians of solid angle. To kill cells at all angles requires emissions at all angles. Since each particle travels a single angle, multiple angles require multiple emissions.

This implies to me that there must be dozens of PSMA antibodies on a cancer cell. A high initial dose of LU-PSMA increases the fraction of antibodies on each cell that are bound. Other members have pointed out that they have measured their own radioactivity weeks later. All this leads me to conclude that cell death occurs over an extended period.

Tall_Allen profile image
Tall_Allen in reply to Javelin18

Yes, there are many PSMA sites on each cell. That means that the probability of a double strand break on the cell it attaches to is very high. After the cell dies, it is eliminated, along with any Lu177 that has not decayed. There is very little left in the body after a few days. Geiger counters pick up single decays, so just some residual activity does not mean there is any substantial cell killing still going on. Directions to patients is always that they are safe to go home after a few days because residual radioactivity is so low.

Seebs9 profile image
Seebs9 in reply to Javelin18

I love it when you guys talk like that...

Nalakrats profile image
Nalakrats in reply to Javelin18

I agree with you--thanks for the update. I was one of those that asked for you to update the group!


Thanks! You give A great detailed description for those of us yet to try it . I am pulling for this to work for you . 🙏🏜

Javelin18 profile image
Javelin18 in reply to Lulu700

Thanks, it seems to be working well for now. I’m taking the advice of my palliative care doctor to live in the moment and enjoy my improved quality of life. We’re planning a short camping trip for next week.

Thank you for this detailed update. This is educational for me, and I am sure it is for others. Good luck with the 3rd treatment. 👍

Javelin18 profile image
Javelin18 in reply to Skipper238

Thanks, I’m hoping to get relief from my symptoms after the third treatment. Happy to be feeling a bit more like I was before this started. I think I’m going to like 2022 a lot more than 2021

Great attitude Jav !Attitude is so important for longevity.


Javelin18 profile image
Javelin18 in reply to Spyder54

Thanks, I’m going to hijack my own post with a question. I’m wondering what the spyder refers to. Javelin18 is my fishing boat. I was wondering if yours referred to an Alfa Romeo Spider , but I don’t think they made them in 54.

No, but I love Alfa’s.I lived in Vail, CO in 72-73. Spyder (Spider);Sabich and Jean Claude Killy battled on the Pro Tour for the Championnship. I was 18-19 yrs old. We would ride the chair behind them and shadow them down Golden Peak on the Practice days. Several of my buddies said I looked like Spider (Spyder), and skiied the same style, so they gave me the nickname, Spyder. I was born in 1954, so Spyder54. Used to play a ton of Call of Duty. Played 19 against (1), me. Used Spyder54.

Ramp7 profile image
Ramp7 in reply to Spyder54

I remember Jean Claude and Spider Sabich, they brought a lot of glamor to the sport. Powder snow, here in the North East we learn to ski on ice.

Javelin18 profile image
Javelin18 in reply to Ramp7

We skied sierra cement at Mammoth. We tried to emulate The Bomber Franz Klammer and do every run like a downhill race.

MateoBeach profile image
MateoBeach in reply to Javelin18

So you were that guy! ⛷

Javelin18 profile image
Javelin18 in reply to MateoBeach

You’re thinking of my friend Steve

MateoBeach profile image
MateoBeach in reply to Javelin18

Can’t fool me. Still got my eye out for you Klammer.

timotur profile image
timotur in reply to Spyder54

Good story Spyder, the 70’s were heady days on the Colorado slopes. I worked a season up at Aspen in the days of real skiers— 4-buckle boots and 210cm skis. The seasonal workers came from all over the world and were the epitome of free spirits and healthy living. There was a local morning show in Summit county called Biff America that captured the lifestyle— wish I could find some reruns of that.

This is a very useful update 👍. What is the early access you mentioned. ?

Javelin18 profile image
Javelin18 in reply to Dermotpat

Early access is Novartis’ program to receive the treatment before FDA approval. It allows people that meet the criteria for the VISION trial to receive it. There were only a handful of centers that were setup before Novartis ended enrollment. I’m one of 60 people at UCLA in the program.

Dermotpat profile image
Dermotpat in reply to Javelin18

Thank you. My best wishes and congratulations on being accepted. Any updates are appreciated. I’m on the Arrow trial with Hoag in Irvine. I was randomized into xtandi only which I am pretty bummed with but will do the trial and see what my next steps are after finishing the trial.

Very interesting. I'm leaving this morning for my first infusion of LuPSMA617, at Dana Farber.

Javelin18 profile image
Javelin18 in reply to Ramp7

Good luck. I hope you have an even better response. I think mine is middle of the road.

Thank you for posting that Javelin. Your posts do stimulate interesting and educational information. Thank you T Allen as well.

Hello, Javelin18! I really enjoy watching your discussions with Tall_Allen! Let me insert my five cents into your dialogue and say that you will be surprised when I tell you that the decay of atoms of the isotope 177Lu continues in your body for 8 weeks, and therefore the therapeutic effect of radiation on your foci lasts the same amount! The half-life period is applied to the mass of the substance, if after six and a half days half of this mass decays, then in the next six and a half days another half of the remaining one, after another six and a half days another half, etc.! In the case of isotope therapy, we are not interested in the direction and where exactly the electrons and positrons scattered at the speed of light during the destruction of the 177Lu isotope, always in opposite directions and no further than 2 meters ... In this case, the energy of ionizing radiation during the decay of the 177Lu atom itself, which decays into 71 protons and 106 neutrons (= 177), is much more important, the energy that is released is 0.5 MeV! It is she who causes radiation damage to the surrounding cells and spreads in the form of a sphere with a radius of 2 mm. For comparison, this energy at the decay of 68Ga atoms is 0.067 MeV, and at the decay of 225Ac atom it is 6 MeV and no further than 0.4 mm.! And by the way, when 225Ac decays, positrons and electrons are not released at all - this proves once again that they have nothing to do with therapy! It is also naive to assume that only one 177Lu atom is attached to one PSMA carrier molecule - hundreds of thousands of them are attached there! On a special cyclotron, before the start of therapy, all PSMA carriers are "painted" with a certain dose of 177Lu activity.. In the case of 177Lu, the maximum isotope activity (mass of substance per unit volume) cannot exceed 10GBq! Otherwise, the biological carrier of PSMA will die before it gets its deadly cargo to the target (cells with PSMA receptors).. It does not matter how many PSMA receptors a malignant cell has - it is important that the expression of these receptors on the surface of such cells is 200 times higher than on healthy cells (cells of the lacrimal, salivary glands, adrenal glands and healthy prostate cells)! Thus, it is this moment that 200 times more carriers of deadly cargo are attached to the surface of a malignant cell and is decisive! Moreover, the death of these cells does not occur instantly, but after the accumulation of a critical dose of radiation (up to 8 weeks) and directly depends on the administered dose of 177Lu activity per injection! That's how it is about elementary particle physics! It is important to keep the T level at the castration level for the entire duration of therapy, so that there is no effect of replacing PSMA(+) cells with new PSMA(+) cells on whose surface there will be no deadly cargo! It is also very important, before starting therapy with 177Lu-PSMA, to determine using FDG the ratio of PSMA(+) and PSMA(-) cells in your tumor to assess the expected therapeutic effectiveness of this treatment! More about this in my comments under this publication: By the way, has anyone ever wondered why PET-CT is called positron tomography and why isotopes emitting only beta radiation are used in diagnostics? ))

Javelin18 profile image
Javelin18 in reply to RusLand

Your reply, and the post you linked, bring up a few questions. It seems your saying that the decay creates a spherical wave of electromagnetic radiation, rather than a Beta particle emission. This is contrary to what I have learned about Lu therapy. Can you explain that further?

The other question I have is s what is the FAPI ligand you mention in the linked post?

RusLand profile image
RusLand in reply to Javelin18

Dear, Javelin18! Radiation therapy is fundamentally different from targeted radioisotope therapy in which freely (!) decaying isotope atoms attach to your malignant cells! In the case of radiation therapy, an electromagnetic cannon (a small analog of a collider) accelerates the flow of protons or neutrons in one direction and purposefully burns out (destroys) malignant cells from outside! The FAPI ligand is a new biological carrier molecule like PSMA, which was recently discovered and which is currently in clinical trials for diagnostic purposes on PET-CT equipment using the 68Ga isotope. But in the very near future it will be used for therapeutic purposes loading with therapeutic isotopes such as 177Lu, 225Ac and others!

Having dealt with the half-life of 177Lu, expect approximately the same therapeutic efficacy when using 177Lu-PSMA under ideal conditions for such treatment! Considering that PSA in the blood serum is secretions during the metabolism of malignant cells in prostate cancer, their level in the blood should naturally decrease with the destruction of these very cells at a rate approximately two times lower, every 12 days, 4 times in a month! If this does not happen, then there may be the following reasons: 1. insufficient activity of 177Lu during administration, 2. the T level is not at the castration level and the destroyed malignant cells are replaced with new ones due to an excess of "food" for them in the form of T, 3. There are a lot of PSMA (-) in the malignant focus, which quickly replace the destroyed PSMA(+) cells! Hence my questions: 1. What was the activity of the 177Lu injected into you during the first and second courses of therapy? 2. What was your T level before the start of therapy and what is it constantly? 3. Have you had a PET-CT study with 18F - FDG to assess the expected therapeutic efficacy? For example, I will give my picture of the dynamics of PSA after each course of Lu + Ac - PSMA therapy at a constant level of T (0.087) with a slight correction for the half-life of Ac (10 days)!

Dynamics of PSA after each course by radioisotopes.

I’m not sure you understood my questions. Can you explain why you said there’s a spherical radiation wave, instead of a beta particle emission?

Also, what is the FAPI ligand you mentioned?

Javelin18 profile image
Javelin18 in reply to Javelin18

I found this article regarding FAPI as a theranostic target. I’ll have to dig into it further.

RusLand profile image
RusLand in reply to Javelin18

The answers to these questions are in my comment above, a minute after this given comment of yours! I'm not that fast, sorry!))

Javelin18 profile image
Javelin18 in reply to RusLand

Thanks, I appreciate you sending the reply above

Thank you for for sharing. My M O told me today they now have LU 177 available in Oklahoma, U S A. He is looking into me getting the treatment. From what you say, it might be a good thing.

I’d hesitate to extrapolate my experience to others, but from the indications I have now it seems to be helping. As others have pointed out, you need to compare PSMA (+) and PSMA (-) regions. It appears the best results happen there’s high PSMA expression and good overlap with cancer that doesn’t express PSMA. This allows the Lu to kill cancer in the surrounding tissue that doesn’t absorb the radiopharmacuetical.

Good progress...... and please remember "Be a thrower and not a catcher"......

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 01/12/2022 6:46 PM EST

Thank you for this update. Most of it over my head, I'll admit and will re-read again. Also thank you RusLand and Tall Allen for the additional input. May I ask as this question that occasionally accompanies discussion surrounding LU 177 and was addressed by Tall Allen in a previous post. Do you scan for PSMA non Avid (FDG Avid) cancer and if so, how do you treat alongside LU 177?

Javelin18 profile image
Javelin18 in reply to swwags

I had an Axumin PET scan,, and a PSMA PET scan. The Axumin scan shows all cancer, while the PSMA scan shows only cancer with PSMA on its surface. Lu-PSMA can only attach to cancer with PSMA on its surface. A PSMA scan and a non -PSMA scan are needed for the comparison.

If say , you had PSMA expressing cancer in your right femur (thigh bone), and cancer that didn’t express PSMA in your left femur, Lu-PSMA wouldn’t treat your left leg. This condition is referred to as discordant disease. With discordant disease , the treatment will not be of much benefit, and doctors will advise against it.

If the PSMA expressing cancer is mixed in with the non-PSMA expressing cancer, then the overshoot of the beta particles beyond the PSMA expressing cells will also kill other cancer , some of which could be a worse form of cancer. TallAllen, Rusland and I were discussing the mechanism behind that overshoot effect.

There is another related discussion as to what other non -PSMA scan is the right one to use , but that’s a whole other discussion.

swwags profile image
swwags in reply to Javelin18

much appreciated

RusLand profile image
RusLand in reply to Javelin18

Dear,Javelin18! I don't think that our discussions under your post somehow hurt your ego.. I wouldn't want that! The truth is always somewhere in the middle and that's how we learn about something new and progressive that will help us or follow us to defeat this insidious disease that kissed us ..)) Maybe my browser translator slightly distorts my thoughts, but I am grateful to everyone who shares their stories of victories and failures. Because the mistakes of those ahead warn those who follow not to repeat them! I don't know if you've read the article that Tall_Allen posted: But in this article, in addition to mentioning the importance of studies on PET-CT with FDG before radioisotope therapy, I found information that the presence of disorders in the BRCA 1 and 2 genes also affect the results of such treatment in the direction of its effectiveness. And that simultaneous administration of Olaparib for such patients with radioisotope therapy with a PSMA ligand can also increase the effectiveness of such therapy. This is a very interesting thought and I decided to do a BRCA 1/2 mutation test for my malignant cells. I will also ask all familiar patients who have been treated with the help of the PSMA ligand to do such a test.. I will share the results with you and with my doctor - it's very interesting!

Javelin18 profile image
Javelin18 in reply to RusLand

Don’t worry about hurting my ego. I think we should be able to disagree on our understanding of the disease and treatments without having our feelings hurt.

I was tested and don’t have any known mutations.

Fascinating reading, always learning. One day after my first infusion, feel fine. A little tingly in the groin where metastases have been identified. I traveled to Dana Farber, about 2.5 hours drive. This is a phase 3 trial. Turns out that I am the first patient to receive LuPSMA617 in their trial. Four before me were chosen to advance to Xtandi first with the ability to cross over to LuPSMA617 when effectiveness diminishes. A lot of fan fair, the Team at Dana Farber seemed very excited. To gain acceptance into the trial tests was pretty extensive. Review of original pathology report and the sample. Blood work, Bone scan, cat scan, MRI, Pet PSMA scan. After this I had to under go 5 radiation treatments on my spine, L4/5. The sponsor seems to be the one making all the decisions for acceptance. I think I'm correct in saying that 90% of the cancer needed to express PSMA to receive LuPSMA617. It was also mentioned that the delivery method has changed over time. The infusion took about 30 minutes. It is very slowly administered via a port. This slow release has reduced unwanted early side effects such as vomiting and nausea. Everything went very smooth.

Glad to hear your first treatment went well. My infusions were slow also. I’m interested to hear how your PSA is effected over the next few Erik’s.

They gave me a saline iv for about half an hour, then put a couple iv lines into the shielded container to flush the drug out of the container and into my arm. They also gave me zofran at the beginning of the procedure.

Other than lighting up a Geiger counter, and having to pee, it didn’t notice sny effects during the procedure.

The Geiger counter was a hoot. They didn't have to be very close to me. It was not a subtle announcement. Under different circumstances, it could have been funny.

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