Why I Choose an Unproven Treatment

[MateoBeach]

It is a rainy stormy day in Perth, Western Australia, called the "most remote city in the world". I arrived here yesterday with more than 30 hours of travel from Oregon USA. Tomorrow I will get my first infusion of Lutetium 177-PSMA (mAb)-J591. An experimental and unproven new form of radioactive ligand therapy for advanced prostate cancer. The question is: "Why?"

Why am I doing this? It is not SOC. There is not even a proof of concept for it. It is an outgrowth or extension just hoping to build upon the limited success of Lu-PSMA-617 used in the VISION trial and recently approved for mCRPC under the branded name Pluvicto.

There is a Randomized Phase III Clinical Trial (RCT) for this new drug and treatment approach for metastatic CRPC that is now recruiting. But I do not qualify for that trial called the PROSTACT trial. I am "not advanced enough: That trial uses this same drug, variously called 177Lu-DOTA-rosopatamab, AKA Lu-DOTA-TLX591 (by Telix Pharmaceuticals), or as I know it Lu-PSMA-J591. It uses a humanized monoclonal antibody to very strongly bind to the PSMA protein on the PC cancer calls' surface. Much more strongly held than the PSMA-617 small molecule "ligand" used in the VISION trial (now Pluvicto) and has been in extensive use in other countries for several years.

The PROSTACT Trial is being led by chief investigator, Dr. Nat Lenzo, who is also the one advising, treating and monitoring me in my experimental treatment. The trial, which is now enrolling patients, is for those with mCRPC who are progressing, with a PSA >2.0 after previous ADT plus at least 12 weeks of an Advanced Androgen Receptor drug, and at least one series of a taxane chemotherapy. And also must have at least one metastatic site with strong PSMA avidity (SUVmax) on a PSMA PET scan. In other words for highly advanced, highly pre-treated stage 4 prostate cancer. Then they will be randomized 2:1 to receive 2 doses of the treatment drug (45 mCi equal to 2.8 GBq of radiation dosage) given two weeks apart. Vs. Placebo in an open-label protocol.

177Lu-DOTA-rosopatamab With Best Standard of Care (SoC) for

the Second Line of Treatment for Metastatic Castrate-resistant

Prostate Cancer, Which Expresses PSMA (PROSTACT)

clinicaltrials.gov/ct2/show...

I do not meet the entry requirements for this study in that I am metastatic hormone-sensitive PC; Have not been on an AAR drug; And I have no PSMA avid sites left after SBRT of the only 2 visible nodes a month ago. And my PSA remains < 0.20. The risks of this treatment are substantial, with no proven benefits. Because theTLX591 (rosopatamab) monoclonal antibody binds so strongly to the PSMA protein it is not eliminated from the circulation nearly as fast. It goes everywhere and for much longer than Pluvicto. This causes much more bone marrow toxicity, certainly in the short term and possibly for the long term. Anemia is expected, sometimes severe, with 25% of patients requiring transfusions. Thrombocytopenia can also be severe with 10% requiring platelet transfusions. Fortunately, renal toxicity is absent since it is not excreted by the kidneys but rather the liver. But that is why it stays in the system so much longer and releases more radiation in the body rather than being rapidly excreted.

So the question I want to address now is: "Why?" Why am I doing this tomorrow morning at 9 AM? In order to answer that I must look at who I am as a person, and who I have always been. How do I live and have I lived my whole life? I embrace life and have always embraced challenges and sought out adventures that stretch me to my limits. Because I love life. Because I want to know and to live the fullness of my life- Of all that is possible. Of myriad dimensions and arenas of action, of knowledge, of being, and of love. I want to seek and to know THAT love that holds us all and sustains life. A life of fullness and celebration in every stage of life.

So that includes now. Even as an "old man" in body with cancer that cannot be cured that has diminished my capacities along with the changes of aging. But I will not be stopped from living as strongly and robustly and intensely as I am able. I fight against frailty and infirmity. And I fight against my cancer (that has also been my teacher).

So this experimental, a non SOC, non tested treatment, which is a new and different application of targeted radio-isotope treatment to earlier stage cancer, as I am now. Hormone-sensitive. oligometastatic, low tumor burden, no remaining PSMA avidity, with low PSA < 0.20. Yet still with metastatic prostate cancer). And I'm not on long-term ADT, but rather using high-dose cyclic testosterone treatment, which is also unproven and not SOC.

This is part of a two component treatment plan: First, treat the PSMA avid metastatic sites with SBRT. This was done last month.Then one month later do the two radio-ligand treatments with Lu-PSMA-TLX591.

This is what adventurers do. This is what explorers do, climbers do, astronauts do. This is what I choose to do because that is who I am. And how I (still) want to live for all of my days, be they few or many. So tomorrow May 13, 2022 here in Perth West Australia we proceed. The Great Adventure continues! - MateoBeach -Paul

[jdm3]

Good for you thinking outside SOC and being adventurous. Thanks for the narrative and good luck. All the best for a successful treatment and we look forward to periodic updates.

[cujoe]

Paul the Pioneer,

As a personal account of one's reason for choosing a treatment, your post is a remarkable testament. All who read it will hopefully feel as privileged as I do in having the opportunity to do so. It is a well-crafted summary of your disease state and your reasons for undertaking what can only be described as an exploratory treatment - with at least some degree of unpredictable results and/or unknown side effects. More than that, it is a statement of purpose worth framing for future reference. You should know by now that there are many of your PCa brothers (and supporting sisters+) who have and will continue to watch very closely your treatment progression. May it prove as effective as you and your AU doctors expect and, in doing so, crack the door open to a possible new treatment option that many in our community may someday need. Some will not be able to wait years for the trials and FDA approvals required for such a treatment to finally reach the clinic.

As mentioned in a reply to one of npfisherman's recent posts, I just finished reading the 2013 book by Clifton Leaf, "The Truth In Small Doses: Why We're Losing the War on Cancer - and How to Win It". In it Leaf profiles how the institutionalization of our clinical trial process and research funding has gradually resulted in the elimination of the sort of cutting edge experimentation that once lead to "break-through" drugs and treatments. What we now get instead, in the author's words is: "More funding, Yes - but few 'new doors' are being opened". This has fostered a culture where the same select group of institutions get the lion's share of the funding year after year, resulting in look-a-like drugs that plow the same ground - and few, if any, of the truly revolutionary treatments that were routine in the early days of cancer research. Leaf's book left me with the realization that the true pioneers in PCa treatment are no longer located in Big Pharma or the major cancer research centers, but with courageous patients like you.

In counting myself among the many who look at SOC as a bit of a fool's errand, I will continue to explore options that offer me better QOL while still extending my life. I've adopted a modified form of a statement I saw in a reply at APC. My rewording is: "I'm interested in adding life to my years, rather than (lesser QOL) years to my life." While that is not a motto all PCa patients can embrace, it does seem to be in the spirit of your post and I celebrate you for that. I've been bedside for the last breath of both parents and two older siblings from cancer and no longer fear the C-word. I will put QOL above longevity, especially if it affords me more opportunity to seek and know that same bonding love you speak of. I've found some of it in the individuals I have come to know via HU - and there is much more of it waiting for both of us yet to find. "Seek and ye shall" find is an adage worth pursuing at any age. At that of most PCa patients, it just becomes more so.

I'm sure I speak for all who read your post, when I say that we wish you only the best outcome. Your expected pleasant visit with the superb HU-connections who will entertain you in Sydney is definitely your trip's extraordinaire bonus package. The Marnie & Ron clan are excited for your visit and I fully expect they will individually and collectively be the perfect hosts for your time there. Live it and Love it! (Maybe you'll even get to laugh it up with the Kookaburras?)

Safe travels in country and on your return. And throughout the entire journey, Stay/Be Very Well,

Ciao - The Unleashed K9 Terror

PS Thanks, Paul, for also posting this here at FPC so at least two of us ostracized regulars here can reply.

[MateoBeach in reply to cujoe]

Terrifying One: thank you for your kind words. ( I had a previous K9 that was named Kojo and many people misheard and thought it was Cujoe. Kojo is a Ghanaian name for boys who are born on a Tuesday.)Anyway, much of what I wanted to reflect concerning your comments I just wrote to NPFisherman in a reply below, so I won’t repeat it now. But I thank you for the lead on the Truth in Small Doses book that I am reading now. There is so much insight also to be gained in Emperor of all Maladies. The story of how Gleevec came to be approved and marketed is a thriller. Actually I have a friend in Oregon who was dying from end stage leukemia. Then he became the last patient to be randomized into the trial. He is still living strongly to this day! Against all odds and obstacles, progress can happen.

Thanks for all you and Fish do to support Marnie and Ron and so many others. MateoBeach. ( Mateo is the name of my current dog.)

[cujoe in reply to MateoBeach]

Paul: I just checked and I was born on a Sunday, so even tho' I am a boy (at heart) with an old(er) man's body and ADT now slowly stealing away the testosterone that every male wants and needs to feel "normal", I cannot rightly claim the Kojo name equivalent. That's really too bad, as it would have allowed me to evade the Stephen King source for my moniker - affectionately given to me by a co-worker back when the book with similar name (sans the 'e') was still present in the common culture. The "terror" qualifier was added after j-o-h-n joked (as he is prone to occasionally do) that the name Cujoe also referred to a "sometimes K9 Terror in a movie by the same name".. (or something to that effect.) So, you see the name Cujoe, like your Kojo, also has a long and colorful history to share.

I think maybe you are scheduled for a treatment about now? May it go well and you have zero lingering side effects. Dr. K9 orders, of course. Stay Safe/BeWell, Ciao - K9

[NPfisherman]

I don't think there is anything I can add to what our K9 Wonder said so eloquently... I have encouraged others to participate in clinical trials and have participated in a clinical trial myself...

I congratulate you on your n=1 experiment and wish you all the best of luck on your journey, while I have my own n=1 experiment. I might reconsider using Veyonda if I were you for the potential abscopal effect-see below:

noxopharm.com/site/our-scie...

But that is up to you, of course. While it has not been tested with Lu-177, I would think there is some potential there since it is a radiation treatment and probably a longer acting one...Currently, I am looking at natural radiosensitizers that may have an abscopal effect to produce my own suppositories prior to SBRT ande use them. I believe this is another way knowledge develops on these forums. People do an n=1 and report, so please let us know how it goes...

Enjoy your time down under with Ron and Marnie. I hope to do the journey at some point post retirement. Travel well and Be safe...

Fish

[MateoBeach in reply to NPfisherman]

Thank you for those kind words, Fish. I only recently learned about the alternative channel in FPC. Uncensored! 👏🏻👏🏻 So posted to both.I have been slowly refining my thinking on SOC and plan a post soon that I will title “The Raggedy Edges of the Standard of Care”. About how it is a very slowly evolving process built one small brick at a time. And what we do not know always expands even as we add incremental knowledge and refine or throw out misunderstandings of the past. That book Truth in Small Doses, I have just started reading explains the problem. But I don’t want to discourage other APC men from distrusting the whole system altogether. So I am going slowly with that. Not that I will have the last word on it anyway!

Visiting GenesisC in Perth today was amazing they have a beautiful huge facility, brand new, here in Perth. It was a very nice experience altogether.

I did have a chance to ask Dr Nat about Veyonda and where they were with that. For a couple of years Noxopharm was very generous with them and were supplying it at no charge.but they are a small company and can no longer afford to do that. They were hoping that a Big Pharm company like Novartis would come buy them and take over Veyonda, especially for combined treatments with their immune drugs. But Noxopharm started exploring other modes of actions and applications for it, including for COVID. This, Nat feels, scared off the big players.

In the meantime, they had treated thirty something PC patients along with PC. They did not feel that they were getting the astounding results that were reported in early phase trials. Rather just a modest improvement perhaps in those achieving 50% PSA reductions. So perhaps an incremental advantage to adding it, but not a game changer.

I also am in including natural radio-sensitizers with this current treatment. Especially since I was on some already. Notably Quercetin, Curcumin, and Metformin. Forgot to bring a bottle of Resveratrol with me, but have been on the fence about that one anyway.

So looking forward to being with the Marnie and Ron clan after this weekend in person. Kind regards and appreciation, MB

[NPfisherman in reply to MateoBeach]

You are most welcome and most welcome at the only "uncensored" PC forum on HU... The K9 Sometimes Terror and I are the banished, but undaunted. We tend to have a more open minded approach concerning non SOC routes and ideas, n=1, etc.. and I look forward to your posting on "The Raggedy Edges of SOC", because indeed...it is raggedy and leaves a lot to be desired...

As far as Veyonda goes, this article just showed up in "Practice Update" so I wanted to share it with you regarding safety and some results:

practiceupdate.com/c/135002...

Glad you are enjoying your time there and as before...best of luck...

Fish

[MateoBeach in reply to NPfisherman]

In addition to the personal comments from Nat Lenzo today in response to my questions about Lu177 plus Veyonda. The results published recently on the LuPIN trial are along the same lines. In mCRPC previously mostly heavily treated (=advanced disease) their small trial showed a 60% response with PSA drops of 50% that persisted for median 7.5 months befoe PSA progression. Median survival 19.5 months. No placebo controls. her is the link:

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

[NPfisherman in reply to MateoBeach]

OK....it is the same info from Practice Update....sorry I didn't see this post before I sent my response...

Fish

[NPfisherman]

Thanks for posting it here... I am so restricted on APC that I can not even "like" a post there. There is probably something dangerous in my liking a post...go figure... I am glad I can give you best wishes and a thumbs up here.... Again, good luck...

Take care,

Fish

[cujoe in reply to NPfisherman]

According to Admin there, the 'liking' was deleted in a new "software revision" about six months ago. I also note that we no longer have access to the 'Members' listing there. Wouldn't want either of us having direct contact with any members and possibly corrupting them, now would we? (Never mind the fact that one of the principle reason I joined that forum was to share my AUS experience with fellow patients in need of help with serious incontinence.)

I guess that's why I sometimes like to refer to you as Dangerous Dave and frequently use my K9 Terror moniker. We have nothing to fear, young man, except fear itself. Or at least something to that effect . . .

So, as we both now have to struggle to carry on with our lives as outcasts, Peace on ya', Bro'. Divided we fall! United we stand - very tall! Ciao - K9 Terror

[NPfisherman in reply to cujoe]

K9 Terror,

Thanks for the kind words and information...Yes, God forbid that we should be able to "like" a post and that HU wants to make sure we can not see "the list"... Damnation, I am Dangerous... and you are a Terror in this dog eat dog world of PCa forums... Whodda thunk it???

Now I saw somewhere that an Administrator felt threatened by a forum member on another locale... and they think we are a danger?? We are like Ding Dongs... A hard exterior with a creamy interior that is easy to digest..very satisfying....and on that note, let us play ode to the Ding Dongs on Friday with some music from "Animal House"...

youtube.com/watch?v=gYwqVEE...(Not working as expected?)

I think maybe I spent too much time at work today... Time to go find some bourbon and Fresca and embrace the weekend....LOL... sound advice for all...

Be safe and Be well...

The Ever Dangerous and Somewhat Crazy Dave

[Spyder54]

Paul, any updates you can share? How are you holding up? Able to enjoy Western Australia?Thanks,

Mike