This is a nice follow-up to the PeterMac podcast Marnie posted yesterday. It also helps to confirm Don Pescado's claim that "the Science is Coming".
In this Lancet comment article by Louise Kostos & Declan Murphy, both at PeterMac in AU, they update the current treatment options/recommendations for metastatic, hormone-sensitive PCa in light of the Phase III results from the CHART trial comparing ADT plus the new ARI agent rezvilutamide vs ADT plus bicalutamide - in this case for patients with high-volume, metastatic, hormone-sensitive disease.
Once again, the people at PeterMac emphasize the lack of the universal application of combination therapy (ADT + ARIs) for many PCa patients. They also restate the clear evidence for the superiority of PSMA-PET in the initial determination of disease volume and restaging those initially staged with conventional bone/CT scans.
The Lancet PeterMac Comment article is here:
Treatment options for metastatic hormone-sensitive prostate cancer - The Lancet Oncology - Comment by Louise Kostos & Declan G Murphy, Published: September 05, 2022
A MedPage Today article on the trial results here:
Rezvilutamide Bests Bicalutamide in Metastatic Prostate Cancer — Combined with ADT, the androgen-receptor inhibitor significantly improved OS, radiographic PFS - by Mike Bassett, Staff Writer, MedPage Today, September 7, 2022
Rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy in patients with high-volume, metastatic, hormone-sensitive prostate cancer (CHART): a randomised, open-label, phase 3 trial - The Lancet Oncology, Published: September 05, 2022
Preaching to the choir...or at least, a fisherman on the water... The question that I have regarding Rezvilutamide is not how it stacks up againt the oldest lutamide, but rather against the others...enza, apa, and daro... if efficacy is similar, but with lesser side effects and cheaper....then welcome Rezvilutamide... quite honestly though, this is a sideways move...
We need new classes of drugs... we do have Veru-111( a microtubulin inhibitor) in Phase 3 --VERACITY trial, with an estimated completion date of May 2024, but a bromodomain inhibitor seems 5 years away most likely or longer... Osteodex ( a targeting drug for bony metastases) is ready for Phase 3, but it's show me the money for the study... (Fudge !!!) The Science is Coming, but dang it, Science.....Put the pedal to the metal !!!
I do wonder if we got all urologists to use an ARPI with ADT would the survival rate change to 60% from 32% or so... Folks, if you are new here and only on ADT, then get your rear to a Center of Excellence and get on an ARPI with that ADT ASAP !!
As for the new scans, well those have resulted in a crucial change in prostate cancer treatment... so much that I would say it is.... "The World Turned Upside Down..."
An ARPI drug is an Androgen Receptor Pathway Inhibitor... This would be drugs like abiraterone, enzalutamide, apalutamide, or darolutamide, or this new drug rezvilutamide.
Your urologist is 5 years behind the time and that does not bode well for your survival... Let us know where you are and we can help you find a Center of Excellence, or if you know of one, then get there... No one should be started on ADT monotherapy anymore... Mother of Pearl....what incompetence !!!!
If you stuck with your urologist then you will have to drive the ship since you had to insist on abiraterone, but maybe you are at a Center of Excellence now...
At any rate... wise decision on your part to get on abi... I took a quick look at your profile, and you seem to be oligometastatic (2 mets)... Are you considering SBRT and if not, then why not?? There is a lot of misinformation on that issue...
Agree across the board with your comments re: ARPIs and on Sartor. As i commented to jdm3 who is looking for a new MO (as his current one is leaving D-F) ~ "All things being equal, Sartor would be my hands down #1 choice for a MO in US". He embraces SOC, as well as BAT, etc. - evidence that he is apparently not afraid to think outside the box when it is in the patient's best interest.
IMO, that is the sort of MO "partner" we all need in directing our individual care and treatment progams.
The Science is Coming, and the treatment paradigm is evolving rapidly. Finding an MO that is following the evolution and adapting to it rapidly is key. My MO at Cleveland Clinic started me on Lupron and Abiraterone at the same time. He was not in agreement with my choice to have SBRT in 2018. He arranged for my Pylarify scan this time and asked me later if I had arranged my SBRT He is adaptable. It's what we all need...
tell him/her you are going to get Abi+p or you are going to get a lawyer. Those urologists that don’t prescribe AARIs are probably not knowledgeable about monitoring and managing them. You need experience as they are more complex than a shot of Lupron. (So get a new MO). Go Fish!
It's great Ross on two counts...one that you're across the data that clearly indicates that that mono therapy is a fast road to castrate resistance for most men...and secondly that you've found a new Brisbane MO who is prepared to listen to you and prescribe Abi in spite of it not being SOC.
No doubt the trial data will finally sift through and more doctors here will be willing to prescribe off label for those who can afford the cost. There's no doubt both Abi and Enza will eventually be covered by PBS. In the meanwhile those, like you, who want to follow the clear data that adding one or other drug to ADT early is the best way to go, will just keep having to fork out close to $A4k a month.
Just a shame that it costs so much when it's so b______y obvious that eventually it will be approved for those who are castrate sensitive. What you can almost bet your money on....well whatever is left over after forking out now for Abi...is that when they are approved in the US...it will still take ages for the pharmaceutical company to start to look at the Australian market...as has been the pattern with most things... they'll go where the big market is first.
The reassurance for you is that most urologists and MO's who really are across the trials and data express disbelief that men are still being prescribed ADT alone.
Enjoy the day ahead...we've had a few fine days in a row which is a novelty and a nice sunny day ahead for you too. Marnie.
Marnie is right in her outrage of course. In the meantime perhaps you can order generic abiraterone from India and take the 250 mg/day dose with fatty breakfast ( why do you call it down under). And cost may be acceptable. Gotta live right now. MB
Yes Paul, I find it astounding and definitely outrageous that in a country where some of the leading research in PC is conducted and globally acknowledged, that the SOC is basic ADT until that fails. If you are happy to follow SOC... and happen to understand that the evidence supports a contrary path - that is to add a second line... - you'd best be able to - first find a MO who is conductive to accommodating your request and secondly be in a position to pay big time.
Now as to the 'down under' reference... you'd best listen to Men at Work's tune...gross video link which I refuse to send!!
Trust you had very happy travels and engaging conversations...next time...M
good clarifications K9. Thanks providing the background links. Rezvilutamide is most comparable to Darolutamide. Hoping they will be approved in China and becomes available inexpensively via black market shipping by crafty entrepreneurs.. probably not!. Would still opt for Abi or darolutamide to add to ADT when my BAT finally fails.
And what makes you think BAT is going to fail? Postivity all the way down is the way to go. Rediger's book is proving to provide the sort of medical matrix that Wilber's did for my spiritual/philosphical world. Highly recommended reading and very timely for Moi.
Octber in AZ should be a great time! See you there. Paz - K9
Not thinking that BAT will fail, just considering how I may modify if need be and develop further options. PC is a highly adaptive beast and relentlessly explores options to adapt and surmount any therapy is thrown at it continuously without killing it. So I relentlessly explore and actually enjoy the learning that accrues. The collateral beauty of surviving and thriving.
I got a 5 Day Prolon FMD box and started it today. I'm skeptical that it is actually any better than a self designed fasting regimen. But thought I would give it a test as an experiment. So far I am not impressed except as to their marketing and packaging.
Day one (adding up the components) includes 1,050 Cal. 66 grams fats (600 Cal); 100 grams Carbs of which 28 grams are fiber (360 Cal carbs); 25 grams protein (125 Cal). Also some herb tea bags, 400mg of Algal oil DHA Omega 3. and multivitamin/mineral supplement. Seems like more of a low protein 1000 Cal diet than a fast. I don't see how this can trigger the same low-nutrient pathways as a modified water fast.
I haven't researched Longo's FMD in any depth but given the breakdown of what is supplied it would be interesting Paul to compare, at least in theory, if it's any better/different than Michael Mosely's The Fast 800 or the Optfast/Optislim shakes. Expect the difference might be in what is actually supplied. The Mosely program you have to organise the food yourself though and isn't exclusively plant based....but it can be. Don't think many would think of either of the Opt's as fasting though. I'll be interested to read your follow up.
Well, the latest research seems to indicate the the benefits of intermittent fasting and time-restricted eating comes mostly/all from their caloric restriction vs the fasting periods. It seem to me that the best dietary goals are to eat calorie-dense foods and get fiber intake well above recommended daily minimums of 25 - 28 grams for women and 31 - 34 grams for men. Hitting those targets will assure more whole plant foods (non-processed & more fiber) and less animal products (calorie dense but ~ZERO fiber) regardless of dietary preference.
The fiber is what the microbiome needs, so for most people that should be priority #1. Fiber comes almost totally from plant foods, so getting fiber to recommended levels is a guarantee that you will be eating mostly plants. And remember that when it comes to counting those dastardly carbs, fiber grams can/should be subtracted from total carbs in considering any dietary F/C/P targets.
BTW, I am on day 3 of my water only fast (just zero calorie liquids, actually - with some baking soda + ionic zinc/trace mineral infused water along with straight H2O, morning black coffee, and straight herbal/green tea.) This is my second 3+ day fast and as most "fasters" know, after about 48 hours, all hunger signals disappear and with no energy going to digestion, one feels pretty good. I'm going to hold out until dinnertime tomorrow and go for a full 4 days this time around.
That should give me a full 2 days of 100% ketosis and a good liver/kidney flush to boot.
That is good. I did subtract fiber from CHOs to calculate macros. Still more carbs than I am used to and would keep me out of ketosis entirely. So I'm not sold on Prolon. Agree that a water fast, or modifications with very low macronutrients is likely better. I do not see that they have proven FMDs to provide the same benefits. Just hoping to, and selling a bundle.
Don't understand your first sentence: "Well, the latest research seems to indicate the the benefits of intermittent fasting and time-restricted eating comes mostly/all from their caloric restriction vs the fasting periods."
If you mean the recently published trial of TRE vs unrestricted timing of equivalent total calorie diets and looking only at weight loss (showed no difference, "no benefit of TRE" - no surprise there). That completely overlooks the non weight-loss benefits of TRE / IMF via nutrient sensing pathways, epigenetic modifications and metabolic re-programming. Basically the entire basis for benefits that have been demonstrated in all species studied, and are being further explored, especially in the longevity and health protective spheres. To me that is a body of research that cannot be undone and discarded at this point. Only explored further.
In full agreement re: fasting for weight loss vs metabolic/cellular benefits. However, with the latest CDC numbers showing 40+% the US adult population as being obese and almost 3/4 overweight, much of the interest (and, therefore, research) is focused on the use of fasting routines for weight-loss.
With a BMI in the 21-22 range, like you, my reasons for fasting have little to do with loss of weight - and I will be eating to quickly regain any that I lose as a result of my current fast. As I have mentioned previously, Longo argues for his FMD based on the simple fact that most people will not maintain a more restrictive fasting routine. He claims there are numerous trials currently underway to test FMD routines for efficacy, so the proof may be forthcoming - to the extent that such trials of dietary interventions can provide proof.
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