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Adaptive Therapy as it applies to the treatment of cancer: Part One - A Personal Perspective

cujoe profile image
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This is a multipart post. The part herein is a general introduction to the concept of Adaptive Therapy as it applies to the treatment of cancer. The subsequent post(s) is(are) about recent research efforts that model the theory and provide clinical evidence of it's efficacy for PCa.

Linked below is a Jan 2020 article in the WSJ that gives a good non-technical overview of Adaptive Theory (AT) that was developed by Dr. Robert Gatenby. Also linked is an earlier 2019 article in Wired that profiles the work of Dr. Gatenby in greater deatil, first at Fox Chase in Philadelphia, Arizonia University, and since 2007 at the H. Lee Moffitt Cancer Center in Tampa, Florida. Dr Gatenby is the major trail-blazing pioneer in the development of AT and is using it to treat appropraite patients at Moffitt.

I think some form of AT is being done by a lot of cancer patients without them even realizing it. In fact, up until I first found out about adaptive therapy several years back, I was inadvertently doing a form of it with my ever-changing supplement regime. That was partly due to the availability of better research on supplements and the advent of my second cancer, creating a need to expand my self-directed complementary interventions to affect them both.

Those reasons have caused me to frequently change combinations and dosages of supplements year in and out. Since I got my first cancer diagnosis (CLL) back in 2006, I have been at this for 15 years now, so the range of modifications to my diet, lifestyle, and supplement regimes has been quite wide over that period of time. There is no way of knowing if any of this has had any significant influence on my inexplicably better than expected outcomes for both cancers. But AT could easily be at work at some level.

Circumstantially, I also am doing a n=1 trial on PCa SOC, as I have done a single ADT treatment and been off treatment and < 0.1 undetectable (0.02 new nadir last year) for over 3 1/2 years. So, even with SOC, I am practicing a form of Adaptive Therapy; i.e., with no "induction period", my early ADT vacation is definitely not SOC - even for IADT). Time will tell whether my extended vacation is durable or fleeting, but at 73 years old, I am comfortable with my decision to put QOL above the "promise" of better long-term outcomes with SOC continuous treatment. (with the many debilitating side effects that go with it.)

Those of us who have had cancer for many years and seen its effect up-close in family and friends know that each of us walks our own individual road when it comes to how and when to treat it. Most cancer centers follow the same or similar rulebook. My departure from the SOC rulebook was due to a inadvertent lapse at my treatment center.

That lapse opened up the opportunity for me to explore a path that now seems a logical possible option for ADT "good responders". In my case the ADT was the bicaludamide 4-week "flash-bridge" to a 3 mo Lupron depot. With an excellent response at the end of 3 months, I made the decision to see see what T and PSA looked like after 3 mos off ADT. At the end of the single 3-mo treatment period, my T was 9 and PSA was <0.1 undetectable, down from 25.5 just prior to starting ADT. Following my 3-mo treatment vacation, PSA remained <0.1 undetectable and T had risen to a post-diagnostic high of 586! (Note: If my PSA HAD risen above my treatment center's <0.1 "undetectable" level, I would still have had the option of repeating the cycle again or doing a full induction cycle. Either way, it is unlikely that in that amount of time the cancer would be out of control - vs the possibility of the 3 1/2 + year extended vacation I have had.)

In summary, my experience would seem to provide n=1 evidence that "good responders" are risking driving their cancer to CR with continuous ADT (and often being miserable in the process), when in fact they could get by with lengthy (in my case, multi-year) vacations while maintaining normal T levels and excellent QOL. Embracing AT as an approach to cancer treatment, would offer some subset of PCa patients the options of challenging their cancer without pushing it to early CR status. Readers here should note that I am NOT suggesting this is a sound strategy for patients with metastatic disease or aggressive pathology (altho' my profile is pretty aggressive), but rather that it is a strategy that seems to embrace the concept of AT from the start of treatment and offers an option for some percentage of patients to retain a QOL that is closer to that of an untreated man for indefinite periods of time.

Here is a link to the WSJ article (The quote below from the article, which refers to the use of AT in pest management, may unfortunately summarize where we are in our approach to cancer management today):

* * *

“I think pest managers are about 30 years ahead of the oncologists,” said Carlo Maley, an evolutionary cancer biologist at Arizona State University and director of the new Arizona Cancer Evolution Center."

* * *

A New Approach to Cancer Treatment Draws Lessons From Darwin ‘Adaptive therapy’ uses principles of evolution to try to manage cancer as a chronic condition - By Brainna Abbott - Jan. 7, 2020 **

wsj.com/articles/a-new-appr...

** If the WSJ link blocks access to full article, try this alternative link

pressreleasepoint.com/new-a...

And here is the must-read lengthier Wired article about Dr. Gatenby's work:

A Clever New Strategy for Treating Cancer, Thanks to Darwin - by Roxanne Khamsi - 03.25.2019

wired.com/story/cancer-trea...

Stay Safe & Well - and Be Darwinesque Adaptive in your life and the way you think about your cancer.

Ciao - Capt'n K9

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cujoe
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cujoe profile image
cujoe

Yes, I even referred back to that post for this one. As you should know by now, you and your sidekick are always ahead of the pack when it comes to creative alternatives to SOC. Adaptive Therapy first caught my attention in a post by Kuanyin at APC about three years back. My reason for this post was to educate newcomers and skeptics of the possible advantages of thinking outside of the SOC box.

That Dr. Gatenby is using AT at Moffitt is a real promising departure from that semi-rigid SOC rulebook we all have to deal with at most treatment centers. (The exception being when we volunteer to be their human mice for a clinical trial.). Much like Dr. Abraham Morgentaler and his clinical explorations into the role of T in PCa (and, importantly, patient QOL), Gatenby is also challenging the status quo. AT seems to me an obvious strategy to consider, as I have watched family members run the gamut of cancer drugs that one-by-one lose out to resistant cells over time. The terminal state is when the drug list is exhausted and the patient a shell of his/her former self. AT offers the possibility of extending the effectiveness of cancer treatments and maybe letting us kick the bucket from a less physically and emotionally degrading cause.

Just my individual point of view. Deciding to depart from SOC is a difficult decision - and not one to be taken lightly. We are indoctrinated to think that "experts" always know better than non-experts when it comes to complex issues. In medicine, the non-expert would be us? (You have to decide yourself, if that is true for you.)

Stay Safe & Well - Captain K9

PS - As much as I would like to bread bread with the two local PCa sages who live in my personal hero writer Thomas Wolfe's hometown, I might not be able to swing a lunch/dinner date on short notice. That said, I do have a couple of appointments in the Triangle within that time frame. However, it's still a pretty long haul from there to Mr. Biltmore's table, but . . . hey, it could happen.

BTW, I trust the move-in went well and you & Ms. Mary are at least starting to put your summer home back in order.

6357axbz profile image
6357axbz

Are you able to reduce your message to a readily understandable summary that can potentially benefit the majority of us incurable cancer patients?

cujoe profile image
cujoe in reply to6357axbz

Sorry, but no. I take my cancer(s) seriously and have invested a fair amount of time putting the post together. If the topic seems relevant to the reader, I expect them to have a similar level of interest and be willing to invest a lesser amount of time looking into information provided.

For anyone unwilling to read such a short post and two relatively short and relevant linked non-technical articles, either one of which might help them make better choices about treatments for their disease, I can only assume the topic is not really of interest to them.

BS/SW - K9

addicted2cycling profile image
addicted2cycling in reply tocujoe

cujoe AND Nalakrats 👍👍 for your posts

1st a >>> GOOD LUCK TO ALL!!!!

here's what I guess would be my "ADDAPTIVE THERAPY" for GL10 as I was approaching my 65th birthday>>>

diagnosed 6 years and 2 months ago

CASTRATION 6 years and 1 month ago

first CRYOABLATION 6 years ago

second cryo PLUS experimental immuno injection 6 years ago come December

BEGAN Testosterone injections 6 years ago come January

HAD another Testosterone injection 2 days ago AND BICYCLED 50.05 MILES hours later

might be hastening my death but am GOING OUT LIVING AS HIGH A LIFE AS I CAN

btw --- I am "IN AWE" of y'all out there and do not want my post to be taken in any other way but MY explaining a radically different AND LIKELY STUPID PATH TAKEN BUT ULTIMATELY expressing my feelings towards this PCa as being >>>

"to hell with it --

-- I WILL LIVE MY LIFE MY WAY --

-- since I am gonna die anyway"

cujoe profile image
cujoe in reply toaddicted2cycling

Addicted2cycling,

I no longer post at APC, so your reply gives me the opportunity to tell you what I have been unable to do for some time . . .

"No one gets out of here alive" - and following your history via your many heartfelt posts, I think it is safe to say that few here know that better than you do.

Your positive attitude and physically persistent challenge to a state that would cause most to throw in the towel and give up, provides true inspiration to all who read at these forums. You willingness to share the details of your journey is a tribute to your unfailing spirit and determination to maintain your humanity through the darkest of times. We learn much from each other and our sharing makes us better people and a stronger community.

As for your path, like for most of us, it was done day-by-day, making the best decisions possible with the information available at the time. Living in the ever present "now", we do better when we look not back to the past or try to fathom an unknown and unknowable future. I have been bedside for the last breath of both of my parents and two of my siblings, all from some form of cancer. So when my time comes around, I will be loaded with T and riding right there along side you, Brother - "GOING OUT LIVING AS HIGH A LIFE AS I CAN".

Keep your spirit high as you ride when you can. Day at a time, no more , no less. Keep it safe and mind the speed bumps. Best regards - Captain cujoe

Cicero2K profile image
Cicero2K in reply tocujoe

Dr. Gatenby interview by Dr. Peter Attia recently here: quite an education. I start ADT/Xtandi soon. podcasts.apple.com/us/podca...

cujoe profile image
cujoe

We all had a difficult 2020, but yours was a humdinger. Recognizing the misfortunes and hardships of our fellow men (and women), is what makes us human.

NEVER LET A TREATMENT FAIL! I Love it! Words to repeat every day. I did take one year of engineering math & physics at our in-common NCSU, but when I switched out of Product Design, I only needed cookbook math/chemistry/physics. A very happy day for Moi. Calculus, differential equations, statistics, probability . . . I fully appreciate their value, but entrust people like you to do the heavy mental lifting needed to use them. I'm basically a "pattern guy"; always looking for Bateson's Pattern That Connects combined with a measure of Wolfe's "a stone, a leaf, an unfound door . . ."

Now that you are settled enough to socialize with the riff-raff from down east, I'll see what I can do to make a lunch date in your neighborhood. I'll keep you posted from my end. K9

Cooolone profile image
Cooolone

Compelling and certainly thought provocative for all of us that fall within that "kill it all" mentality, myself included! I have come across a few references in my readings over the last few years and mainly BAT as a form of this ideology in regard to keeping the cancer cells off center and susceptible to therapy whereas otherwise failing.

Thank you for posting!

*As an aside, the WSJ article is by subscription only, unfortunately unable to read it :(

marnieg46 profile image
marnieg46 in reply toCooolone

I was able to open and read it so maybe have another try as it was very interesting.

cujoe profile image
cujoe in reply toCooolone

Thanks for catching this problem. WSJ is sometimes accessible for free and sometimes not? I just tried the link and was also blocked from the full piece this time. I am often able to find articles such as this one reproduced elsewhere by doing a search of the article title. In this case I got it, minus the photos, here:

pressreleasepoint.com/new-a...

I will add the link to the post as a second option. BS/SW - K9

Cooolone profile image
Cooolone in reply tocujoe

Yes, I'm search ng "Adaptive Therapy" and have come across a lot of information, no worries! Lots to read about... Again, very interesting ;)

cujoe profile image
cujoe in reply toCooolone

Just watch out for that rabbit hole just ahead.

NPfisherman profile image
NPfisherman

K9,

Great article.... here is an article on game theory and cancer treatment--avoid resistance by treating for a while and then stop... allow non-resistant cells to regrow....rinse and repeat...

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

The idea that one poster gives out from a Maha Hussain study in 2015 that continuous treatment is better does not account for the evolution of treatment... Looking at the ORIOLE trial results, the individuals with no mutations had 2 years of no treatment post SBRT without a recurrence, and that bodes positively in slowing down castrate resistance... no treatment, no resistance...

Have a great day....

Fish

cujoe profile image
cujoe in reply toNPfisherman

NPfishless,

I'm pretty sure that paper is the one in the post by Kuanyin at APC that first got me interested in AT. It seem clear now that Dr. Gatenby has taken the AT ball and is running full-speed with it at Moffitt. Part Two of the post reports on his work to develop models that can be used to customize treatment protocols for individual patients. (That may be what Nal's referring to in his earlier reply above.) Softer science with hard math underpinnings - but it is still coming.

Good to have you back, Amigo - k9

cujoe profile image
cujoe

Congrats on the good labs and the return to your home, sweet home. That's more than enough to justify a bit of playfulness. You'll maybe see why i took the differential equation bait when Part Two gets posted. You may find you are not so far off with your playful modeling.

BTW, I'll be hoping for the same 2x confirmations (undetectable PSA and unfailing vacation) on 10 June.

Now, go get all those picture rehung and the boxes out to the dumpster.

K9

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