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There are factors that resist enzalutamide effectiveness

Charles (Chuck) Maack

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Interesting information for those prescribed enzalutamide (Xtandi) as part of their androgen deprivation (ADT) regimen and appearing to show little effectiveness.


There are factors that resist enzalutamide effectiveness but with the addition of Metformin that resistance can be reversed and sensitivity of enzalutamide activity restored.




By using C4-2, CWR22Rv1 and LNCaP cell lines, as well as mice bearing CWR22Rv1 xenografts treated with either enzalutamide or metformin alone or in combination, we demonstrated that metformin is capable of reversing enzalutamide resistance and restores sensitivity of CWR22Rv1 xenografts to enzalutamide. We showed that metformin alleviated resistance to enzalutamide by inhibiting EMT. Furthermore, based on the effect of metformin on the activation of STAT3 and expression of TGF-beta 1, we propose that metformin exerts its effects by targeting the TGF-beta 1/STAT3 axis."

According to the news editors, the research concluded: "These findings suggest that combination of metformin with enzalutamide could be a more efficacious therapeutic strategy for the treatment of castration-resistant prostate cancer."


DISCLAIMER: Please recognize that I am not a Medical Doctor.  Rather, as a medical detective, I have been an avid student researching and studying prostate cancer as a survivor and continuing patient since 1992.  I have dedicated my retirement years to continued research and study in order to serve as an advocate for prostate cancer awareness, and, from an activist patient’s viewpoint, to voluntarily help patients, caregivers, and others interested develop an understanding of prostate cancer, its treatment options, and the treatment of the side effects that often accompany treatment.  There is absolutely no charge for my mentoring – I provide this free service as one who has been there and hoping to make your journey one with better understanding and knowledge than was available to me when I was diagnosed so many years ago.  IMPORTANTLY, readers of this paper must understand that the comments or recommendations I make are not intended to be the procedure to blindly follow; rather, they are to be reviewed as my opinion, then used for further personal research, study, and subsequent discussion with the medical professional/physician providing your prostate cancer care.




Charles (Chuck) Maack - Prostate Cancer Patient/Activist/Reduced Activity as Mentor (Because of age related health issues, had to limit what had been worldwide daily mentoring)

(A mentor should be someone who offers courtesy, professionalism, respect, wisdom, knowledge, and support to help you achieve your goals; would that I succeed)


Always as close as the other end of your computer to help address any prostate cancer concerns.


"What you leave behind is not what is engraved in stone monuments, but what is woven into the lives of others."


“A good character is the best tombstone. Those who loved you will remember. Carve your name on hearts, not on marble.”


   “Sepius Exertus, Semper Paratus, Semper Fortis, Semper Fidelis, Fraters Infinitas”

“Often tested, Always Prepared, Always Courageous, Always Faithful, Brothers Forever"


Recipient 2008 Us TOO Intl., Inc., Prostate Education & Support Network 1st “Edward C. Kaps Hope Award”

Recipient 2012 Prostate Cancer Research Institute (PCRI) “Harry Pinchot Award”

Recipient 2016 Us TOO Intl., Inc. Certificate for 20 Years Dedication/Inspiration


Email: maack1@cox.net

My website http://www.theprostateadvocate.com

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1 hour ago, Charles (Chuck) Maack said:

Interesting information for those prescribed enzalutamide (Xtandi) as part of their androgen deprivation (ADT) regimen and appearing to show little effectiveness.

A very good post Chuck, many thanks. I'm on Zytiga and don't know how long for, and maybe might have Xtandi later, but someone said Xtandi was like Cosudex, bicalutamide, but stronger. In early 2016, after 6 years on normal ADT with Lucrin injects, it began to fail.

By July I had additional IMRT to PG and started Cosudex, but that only worked for 6 months. I may never have Cosudex again but I wonder if metformin or anything else would improve blocking action of Cosudex. I have next Psa next Monday, and apparently cannot see my onco doc because he's ill, and have to talk to intern in about 10 days, and most are just not on the ball.

Your post says you have been fighting Pca since 1992 ! Wow, that's 25 years. Amazing.

All the best,

Patrick Turner.  

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While on Zytiga/abiraterone acetate I continued Lupron/leuprolide and Avodart/dutasteride.  With Zytiga/abiraterone acetate developed to block testosterone production from the three sources (testicular, adrenal glands, and that androgen/testosterone that cancer cells can produce themselves) - wherein LHRH agonists or antagonists only block testicular production - I was able to manage control my very slow PSA rise for several years all below 1.0ng/ml.  Having also read that Metformin can have a synergetic effect on Zytiga to enhance its effectiveness, I gave that a try that worked for awhile, but eventually my PSA elevated to where I discontinued the Metformin since that synergetic effect obviously was no longer effective.  By the time my PSA that had been below 1.0ng/ml for several years with a good drop but then eventual very slow rise up to the 0.9ng/ml range my MedOnc and I decided to stop just the Zytiga and turn to a try with Xtandi/enzalutamide that served a different purpose of, as you note, a supposed super anti-androgen much more powerful than Casodex/bicalutamide to block the multitude of androgen receptors on cancer cells from androgen/testosterone access.  With continuing the Lupron/leuprolide and Avodart/dutasteride and now changing to Xtandi/enzalutamide, there was only very brief effect of lowering my PSA slightly before the PSA again began to rise.  That is when my research found the paper I provided in my earlier post that Xtandi/enzalutamide may be more effective with the effect Metformin may have on issues causing blocking of the Xtandi effect.  Thus, by again giving Metformin a try, but this time with Xtandi, I should know more next week with a PSA test scheduled to see if such an improving effect has occurred.  Monitoring various Prostate Cancer research sites and reading, reading, reading can sometimes find solutions otherwise not brought to our attention.  So we do so, pray, and continue researching.  What I learn that makes sense, I pass on to as many other prostate cancer patients/caregivers for which I have email addresses for their further research and discussion with their treating physician.  Wishing you well, Paul!  

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Oops.....I meant "PATRICK" for my reply!  I am working with so many patients that I occasionally (thankfully) make such slip-ups in names.  Sorry, Patrick!

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2 hours ago, Charles (Chuck) Maack said:

I was able to manage control my very slow PSA rise for several years all below 1.0ng/ml.

Hi Chuck, 

I had to read that twice because you say Psa later rose again to 0.9, after being below 1.0, so I guess it was considerably below 1.0.

I get next Psa result next week, and will see radiation doc on 16th, and onco doc on 21st, and present the request for 5A4 Avodart dutasteride. My GP knew about this stuff, and said it may be good idea, so, we'll see.

But tomorrow, I am cycling 45km from here to a winery with a restaurant with maybe 20 others, having morning coffee and maybe a muffin, then returning 45km same way. Probably take me nearly 4 hours, but I see no reason to quit the cycling until cancer or treatment side effects push me off the bike. I never pray on a Sunday, but celebrate Nature by just being within its Wonderment with little need for words. But this arvo, Saturday, there's a concert by 30 musicians playing classical music ( violins and cellos, flutes ) at a local Anglican Church with beautiful acoustics and it is there I witness the magnificence of humble achievements of others. It is a highly contemplative time that brings peace of mind away from the distracting violent and silly world that is over-reported to us daily. 

I went to their June concert which featured Baroque period music, I was recovering from double TKR, and somehow the moving experience reset my mind. I missed the August concert, but I need to re-set again. Its not the words that count, its the music, and just being with quiet gathered group........   


I think you are right to keep researching yourself, difficult today, in a world which mostly refuses to focus for longer than a Tweet, and which is obsessed with emotions and avoids nitty-gritty details.

To all, I say keep as well as you might, and I know it is difficult,

Patrick Turner. 


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