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Enzalutamide synergized by Metformin

Charles (Chuck) Maack

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Have you recently been prescribed enzalutamide/Xtandi and your PSA continues elevation? You may want to consider asking your treating physician to prescribe Metformin to synergize the effect of enzalutamide as concluded in the following paper. I am currently giving this a try with Metformin ER (extended release) 500mg one tablet in the morning, one tablet at bedtime in combination with enzalutamide/XTANDI since initially it appeared enzalutamide without Metformin was effective with a slight drop in PSA level, but then a slow rise.


Metformin reverses prostate cancer resistance to enzalutamide by targeting TGF-β1/STAT3 axis-regulated EMT.




Metformin reverses prostate cancer resistance to enzalutamide by targeting TGF-β1/STAT3 axis-regulated EMT. - PubMed - NCBI


Cell Death Dis. 2017 Aug 24;8(8):e3007. doi: 10.1038/cddis.2017.417.



It should be noted that Metformin can affect the absorption of Vitamin B12 in the system, an important Vitamin as explained in the following paper (and there are many other papers reporting the same), thus one’s Vitamin B12 level should periodically be determined and prescribing of Vitamin B12 considered if the appropriate level is below normal: http://www.pcosnutrition.com/vitaminb12/

PCOS Nutrition Center Articles/Blog


Strong evidence is showing metformin depletes levels of vitamin B12. Here's what to do.



Having been on various androgen deprivation medications and associated therapies relatively successfully over the past 21 plus years, my current prostate cancer therapy, having had a great response with Zytiga/abiraterone acetate that eventually failed after 5 years 8 months, is Xtandi/enzalutamide 4/40mg capsules (160mg) once daily, Metformin ER one 500mg tablet twice daily, continuing Lupron/leuprolide acetate 45mg injection every 6 months, continuing Avodart/dutasteride one 0.5mg capsule daily, continuing Cabergoline/Dostinex 0.25mg one tablet Monday, Wednesday, and Friday, and denosumab as Prolia 60mg subcutaneous injection every 6 months.


An added consideration for those prescribed Avodart/dutasteride and have been taking this medication for 4 to 6 months is recognizing it will have established itself in your system.  In so doing, you can then change to taking the 0.5mg capsule every other, or even every third day and it will remain just as effective as daily because of its long half-life.  This can be a consideration in cost saving if you don’t have health insurance coverage for oral medications. The half-life of Avodart is 5 weeks, and it can take 4 to 6 months for the medication to be totally eliminated from the system once it is stopped.


See: http://www.drugs.com/pro/avodart.html and scroll down to “Pharmacokinetics”

Avodart - FDA prescribing information, side effects and uses


Avodart official prescribing information for healthcare professionals. Includes: indications, dosage, adverse reactions, pharmacology and more.



DISCLAIMER: Please recognize that I am not a Medical Doctor.  Rather, I do consider myself 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 deep research and study in order to serve as an advocate for prostate cancer awareness, and, from an activist patient’s viewpoint, as a mentor to voluntarily help patients, caregivers, and others interested develop an understanding of this insidious men’s disease, 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 their journey one with better understanding and knowledge than was available to me when I was diagnosed so many years ago.  IMPORTANTLY, readers of medical information I may provide are provided this “disclaimer” to make certain they 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 their prostate cancer care.

Charles (Chuck) Maack - Prostate Cancer Patient/Activist/Mentor

(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


 Published papers:

“A Wake Up Call To Men & The Women Who Care For Them” JCPCR-06-00189 Volume 6 issue 1 - 2016: http://tinyurl.com/3djfgve

“A Prostate Cancer Patient’s 24-Year (1992-2016) Continuing Journey from Diagnosis to Treatment to Recurrence to Mentoring” JCPCR-04—201604 Volume 4 issue 4 – 2016:  http://tinyurl.com/hcxuxv9

“Newly Diagnosed with Prostate Cancer? - A Mentor/Patient Discussion” May 23, 2017 Biomedical Journal of Scientific & Technical Research (BJSTR) http://biomedres.us/pdfs/BJSTR.MS.ID.000110.pdf

“Prostate Cancer Advocacy and Mentoring Support” – published November 22, 2017 in the journalHolistic Approaches in Oncotherapy” HAOT-17-OPN-0004 1.1 (2017): 14-15;  https://scientiaricerca.com/srhaot/pdf/SRHAOT-01-00003.pdf


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