This trial appears to support the use of Metformin and Statin for men with MCRPC.
Effects of Metformin and Statins on M... - Advanced Prostate...
Effects of Metformin and Statins on MCRPC
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EdBar
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"Within the limitations of post-hoc sub-analyses..."
That is exactly the problem with all non-randomized retrospective studies - SELECTION BIAS.
It’s another point of view, keep an open mind.
Ed
Points of view don't matter to science. That study doesn't measure up, but STAMPEDE will.
• in reply toTall_Allen
Nice trial. stampedetrial.org/
What I think EdBar meant was that different people have different goals.
If your goal is the quantity of life and you will take whatever pain, etc, is needed to get more quantity you have a certain view of therapies. If your goal involves your personal quality metrics as well as some quantity, you'll have a different take. And of course, there are some guys who don't want to sacrifice anything and are willing to die rather than give up what they define as quality (I've talked to a couple of guys who were going to abandon all SOC therapies and start doing whatever they wanted to do). All of these viewpoints are valid IMO. I'm somewhere in the middle. I would like to live for 12 more years and set a good example for my son while I'm here.
EdBar• in reply to
And the fact that Metformin is a cheap (practically free) drug that’s been around forever, was recommended by a PCa specialist and has little or no side effects. Why anyone would have such a problem with it baffles me. My variety of PCa is the aggressive, life threatening form so if there’s a chance that an innocuous drug may help extend my life I’m gonna take it. Someone who doesn’t have a life threatening form of PCa probably wouldn’t understand that.
Ed
Good point Ed. With little downside why not. My first MO at MD Anderson suggested it to me.
• in reply toEdBar
I'm waffling on it simply because it has some gastro sides. My current MO discusses the potential mTOR and other avenues in which it might be helpful. My Mayo urologist begged me never to take it. He was one of the guys who told me that high dose estrogen wouldn't reduce my T to castrate levels - he pleaded and almost convinced me. Almost... High School biology still rules! So I plan to talk to my MO again and get a more definitive answer about my specific situation. I'll let you know what she says.
As you said, we have life-threatening cancer and it is an entirely different ballgame. If we want to live with our definition of QoL we can't afford to wait for proof of efficacy or lack thereof for every single drug and therapy. Sometimes we need to take our punches based on limited and sometimes very speculative information.
Seasid• in reply to
How much metformin are you taking per day? My only problem with taking metformin is that I don't know how much vitamin B supplements should I take with metformin? I believe we shouldn't supplement too much of vitamin B 12 if we have a PC.
• in reply toSeasid
I usually take zero. Sometimes 1000 and sometimes 1500. I'm going to try to get a little more definitive answer from my MO.
High doses of B-12 or folate might not be good. I'm mostly vegan but my B-12 is pretty good. I supplement with 100% RDA of methylcobalamin every other day. I get that and methyl folate in a low-dose multivitamin that I take. smile.amazon.com/gp/product...
I’m taking 1000mg twice a day, per Snuffy Myers, been taking it for about 8 years now. Just a word of caution on B12 supplements, my PCa specialist, Dr. Sartor, advised against it, saying “prostate cancer loves it “.
• in reply toEdBar
As Mio says, look into care oncology. Science-based - but perhaps not the level of SOC evidence required by some. But if you are under the threat of a mortality-ending disease, you don't always have the luxury of being as choosy.
I used Care oncology for a few months and then dropped them. They made a good suggestion that I follow today. Other than that it is statins and metformin.
I found that the initial consult was very valuable but they charge high fees for the drugs and the follow-ups were useless for me.
• in reply toEdBar
Thanks EdBar. I think the same. PCa is going to love getting it. But we do need it to live so I want to stay in the low-normal range. Methylated B-12 should be safer than cycanocobalamin.
You need to test your vitamin B 12 levels, otherwise your red blood count could be effected:What are the dangers of taking metformin?
Commonly reported side effects of metformin include: lactic acidosis, diarrhea, nausea, nausea and vomiting, vomiting, and flatulence. Other side effects include: asthenia, and decreased vitamin b12 serum concentrate. See below for a comprehensive list of adverse effects.17 Dec 2021
drugs.com › sfx › metf...
Metformin Side Effects: Common, Severe, Long Term - Drugs.com
I’m gonna just take the advice that Dr. Sartor gave me, I don’t think there are any doctors out there who are more knowledgeable when it comes to PCa. I was just sharing a comment he made the choice you make is up to you.BTW I haven’t experienced any of those side effects even at 2000mg a day.
Ed
• in reply toSeasid
Your right, stay light on B. Metformin 500 mg morning with food and after two weeks every evening with dinner. I researched day and night for the proper supplements as well. I hardly slept, both my daughter and I compared studies notes. His quality of life is good. He feels no pain and has Mets to his bones and some other places. If this is right for you, look into Care Oncology.
• in reply toEdBar
For sure, Ed
• in reply to
Yes RSHI.. So true. Jim is on Metformin. His docs don’t know, it’s better that way! Why have a million Allen’s beating you down. Jim is different now, he’s stronger and is able to work outside on his feet all day long. He is back to doing light bench press. Metformin is cheap, been around for a long time.
London441• in reply to
You make a good point as far as it goes. Endless debate on the efficacy of metformin, statins etc on PCA won’t be easily resolved for some time if ever. I’m less interested in that.
What does interest me is this notion of decisions driven by quality vs quantity of life. To me this is truly shape shifting territory, because a man can say ‘well I’ll do this but not that’ or ‘longevity means more, it means less, just care about QOL and on and on-only to find that the ethic in question often does an about-face when the s**t hits the fan, so to speak.
Tough talk about putting QOL first can easily disappear when the going gets as tough as the talk. By the same token, one’s penchant for longevity at all costs often doesn’t look so appealing when QOL becomes minimal or worse.
Not a pleasant subject perhaps, but IMHO one we should consider carefully.
• in reply toLondon441
I talked about the QoL vs. Quantity thing in a post a while back. I don't view my thoughts as tough. I have said that being a tough person would involve being able to gut out ADT or whatever you need to so that you can be there for your family.
And I also admitted that when the s..t hits the fan, I might throw in the towel and do whatever I can to eke out some more lifeless life. However, there is a chance that I won't. I know of some guys who decided to just do what they want - knowing full well that they are doomed to die earlier. One of these guys had fairly advanced cancer.
I know that my personal choices are swayed by my spiritual beliefs and my kids. I have a 9 year old and need 12 more years to get him through school and I want to set an example for him. He jumped on an exercycle when he was 6 months old and started pedaling away! He flexes his muscles constantly and talks about getting ripped. He has a big heart and lets younger kids beat him when they compete in Jiu-Jitsu because he doesn't want them to feel bad.
London441• in reply to
My comments weren’t directed at you sir. I like your commitment, your conviction. Many fall short in the attempt, that’s all I’m saying. Carpe Diem!
• in reply toLondon441
Thanks for letting me know. I wasn't offended though. It's something that I have thought about. Easy to talk the talk. Can we walk the walk? And do we even want to walk that walk? For the time being, I am perhaps a little too comfortable at times choosing fitness and activity over PCa therapies. I try very hard to blend them and I try to improve them while at the same time making them easier for me to do. So far, so good. But since I don't have RCTs to tell me what might happen, I'm always on edge.
What exactly is stampede studying TA? Metformin versus a placebo? Statins vs a placebo ? Both vs a placebo? All of the above? Any timeline to some results ?
Schwah
Metformin+SOC vs placebo+SOC
• in reply toSchwah
stampedetrial.org/ The website includes its goals and data reviews.
They have an RSS feed so I get updates.
Most studies do not take the power of synergy into account. Even diet is based on the synergy of various nutrients and foods to maintain health and prevent disease.
Scurvy and goiter are just two examples of diseases brought about by insufficient diets, diets that lacked the nutrients to support each other for health.
Currumpaw
Snuffy would always talk about using a multidimensional approach to PCa, shutting down various pathways. Metformin is one tool in that approach.
Ed
My onco is the head of the genitourinary department at the hospital. He has decades of experience with thousands of patients. He has been overseeing my health for years. A couple years ago he told me, when I asked about dropping some of the things I do and take, he advised me not to change anything. He did not expect me to go this far without some type of farther treatment. I am stable. I will take that without complaint. In my meds and supps there is Metformin 2X and Atorvastatin 1X with the nightly Metformin. Synergy. Those who discount or deny the power of synergy may be too subjective and rigid in their beliefs of practices or in others, who promote whatever, to be objective.
I will continue to listen to the doc that gets the results of my lab tests --which are sometimes quite comprehensive and who has made graphs showing my history with this disease. Decades of experience? The head of the genitourinary department at the hospital--a teaching hospital for Brown University, (I have met a few young uros or uros in the making as they sat in on my appointments). He has cared for thousands of patients and been instrumental in the education of young uros and oncos. He has been involved in conducting guv acronym agency funded studies himself. I also have a conventional/alternative doc who has done quite a bit for me. He may be the reason why what I do has given me stability. As my onco said--"Don't change anything".
Over the years the "one trick pony" studies, which I once found impressive, I now look at very carefully. Cemeteries have many bodies which were treated with the very best SOC, alternative and questionable treatments and practices.
Currumpaw
• in reply toCurrumpaw
I don't know if metformin does anything on its own unless you have blood glucose issues. I think you need to combine it with a statin. And perhaps rapamycin or another mTOR inhibitor. Possibly even fasting would help too.
There are some RCTs with combinations. Overall they tell me that synergy is very real. Take two things that do nothing on their own, combine them and sometimes we get good results.
Currumpaw• in reply to
There are studies on Metformin about it's ability to be a youth type of drug. Telomeres! Would this be another reason to not take Metformin? Wouldn't want to stick around after the 401k is gone right? LOL!
Metformin: A Potential Candidate for Targeting Aging …
ncbi.nlm.nih.gov/pmc/articl...
Currumpaw
• in reply toCurrumpaw
Poor wife needs to keep working 
Currumpaw• in reply to
I like the way you think. A friend has a younger, attractive wife who is a QA specialist. He is an engineer. He blurted out one day that in addition to the fact that he loved her, he was depending on her to support him as she is a good 10 years younger. He said it jokingly, but he was stating a fact! He had better keep her happy! A very nice couple.
The TAME Trial--Nice! Thanks. This benefit of Metformin has been studied for years.
Whey protein also strengthens telomeres. Creatine strengthens T cells. Go figure. Move over Schwarzenegger!
Currumpaw
• in reply toCurrumpaw
SARMs, whey, Cardarine, YK-11, Stenabolic, creatine. One of my friends asked me how I was getting so muscular. I replied, "get prostate cancer".
I retired 6 years ago. My wife is 17 years younger and makes more money than I ever made. I think she's crazy hot and when I met her I thought that there was no way a girl like that could go for me. Every day I wonder how I ever got so lucky. I went through a lot of romantic grief to get here. And I'm doing everything that I can to keep her happy. Really weird though - she feels the same way. She felt that way when I was a scarecrow on ADT. She felt that way when she met me. I'm very blessed to be with her.
Purple-Bike• in reply to
Might you have any RCT on hand with a combination including metformin for those with excellent lipids, low body fat, low fasting glucose?
I quit metformin based on evidence that that as a stand-alone it is of no help to pca when lipids etc are fine.
• in reply toPurple-Bike
Unfortunately I don't. I am in the same boat.
Points of view matter to science...that is basis of all new creativities and breakthru..Same in medicin....Like epigenetics, methylation..
not thru chamical drugs but thru nutrition therapy.....diet and exercise is my medicin besides chemical drugs
Lot to understand the mechanism of disease and paths of cure which do not kill the patient by second effects...
Point of view is the key and we have to change the medical thinking which cures the disease but does not remove the cause
I believe in Patient power where patient takes his QOL in his own hands and doctor is one actor in his journey of life ..
Knowledge is the key but it includes all aspects of human living....
Scientific thinking is creation of my own conditioned mind....it has limits and is subjectivly objective.
• in reply toKarmaji
Yes I can’t tell you how this thread of comments have made me feel. It’s called hope!! If Jim sat home every day, in pain it would be the end for him.
I think that there is biological plausibility and research that show that metformin and statins can help people who have poor blood sugar, high lipids, and extra body fat. If this is the case, then this might explain some of the trial/study results. Statins are likely more beneficial to more people than metformin. Their standard use is for lipid profile benefits and therefore cardiac risk reduction. Most of us could benefit from a statin. Whether it helps with PCa directly or simply reduces cardiac risk.
I don't know if that is the case with metformin. My MO thinks that there might be benefits to both. But she does not go so far as to prescribe either one. However, if one of her patients is using one or both she won't talk them out of it.
I use a statin (40 mg of lovastatin). I'm on the fence about metformin. I don't know if it would help me or hinder me (my lipid profile is good, low body fat [but increasing ever since I went off of ADT], fasting blood glucose is low [70-90], I exercise and am active).
GeorgeGlass• in reply to
What’s your fasting blood glucose when on adt? Mine is 96. Before adt it was in the 70s. My diet is much healthier and low in triglycerides fat sugar etc.
It runs around 75. Cholesterol is around 145 (I take a statin). LDL, triglycerides all low normal range.
Ed
• in reply toGeorgeGlass
Doesn't look like it changed a lot. I was on ADT from 4/2019-9/2019. I do ADT-like phases during BAT+. There are a couple of higher spikes in the chart. I don't know what they are from. I was on SPT from 9/2019-8/2021. At the end of the chart I was on ADT and I was also doing Keto.
The low spikes in the chart are from the Keto diet. I do that every once in a while (colonoscopies and fat loss experiments - dud there: just a temporary loss of water).
BG vs. time
After about two years on 1000mg/d of metformin and atorvastatin 40mg/day of (both commenced as part of the Care Oncology protocol), I had to drop the metformin because it was making me vomit every couple of days - there was no change in diet or anything else, I think my body just defies it didn’t like it any more.
I also had to drop the Mebendazole from the CO regime because I kept being admitted to Emergency with a very swollen tongue that was choking me - I’d become allergic to it after a couple of years.
I was happy to stop both drugs because they were making me quite sick - but they did cure me from reading papers about PCa impacts of metformin and mebendazole!
• in reply toBlackpatch
That sounds terrible, I’m sorry you had to go through that pain and also the disappointment.
In general retrospective analyses are use to create hypothesis and stimulate controlled trials. It has suggested that statin and metformin might help in prostate cancer. Now, someone needs to do the controlled study. As a physician and scientist I have learned to be very wary of of retrospective studies. Also this effect size seems pretty small.
I’m just sharing information, I have no agenda, I’m not a doctor. I had an excellent doctor (Myers) prescribe Metformin for me and so far everything he’s prescribed has been working for 8+ years. Another (Sartor) tells me to keep doing what I’m doing. SoI’ll just keep doing what I’m doing.
Ed
Yes, Thanks Ed!
I posted the piece a while ago but was glad to see it again, following the attack on Metformin.
I have used Metformin for many years - first at 1,000 mg, & then at 2,000 mg (when the Swiss study appeared.) Dr. Myers is as much of a purist as TA, although Myers was a real-life researcher who actually conducted studies. He had nothing but praise for the Swiss study & was finally on board & very vocal in his support of Metformin.
-Patrick
A problem with STAMPEDE is the dose:
"All patients should aim to receive the target dose of 850mg BD."
The Swiss study used 2,000 mg,
Some studies (good and bad).
1. Effects of metformin and statins on outcomes in men with castration-resistant metastatic prostate cancer: Secondary analysis of COU-AA-301 and COU-AA-302 - European Journal of Cancer
ejcancer.com/article/S0959-...
2. Ongoing trial: Home | STAMPEDE
3. Castration Compared to Castration Plus Metformin as First Line Treatment for Patients with Advanced Prostate Cancer
clinicaltrials.gov/ct2/show...
4. Current Status and Application of Metformin for Prostate Cancer: A Comprehensive Review - PMC
ncbi.nlm.nih.gov/pmc/articl...
5. The effect of metformin therapy on incidence and prognosis in prostate cancer: A systematic review and meta-analysis
nature.com/articles/s41598-...
6. Metformin and Cancer: Mounting Evidence Against an Association | Diabetes Care
care.diabetesjournals.org/c...
7. Randomized Phase II Trial of Exercise, Metformin, or Both on Metabolic Biomarkers in Colorectal and Breast Cancer Survivors | JNCI Cancer Spectrum | Oxford Academic
academic.oup.com/jncics/art...
8. Association between metformin use and risk of prostate cancer and its grade – PubMed
pubmed.ncbi.nlm.nih.gov/238...
9. The suggested chemopreventive association of metformin with prostate cancer in diabetic patients – PubMed
pubmed.ncbi.nlm.nih.gov/329...
10. Association between metformin medication, genetic variation and prostate cancer risk | Prostate Cancer and Prostatic Diseases
nature.com/articles/s41391-...
11. Metformin and Prostate Cancer: a New Role for an Old Drug – PubMed
pubmed.ncbi.nlm.nih.gov/284...
12. Metformin Inhibits Prostate Cancer Progression by Targeting Tumor-Associated Inflammatory Infiltration – PubMed
pubmed.ncbi.nlm.nih.gov/300...
13. Prostate Cancer News, Reviews & Views: Best Evidence So Far: Metformin Has No Benefit for Prostate Cancer
prostatecancer.news/2019/11...
14. Metformin + Prostate Cancer | Ask Dr. Myers
askdrmyers.wordpress.com/20...
15. Metformin in chemotherapy-naive castration-resistant prostate cancer: a multicenter phase 2 trial (SAKK 08/09) – PubMed
pubmed.ncbi.nlm.nih.gov/244...
16. Mechanistic Study of Inhibitory Effects of Metformin and Atorvastatin in Combination on Prostate Cancer Cells in Vitro and in Vivo – PubMed
pubmed.ncbi.nlm.nih.gov/287...
17. ESMO Virtual Congress 2020: Repurposing Metformin as Anticancer Drug: Preliminary Results of Randomized Controlled Trial in Advanced Prostate Cancer (MANSMED)
urotoday.com/conference-hig...
18. About STAMPEDE | STAMPEDE
stampedetrial.org/participa...
19. The journey of metformin from glycemic control to mTOR inhibition and the suppression of tumor growth
ncbi.nlm.nih.gov/pmc/articl...
20. Metformin and Prostate Cancer: Benefit for Development of Castration-resistant Disease and Prostate Cancer Mortality
ncbi.nlm.nih.gov/pmc/articl...
21. Exercise and Metformin in Colorectal and Breast Cancer Survivors - Study Results - ClinicalTrials.gov
clinicaltrials.gov/ct2/show...
22. Metformin Hydrochloride in Treating Patients with Prostate Cancer Undergoing Surgery - Study Results - ClinicalTrials.gov
clinicaltrials.gov/ct2/show...
23. Survivorship Promotion In Reducing IGF-1 Trial - Study Results - ClinicalTrials.gov
clinicaltrials.gov/ct2/show...
24. Castration Compared to Castration Plus Metformin as First Line Treatment for Patients With Advanced Prostate Cancer - Study Results - ClinicalTrials.gov
clinicaltrials.gov/ct2/show...
25. Metformin inhibits proinflammatory responses and nuclear factor-kappaB in human vascular wall cells – PubMed
pubmed.ncbi.nlm.nih.gov/163...
26. Metformin as a senostatic drug enhances the anticancer efficacy of CDK4/6 inhibitor in head and neck squamous cell carcinoma – PMC
If you buy into the theory behind the COC protocol, it seems that it is based upon a multiple point of attack theory. In theory each of the 4 meds work on different pathways of metabolism of the cancer cell. Its sort of like " whack a mole". To suppress only one pathway just pushes the cancer cell to mutate and move to another pathway to survive. So, it won't surprise me to see the Stampede results showing minimal effect. Just like its come to be known that the triple whammy of Lupron, Zytiga and Docetaxel are more effective than just a single drug approach, it stands to reason that just adding Metformin without the other 3 accompanying medications will result in sub par results.
Synergy isn't taken into account with these studies.
Having worked in pharmaceuticals for 14 years I do not believe that a drug as inexpensive as Metformin will get a fair shake when a study that finds the latest, greatest and very expensive is about as effective.
Currumpaw
Doesn't surprise me that there are multiple pathways other than the 3-4 that the COC meds address. The only published data from them actually shows improvement in glioblastoma patients, extending the survival rate almost 2 fold. The most prominent pathway it seems to miss is cell aptosis. I'm far from understanding the best practice guidelines of off label medication use. I would love to read your guidelines and recommendations. It appears that you have found some answers. I know you take a myriad of supplements outside of SOC. I have added some myself, but am still looking for answers. I am still doing SOC along with the COC protocol and hoping to continue to educate myself. Thanks for your feedback.
I've often considered and wondered about the glucose and lipid association with progression of PCa. Interesting as when I was originally diagnosed, both of those were out of whack! Treatment that followed only exacerbated the situation, going from being able to control through diet, to requiring drugs. This also occured with persistent PSA and eventual StageIV as the glucose and lipids got worse too. Even with diet ... So, I do currently take both Metformin and a Statin, along with Prescription Omega-3 (Vascepa)... Hahaha.
Anyways, the body is a funny thing, and my wondering was if and how all this cell signaling lent to the condition being created to help fuel the cancer (cancer controlling it), or was it present and created an environment for the cancer to progress.
The mind always wanders! And wonders!
Best Regards
Metformin and Statins and Porno Movies, three of my favorite subjects.......
Good Luck, Good Health and Good Humor.
j-o-h-n Saturday 05/28/2022 2:30 PM DST
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