Metformin: Preliminary Results of Tri... - Advanced Prostate...

Advanced Prostate Cancer

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Metformin: Preliminary Results of Trial in Advanced Prostate Cancer (MANSMED)

noahware
noahware

Not sure if this was posted here yet:

In a mini-oral presentation at this year’s European Society of Medical Oncology (ESMO) 2020 Virtual Annual Meeting, Dr. Reham Alghandour presented the results of the MANSMED prospective randomized controlled trial. This trial recruited men with high risk localized or metastatic hormone-sensitive prostate cancer. Patients were randomized in a 1:1 fashion to receive standard of care with combined androgen blockade using LHRH agonist and bicalutamide 50mg daily with or without metformin 850mg PO BID.

The primary study outcome was time to castrate-resistant prostate cancer and the secondary outcomes were overall survival and PSA response rate.

The authors recruited 124 of whom 62 were randomized to each of the intervention and control arms. Of a median follow-up of 18 months, 12 patients randomized to metformin died and 17 randomized to control disease.

In the assessment of the primary outcome, patients receiving metformin had a longer time to castration-resistant disease (median 29 months, 95% confidence interval 25 to 33) than those randomized to placebo (20 months, 95% confidence interval 16 to 24, p=0.01). This effect was most pronounced in men with high-risk localized disease and node-positive disease, marginal in those with low volume metastatic disease, and there was no benefit in those with high volume metastatic disease. There were no statistically significant differences in overall survival or PSA response rate.

urotoday.com/conference-hig...

29 Replies

I’m eating metformin to near toxic levels , 2000 mg daily, working with my A1C and getting a skin wound to heal. A1C down from 8.8 to 6.2 right now. It’s been making me pretty sick with unpredictable explosive diarrhea, maybe there is an up side to all this metformin sickness and torture. that’d be a good thing. My body hates this much metformin.

💪💪💪💪👍👍👍

George71
George71 in reply to Kaliber

3mg boron daily for faster wound healing

Kaliber
Kaliber in reply to George71

I stick with what my medical team wants me to do ... my bg is very unstable ( along with my bp and cardiac ) caused as side effects of adt. Had 3 surgeries on a skin cancer on my forehead and 3rd one ( big 5 inch wound ) wouldn’t heal fast enough , turned into giant angry red wound filled with black stringy stuff and stuff that looked like the yellow mold on cheese skin. Culture said it wasn’t bacterial. They cut the stitches and opened it to air and cleaned it out. Been dressing it with $10 apiece silver impregnated dressings. Been healing very slow. Team wanted me to lower bg . Been taking 500mg metformin for years no problem. They increased metformin to 2000mg daily and boosted it with daily glimepiride 5mg. I experienced near instant nausea , gas pains and unpredictable explosive diarrhea.... they kept me on it anyway saying I’d get used to it and symptoms would go away. That was two months ago and nothing changed so far. Been eating lots of Imodium and cleaning awful messes. The sick feeling being the worse part . It goes away if I back down to 1000mg a day but team says that’s too low. If this article is right , maybe there is an upside I didn’t anticipate... hope so. Thanks brother ...

💪💪💪✌️✌️

George71
George71 in reply to Kaliber

The trace mineral boron is a micronutrient with diverse and vitally important roles in metabolism that render it necessary for plant, animal, and human health, and as recent research suggests, possibly for the evolution of life on Earth. As the current article shows, boron has been proven to be an important trace mineral because it (1) is essential for the growth and maintenance of bone; (2) greatly improves wound healing; (3) beneficially impacts the body’s use of estrogen, testosterone, and vitamin D; (4) boosts magnesium absorption; (5) reduces levels of inflammatory biomarkers, such as high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor α (TNF-α); (6) raises levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase; (7) protects against pesticide-induced oxidative stress and heavy-metal toxicity; (8) improves the brains electrical activity, cognitive performance, and short-term memory for elders; (9) influences the formation and activity of key biomolecules, such as S-adenosyl methionine (SAM-e) and nicotinamide adenine dinucleotide (NAD+); (10) has demonstrated preventive and therapeutic effects in a number of cancers, such as prostate, cervical, and lung cancers, and multiple and non-Hodgkin’s lymphoma; and (11) may help ameliorate the adverse effects of traditional chemotherapeutic agents. In none of the numerous studies conducted to date, however, do boron’s beneficial effects appear at intakes > 3 mg/d. No estimated average requirements (EARs) or dietary reference intakes (DRIs) have been set for boron—only an upper intake level (UL) of 20 mg/d for individuals aged ≥ 18 y. The absence of studies showing harm in conjunction with the substantial number of articles showing benefits support the consideration of boron supplementation of 3 mg/d for any individual who is consuming a diet lacking in fruits and vegetables or who is at risk for or has osteopenia; osteoporosis; osteoarthritis (OA); or breast, prostate, or lung cancer.

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

I take 9 mg daily

Kaliber
Kaliber in reply to George71

I’ve been to the big boron mine here off interstate 15 ... toured the museum , took pictures with the mule team and giant tire etc. I can still remember the 20 mule team borax commercials as a little kid when it was a laundry soap and general cleaner in every household. Boron must be the jack of all trades. I take about 30 supplements every morning , pills ... less actual supplements, some multi’s might have boron in them , I’ll check . Thanks for the info

💪💪💪👍👍👍

George71
George71 in reply to Kaliber

Thats neat I bet it is huge -- I think that is one of the largest boron mines in the world ? ?

There is a lot of research on borons effect of PCa -- a double barrel benefit for us.

Boron supplementation inhibits the growth and local expression of IGF-1 in human prostate adenocarcinoma (LNCaP) tumors in nude mice

Maria T Gallardo-Williams 1 , Robert E Chapin, Paula E King, Glenda J Moser, Thomas L Goldsworthy, James P Morrison, Robert R Maronpot

Affiliations

PMID: 14713551 DOI: 10.1080/01926230490260899

Abstract

Prostate-specific antigen (PSA) is a serine protease and one of the most abundant proteins secreted by the human prostate epithelium. PSA is used as a well-established marker of prostate cancer. The involvement of PSA in several early events leading to the development of malignant prostate tumors has made it a target for prevention and intervention. It is thought that PSA cleaves insulin-like growth factor binding protein-3 (IGFBP-3), providing increased local levels of IGF-1, leading to tumor growth. Separately, there are data that suggest an enzymatic regulatory role for dietary boron, which is a serine protease inhibitor. In this study we have addressed the use of boric acid as a PSA inhibitor in an animal study. We have previously reported that low concentrations (6 ug/mL) of boric acid can partially inhibit the proteolytic activity of purified PSA towards a synthetic fluorogenic substrate. Also, by Western blot we have followed the degradation of fibronectin by enzymatically active PSA and have found significant inhibition in the presence of boric acid. We proposed that dietary supplementation with boric acid would inhibit PSA and reduce the development and proliferation of prostate carcinomas in an animal model. We tested this hypothesis using nude mice implanted subcutaneously with LNCaP cells in Matrigel. Two groups (10 animals/group) were dosed with boric acid solutions (1.7, 9.0 mgB/kg/day) by gavage. Control group received only water. Tumor sizes were measured weekly for 8 weeks. Serum PSA and IGF-1 levels were determined at terminal sacrifice. The size of tumors was decreased in mice exposed to the low and high dose of boric acid by 38% and 25%, respectively. Serum PSA levels decreased by 88.6% and 86.4%, respectively, as compared to the control group. There were morphological differences between the tumors in control and boron-dosed animals, including a significantly lower incidence of mitotic figures in the boron-supplemented groups. Circulating IGF-1 levels were not different among groups, though expression of IGF-1 in the tumors was markedly reduced by boron treatment, which we have shown by immunohistochemistry. These data indicate that low-level dietary boron supplementation reduced tumor size and content of a tumor trophic factor, IGF-1. This promising model is being evaluated in further studies.

here is another:

Dietary boron intake and prostate cancer risk

Yan Cui 1 , Meiko I Winton, Zuo-Feng Zhang, Charlene Rainey, James Marshall, Jean B De Kernion, Curtis D Eckhert

Affiliations

PMID: 15010890

Abstract

Boron affects human steroid hormone levels. Circulating testosterone and estradiol levels have been proposed to modify prostate cancer risk. However, the association between dietary boron intake and the risk of prostate cancer has not been evaluated by any epidemiological study. We explored the association between dietary boron intake and the risk of prostate cancer in the USA. Our analysis was based on data from the third National Health and Nutrition Examination Survey (NHANES III). Cross-sectional case-control study design was employed by comparing boron intake of 95 prostate cancer cases with that of 8,720 male controls. After controlling for age, race, education, smoking, body mass index, dietary caloric intake, and alcohol consumption, increased dietary boron intake was associated with a decreased risk of prostate cancer with a dose-response pattern. The adjusted odds ratio was 0.46 (95% confidence interval: 0.21-0.98) for the highest quartile of boron intake comparing to the lowest quartile (P for trend = 0.0525). The observed association should be interpreted with caution because of the small case sample size and the nature of the cross-sectional study design, but deserve further investigation.

cesces
cesces in reply to Kaliber

Hmmm

I'm sort of lucky. The metformin doesn't give me gi problems.

Kaliber
Kaliber in reply to cesces

Check out my reply to George71 for detailed info

💪💪💪✌️✌️✌️

cesces
cesces in reply to Kaliber

Where is that?

Kaliber
Kaliber in reply to cesces

The boron mine is located at Boron , Ca ...off highway 58. There is a boron museum in Boron and a great one at the mine. They have some great stuff inside, and a giant tire off a giant earth mover and a full size replica of a 20 mule team. There is a big factory in part of the pit where they make a lot of boron and borax related products. It’s kewl out there in the desolate nothingness. 58 is the big connector to 15 to Vegas.

dockam
dockam in reply to Kaliber

My dental office is in Tehachapi, and I have patients who work down there. It's about 40 miles going up the 58 westward

Randy

Kaliber
Kaliber in reply to dockam

Tehachapi ..... I’ve spent 100s of hours with truckloads of Scientific gear investigating the Tehachapi underground complex on Sand Hill Valley Road and the back end of Caliente. If you aren’t familiar with it, you can Google “ Tehachapi covert underground complex “ for more info. I could write a book on it yayahahahaya yayahahahaya. I’ve also examined the nearby super secret Tejon ranch radar test range where stealth aircraft and much more are tested. Stirred up a hornets nest there once and had three big black suburbans with porcupine antennas chasing me and my crew yayahahahaya trucks can have stealth too . Great fun trying to get a peek at what my tax dollars are up to.

Kaliber
Kaliber in reply to cesces

Lower doses don’t bother me as well, guess I hit my threshold or something

jmurgia
jmurgia in reply to Kaliber

Since your A1C is looking much better, would you consider backing off a bit on the metformin? Those side effects seem pretty severe to me. They may not be doing your digestive tract any good.

Joe

Kaliber
Kaliber in reply to jmurgia

That’s exactly right jmurgia .. I can cut back to 1500mg and the nastiness backs off considerably. Taking my A1C down made dramatic differences in healing that gaping hole on my forehead now ... nearly there . I talked with my medical team about the side effects ... but they told me getting that wound healed was of prime importance.... there had been three surgeries there and it went awful sideways. Told me to hit my opiates harder if needed , they would contribute to the “ plugging “ and settling power of the Imodium and make my discomfort more manageable too. At least until that hole healed.

So now I alternate days of 2000mg and 1500mg and the “ sickness - nausea “ has cleared up considerably and the diarrhea has backed off a lot too ...not gone but way better. Like you said , that stuff was probably trashing my digestive tract ...

It’s always something isn’t it ... medical whack-a-mole yayahahahaya

Thank you for your contribution brother, I appreciate it.

Peace 🦋🌸🌈🌼🌻🌵❤️

jmurgia
jmurgia in reply to Kaliber

Glad to hear you are doing better.

Kaliber
Kaliber in reply to jmurgia

You get so caught up in the PCa croakadosis thing that you don’t even hardly notice or give due credit to some little bleeding b.s. hole that pops up on your forehead, then “ boy howdy “ that turns into a monster just as dangerous as your body filled with PCa. It’s taken almost three years , multiple treatments and three surgeries to deal with that one little spot .... and still no guarantee . Yayahahahaya yayahahahaya. Still .... like you said, right this moment I am doing better ( than before ) ... looks like I got a handle on cancer #2 , I’m managing my PCa and able to stay comfortable enough ( good pain meds ) and have my fantastic caregiver / wifey right here by my side ... right here - right now , this Sunday morning watching football .... I very much appreciate that life is good in the moment ... I’m savoring it to the max ... you really appreciate life when it’s so precious.

I hope your day is going equally well and appreciative brother 💪💪💪✌️✌️✌️❤️❤️

SPEEDYX
SPEEDYX in reply to Kaliber

Skin care beauty is a never ending process...I can only imagine the improvement since your last photo!!

Kaliber
Kaliber in reply to SPEEDYX

Yayahahahaya yayahahahaya. ... did you see that one. yayahahahaya that was right after my 2nd or 3rd surgery ..I forget which ...they both looked that bad . That’s funny brother and yes I kinda look rather normal now compared to that yayahahahaya. Big scar is all ... Thank’ee brother , funny post. 😂😂😂❤️🌵🌵🦋❤️❤️

SPEEDYX
SPEEDYX in reply to Kaliber

I forget myself... Man Made Monster 😂....your an inspiration

There was some other research I saw on the internet about the combination of metformin, aspirin and stations reducing lung cancer.

For what it's worth.

It was peer reviewed research. I think out of Japan.

Another one bites the dust.

Break60
Break60 in reply to Tall_Allen

Based on this I’m going to stop taking my 1000 mg daily.

Break60
Break60 in reply to Tall_Allen

Have any benefits been found from dutasteride or celecoxib?

"In the assessment of the primary outcome, patients receiving metformin had a longer time to castration-resistant disease (median 29 months, 95% confidence interval 25 to 33) than those randomized to placebo (20 months, 95% confidence interval 16 to 24, p=0.01). This effect was most pronounced in men with high-risk localized disease and node-positive disease, marginal in those with low volume metastatic disease, and there was no benefit in those with high volume metastatic disease. There were no statistically significant differences in overall survival or PSA response rate."

That seems internally inconsistent?

No for dutasteride , They tried to see if it would extend the time on intermittent ADT -- it didn't.

Celecoxib only when combined with Zometa in metastatic men.

Break60
Break60 in reply to Tall_Allen

TA

What was the reason for using zometa?

Tall_Allen
Tall_Allen in reply to Break60

It preserves bone density in men using ADT and prevents fractures and spinal compression. There was some early suggestion that it might even slow down prostate cancer that had metastasized to bone. So there was a large scale trial as part of the STAMPEDE trials in the UK. It was found that it did not have any anti-cancer activity on its own, but it did when combined with celecoxib. The combination increased survival by 22%.

Break60
Break60 in reply to Tall_Allen

TA

Thanks. I’ve been using estradiol patches since 2/19 which are much easier on the bones and everything else except man boobs than lhrha like Lupron. No recurrence since then.

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