Metformin

[chocolatelover_123]

google.ca/amp/s/www.physici...

I read this article and it has me questioning on whether this is accurate or not.

Anyone here on metformin? How has it been for you?

Also, another question, what is free survival?

[tango65]

This is other recent article showing that metformin does not offer an advantage when use without statins:

sci-hub.tw/https://onlineli...

[snoraste in reply to tango65]

One of the better ones I've seen in these type of studies. I wasn't sure about the term "potency" in Table 3. Not defined in the text. I just sent them an email to ask. We'll see if they respond.

[Tall_Allen]

Yes, it's true. Metformin does not improve survival over docetaxel alone:

urotoday.com/conference-hig...

When added to ADT, it didn't reduce PSA more than a placebo in recurrent men in this small randomized trial:

ascopubs.org/doi/10.1200/JC...

It also didn't affect the risk of metabolic syndrome.

Progression-free survival means the amount of time that the men survived without any indication that their cancer was progressing. Indicators of progression may include higher PSA, more metastases on a scan, or death from prostate cancer.

[chocolatelover_123 in reply to Tall_Allen]

Can you have Metformin along with zytiga?

[Tall_Allen in reply to chocolatelover_123]

If you are diabetic, there are no known interactions that I'm aware of between metformin and Zytiga, so you can continue to take both safely.

[Tall_Allen in reply to Tall_Allen]

This small randomized trial also found no effect for metformin when added to Casodex in recurrent men:

meetinglibrary.asco.org/rec...

[novatimo]

This may have some relevance to your question.

careoncology.com/the-coc-pr...

[kapakahi]

I've been taking a statin for about 10-12 years because of high cholesterol, and metformin for about 6 years because of pre-diabetes. During this time my cholesterol normalized and I haven't had a heart attack or stroke, and I haven't progressed to full diabetes.

I've had prostate cancer for almost 12 years, at it comes and goes of its own accord regardless of what medication or supplement I'm taking, including statins and metformin and god knows what else. However, the cancer has never metastacized, so there's that, but that was true before I was taking metformin as well as since.

[VictoryPC in reply to kapakahi]

Great reply.

[kaptank]

I have taken metformin for more than 10 years on the reasoning that control of sugar and insulin is central to managing PCa. I cannot report any short term effect, but long term there is a certain evolving "indolence" in my cancer. This may have many reasons unrelated. It's one of those "why not do it" things.

[2dee]

I took Metformin for some years for another reason BUT it did nothing that I can judge to stop me from developing PCa.

2Dee

[GeorgesCalvez]

I take two times 500mg of metformin per day, at this level it seems to have some effect on my blood sugar but no episodes of diarrhoea.

However I do not have advanced prostate cancer, I have had a prostatectomy, radiation and ADT for 19 months, I currently have a PSA level of below the limit of detection.

Maybe having my avorstatin, irbesartan, metformin cocktail floating around will stop any residual PCa cells from getting off their backsides and doing something?

[EdBar]

I’ve been taking metformin for nearly 6 years, together with ADT, I started soon after dx per Snuffy Myers. I’ve not had a problem, kept my weight at a normal BMI and my PSA is undetectable. I take 1000 mg twice a day. Metformin is free when I get my script filled at Publix supermarkets. Snuffy has a few videos on Metformin on YouTube.

Ed

[6357axbz in reply to EdBar]

Thanks Ed. I just read your history with PCa. Impressive!

[Break60]

I’ve been taking metformin, rosuvastatin , dutasteride and celecoxib for many years. For the past year I’ve been using estradiol patches instead of an lhrh agonist. My “stage IV “ PCa is in remission. PSA <.1, T 3.0

[EdBar in reply to Break60]

What dose of estradiol are you using? I’ve also been using estradiol for several years now.

Ed

[Break60 in reply to EdBar]

Hi Ed

I’m using (3) .1 mg patches weekly. Sandoz brand.

[EdBar in reply to Break60]

I’m also still taking dutasteride and celecoxib. I use 2 patches a week. And I’m still on Lupron, but considering a holiday, just not sure I want to take that plunge. I was able to stop Xtandi a few months ago.

[VictoryPC in reply to Break60]

Great Info.

[carbide]

I have Type 2 diabetes & use Metformin.

On Eligard, Zytiga.

I take your article as saying Metformin has zero effect per cancer drugs.

[MateoBeach]

A dissenting opinion: This study showed a non-statistically significant trend favoring the metformin plus docetaxel arm vs. docetaxel alone. With 50 patients in the metformin arm and 49 without, this means that the differences in outcome measures could have been due to chance variation (distribution) within the populations studied.

The 24.2 months of Overall Survival with metformin vs. 19.7 months without is "clinically significant" (an important difference to those patients), even though the study lacked the statistical power (a high enough number of patients, etc.) to show that it was not due to chance variation alone.

As we know, "the lack of evidence of benefit is not evidence of no benefit" is applicable here IMO.

And the difference in rates of diarrhea were also not statistically significant either. It is known that metformin often causes diarrhea when it is first started but this usually abates and disappears within a few weeks for most people.

It is not surprising to me given that metformin's metabolic benefits that effect prostate cancer on multiple pathways, (apoptosis being just one) did not make a large difference in potentiating docetaxel's mechanism of cell death in prostate cancer. Though 4.5 months longer survival is not something I would "leave on the table" while undergoing chemo.

And this study does not address any possible benefits that might or might not accrue to those advanced PCA patients who take metformin longer term during their survival journey, rather than just while undergoing a course of docetaxel chemotherapy.

For a broader perspective of the evidence on metformin in prostate cancer this review in Nature is worth a read to make an informed decision:

nature.com/articles/s41598-...

"The effect of metformin therapy on incidence and prognosis in prostate cancer: A systematic review and meta-analysis"

[pjoshea13]

You asked: "what is free survival"

"Progression free survival with metformin was a median of 7.4 months; with placebo, it was 5.6 months.

"Overall survival was a median of 24.6 months if the patients were on metformin and a median of 19.6 months if the patients were on placebo."

"Progression free survival" depends on their definition of PCa "progression". There was a 32% advantage, even though that was only 1.8 months.

"Overall survival" means from death for any reason. I think that the extra 5 months (25%) shouldn't be dismissed.

However the disappointment was that 66% of patients treated with metformin plus docetaxel-prednisone achieved the primary endpoint of ≥50% decrease in PSA level versus 63% of patients treated with docetaxel-prednisone plus placebo - & this was a non-significant finding.

***

"TAXOMET is a phase II prospective multicenter randomized controlled trial. Non-diabetic mCRPC patients were assigned 1:1 to receive docetaxel 75 mg/m2 every 21 days plus prednisone 5 mg twice a day and either metformin 850 mg twice a day (arm A) or placebo (arm B), for up to 10 cycles. The primary endpoint was PSA response rate (≥50% decrease). Main secondary endpoints included objective response rate (ORR, according to RECIST v1.1), clinical and biological progression-free survival (PFS), overall survival (OS), toxicity and quality of life (QoL)." [1]

-Patrick

[1] urotoday.com/conference-hig...

[VictoryPC in reply to pjoshea13]

Great Article.

[Sxrxrnr1]

Have been on 1,000 mg Metformin for a number of years, along with Zocor

Only problem I have had is that all my medical records from any Physician or institution that I have consulted with are plastered that I also have Diabetes.

They have all refused any responsibility for correcting this. I am at times asked how am I treating my Diabetes. 🤪

[snoraste]

From the same paper comes a long disclaimer:

"This could suggest that either metformin is not clinically active for patients with CRPC, or that docetaxel may not be the right partner drug to be used in combination with metformin, or that the CRPC setting may not be the right disease state. The authors also suggested that perhaps if metformin had been continued at progression instead of discontinued at the same time as chemotherapy, this may have made an effect as the benefits may be more long term."

Small sample size definitely increases chances of type II error, but I hope the authors did the math to account for that (I could not find any reference to it).

[tonmead]

I am in the UK, on the stampede trial, arm K. Had my 6 docetaxel infusions in jan 2017, also given metformin as part of trial (2x850mg per day) PSA reduced from 1096 to 0.08. My last blood draw showed an increase to 0.14. Due another blood test next week, obviously hoping for a reversal in this increase. Stampede trial has issued no results on the Metformin trial, as far as I know, so I dont know how big a part, if any, Metformin played in my current good condition.

[jfoesq]

I am not a scientist nor a statistician, but form what I read in the article and all the additional comments I read on this platform about it: Metamorfin doesn’t appear to cause harm; and might still be proven to be effective when and if other studies are done