Metformin: Taking away the candy for cancer?

[1rarebird]

We've been discussing sugars and their roles in promoting breast cancer. Here is a possible drug that could help in that regard.

http://www.peerview-institute.org/ne..._uids=20656475

Eur J Cancer. 2010 Jul 23. [Epub ahead of print]
Metformin: Taking away the candy for cancer?

Jalving M, Gietema JA, Lefrandt JD, Jong SD, Reyners AK, Gans RO, Vries EG.
Department of Medical Oncology, University Medical Centre Groningen, The Netherlands; Department of Internal Medicine, University Medical Centre Groningen, The Netherlands.
Abstract

Metformin is widely used in the treatment of diabetes mellitus type 2 where it reduces insulin resistance and diabetes-related morbidity and mortality. Population-based studies show that metformin treatment is associated with a dose-dependent reduction in cancer risk. The metformin treatment also increases complete pathological tumour response rates following neoadjuvant chemotherapy for breast cancer, suggesting a potential role as an anti-cancer drug. Diabetes mellitus type 2 is associated with insulin resistance, elevated insulin levels and an increased risk of cancer and cancer-related mortality. This increased risk may be explained by activation of the insulin- and insulin-like growth factor (IGF) signalling pathways and increased signalling through the oestrogen receptor. Reversal of these processes through reduction of insulin resistance by the oral anti-diabetic drug metformin is an attractive anti-cancer strategy. Metformin is an activator of AMP-activated protein kinase (AMPK) which inhibits protein synthesis and gluconeogenesis during cellular stress. The main downstream effect of AMPK activation is the inhibition of mammalian target of rapamycin (mTOR), a downstream effector of growth factor signalling. mTOR is frequently activated in malignant cells and is associated with resistance to anticancer drugs. Furthermore, metformin can induce cell cycle arrest and apoptosis and can reduce growth factor signalling. This review discusses the role of diabetes mellitus type 2 and insulin resistance in carcinogenesis, the preclinical rationale and potential mechanisms of metformin's anti-cancer effect and the current and future clinical developments of metformin as a novel anti-cancer drug.

bird

[Jackie07]

I wondered if a retroactive study can be done to see if diabetes patients who take metformin have lower [breast] cancer rate.

[ElaineM]

Interesting concept !!

[Rich66]

More on Metformin:
http://her2support.org/vbulletin/showthread.php?t=39740

[1rarebird]

As the link Rich provided to the thread last year on Metformin indicates, this drug and its effect on insulin and probably insulin-like growth factor and the ER has not just recently been considered by some researchers as a promising therapeutic for breast cancer. Trials in Canada are recruiting at present to learn more about this possibility.

Given the well known and moderately mild side effects profile that Metformin has exhibited during its long history of clinical use to treat diabetes, I wonder if there are any oncologists using it at present in off-label fashion with their breast cancer patients. It would seem to me that the risks are low and the benefit potential is high---well, at least as high as the known benefits of other drugs like Tamoxifen which show ER control in the range of 40 to 50% which is in the same ballpark of benefit demonstrated in the retrospective studies on Metformin.

bird

[Rich66]

Mom's getting it off-label, extended release tab. I know there's one other poster here who started it for diabetic-like reasons but continues off-label.
The thing I have to find out is what makes sense regarding PET scans. It's been historically contraindicated because it has been thought to interfere with cancer's metabolism of the injected glucose. But...that's part of why it is thought to be helpful. So..one would want to see that it's working, right?

[jml]

I am on Metformin, prescribed originally for Insulin Resistance after my 1st year of treatment, when I was experiencing symptoms. Those have all resolved, though I continue on Metformin off label.
My onc used to question whether or not I should continue on it, but in light of the most recent research re: Metformin & BC, she supports my continued us.
Also, it's very important that anyone taking Metformin d/c use 36 hrs before and after ANY scans - PET or CT. I've even noticed that they're now asking patients to sign a form consenting NOT to used there meds within this range of time. My understanding is the the combo of the contrast & drug is very hard on kidneys.
I wonder how many oncs out there would be willing to start their onc patients on Metformin off-label. It's still such a new concept. From my own experience I'm constantly explaining to folks that I'm NOT diabetic, but WAS insulin resistant, but NOW take the drug for BC...most people just glaze over when I start to explain.
I do feel fortunate to have access to the drug.

[AlaskaAngel]

Last September in the nutrition forum I was interested in metformin also as a way of dealing with insulin resistance:

http://her2support.org/vbulletin/sho...10395#poststop

Other than breast cancer I have no other health problems, but what seems to be insulin resistance developed for me as a result of breast cancer treatment.

The two largest groups of breast cancer patients are the early stage breast cancer group, and the group over 50 years of age (mostly composed of the same patients). I've raised the question about whether applying current therapies for hormone receptor positive, early stage breast cancer patients who are least at risk for recurrence may actually be resulting in a greater net risk for recurrence through weight gain by insulin resistance.

It would be very helpful if metformin does have some general additional usefulness in preventing recurrence.

I saw an endocrinologist and asked about metformin in February, and the endocrinologist is willing to consider it. At present I am dieting and exercising and keeping a diary, and am planning to bring that information to my next appointment for further discussion about possible use of metformin.

I would like to have a better understanding of the action of metformin and metabolism.

A.A.

[AlaskaAngel]

Actively recruiting clinical trial for use of metformin for early stage bc:

http://clinicaltrials.gov/ct2/show/N...tformin&rank=2

This is for those diagnosed who have undergone definitive surgical treatment within the past 12 months. (see additional requirements also)

[Rich66]

Since my mom is thought to be allergic to contrast, she gets PET/CT w/o contrast. In which case, it seems like the suggestion is to not take Metformin the morning of the PET.


LINK

Persons with diabetes who are taking metformin (some of the brand names include Glucophage®, Glucovance®, or Metaglip®) must STOP the medication on the day of the exam and 48 hours after receiving intravenous contrast. The combination of the drug with the contrast material that is used for CT scans could cause serious side effects. Be certain to discuss this with your physician.


LINK

Oral Hypoglycemic Agents

• The day before the PET scan Take your usual oral hypoglycemic agents and eat regular meals the day before the PET scan.
• Fast for 12 hours.
• On the morning of the PET scan Do not take your oral hypoglycemic agents.

After the PET scan is done For Metformin (Glucophage, Glucophage XR, Fortamet, Glumetza, Riomet): The PET scan technologist will tell you how and when to resume taking Metformin after the PET scan. If a contrast CT scan is done, do not take Metformin for 48 hours and do not resume taking it before your renal function has been tested and shown to be normal. You will receive instructions about this on the day of your scan.
For oral hypoglycemic agents other than Metformin (see above for brand names): Take your usual oral diabetes medicines with lunch. After this, return to your usual doses.