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Using metformin?

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123Donna View Drop Down
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Sep 25 2011 at 10:32pm
QUOTE=Grateful for today]Hi Aloha Girl Warrior,

Putting a note here hoping some Senior and other members might comment.   I don't know the answer......and don't know IF the question is worth bringing up with your MD's. It has to do with studies
re: metformin given at the same time as chemo (specifically doxorubicin....adriamycin).   
THINK this might be too unproven by clinical trials.
Let's see what others think.
Then you can choose to review with your MD or not.
Really hope this is not too confusing. Sending as you asked for comments and were considering metformin.   

From: Molecular Cancer THerapeutics May 2010. Vol 9. no.5   1092-1099
Metformin in Cancer Therapy: A New Perspective for an Old Antidiabetic Drug?
Table 1.
Summary of epidemiological in vivo and in vitro studies done with metformin in different cancers
Type of cancer     Conclusions     Epidemiological studies     Preclinical studies     In vitro studies
(apologies the numbers did carryover into the correct columns re: epi/preclinical/in vitor studies but
this gives you an idea of what's in the article) (see article)
Breast     Higher response to chemotherapy in patients treated with a combination of metformin and chemotherapy     (67)          
Metformin inhibits the development of mammary tumors in HER-2/neu mice          (40)     
Metformin growth inhibition is mediated by AMPK               (22)
Metformin inhibits translation initiation in a LKB1/AMPK–dependent way               (21)
Metformin blocks cell cycle progression at S phase and induces apoptosis in triple-negative breast cancer cells          (35)     (35)
Human genome array of metformin-responsive genes in MCF-7, SKBR3, and MCF-7/HER2               (64)
Metformin induces cell cycle arrest in MCF-7, BT-474, and SKBR-3               (34)
Metformin restores lapatinib sensitivity in MCF-7/HER2 LapR               (65)
Metformin suppresses erbB-2 expression via inhibition of mTOR in SKBR3 and MCF-7/HER2               (37)
Metformin induces cell cycle arrest and cyclin D1 inhibition in MDA-MB-231 cells               (32)
Metformin inhibits MDA-MB-435 cancer cell growth but promotes angiogenesis and tumor growth in vivo          (43)     (43)
Metformin selectively kills cancer stem cells at low doses (0.1-0.3 mmol/L). Synergistic effect of doxorubicin and metformin          (33)     (33)


Article:
from: Cancer Research. Oct 1,2009    69   7507-11.
"Metformin Selectively Targets Cancer Stem Cells, and Acts Together with Chemotherapy to Block Tumor Growth and Prolong Remission"
Heather A. Hirsch1, Dimitrios Iliopoulos1, Philip N. Tsichlis2, and Kevin Struhl
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and 2Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts
Requests for reprints:
Kevin Struhl, Harvard University, 240 Longwood Avenue, Boston, MA 02115. Phone: 617-432-2104; Fax: 617-432-2529; E-mail: kevin@hms.harvard.edu.
Abstract

The cancer stem cell HYPOTHESIS suggests that, unlike most cancer cells within a tumor, cancer stem cells resist chemotherapeutic drugs and can regenerate the various cell types in the tumor, thereby causing relapse of the disease. Thus, drugs that selectively target cancer stem cells offer great promise for cancer treatment, particularly in combination with chemotherapy. Here, we show that low doses of metformin, a standard drug for diabetes, inhibits cellular transformation and selectively kills cancer stem cells in four genetically different types of breast cancer. The combination of metformin and a well-defined chemotherapeutic agent, doxorubicin, kills both cancer stem cells and non–stem cancer cells in culture. Furthermore, this combinatorial therapy reduces tumor mass and prevents relapse much more effectively than either drug alone in a xenograft mouse model. Mice seem to remain tumor-free for at least 2 months after combinatorial therapy with metformin and doxorubicin is ended. These results provide further evidence supporting the cancer stem cell hypothesis, and they provide a rationale and experimental basis for using the combination of metformin and chemotherapeutic drugs to improve treatment of patients with breast (and possibly other) cancers. [Cancer Res 2009;69(19):7507–11]

Some thoughts:
The nurse practitioner working with my medical oncologist said: Regarding chemotherapy, remember
all side effects are possibilities and not probabilities.
It has been suggested that when good friends/relatives asks: What can I do to help?......Have some
specific things that would be helpful for you.   Bring a meal over the night of chemo days. Help out with
rides for the children for their activities/school etc.   Think one of the best ideas I have heard: delegate
one of your best friends/relatives to be "your volunteer coordinator". Then, every time some one says:
How can I help? You can say: I'll give your name and phone/e-mail to my volunteer coordinator. That
way you let that one person know what you need and that one person sets up the help ( or some system
like this that would work for you and your family).

With caring and positive thoughts that your treatment plan makes you NED (no evidence of disease).

Grateful for today.
Judy
[/QUOTE]

Judy,

Interesting article you posted on Metformin and chemo on breast cancer stem cells.  Thanks.  Here's the link:

http://cancerres.aacrjournals.org/content/69/19/7507.short





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Post Options Post Options   Thanks (0) Thanks(0)   Quote Craig76 Quote  Post ReplyReply Direct Link To This Post Posted: Sep 25 2011 at 11:23pm
Any news on how well these trials are going?
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Sep 27 2011 at 8:34am
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Sep 28 2011 at 8:49am
Craig,

Maybe we'll hear more about these metformin trials from the ASCO conference in December.

Here's another study looking at insulin and tnbc: 

Test Could Detect Breast Cancers Earlier in Young, High-risk African-American Women


http://www.aacr.org/home/public--media/aacr-in-the-news.aspx?d=2457
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
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Post Options Post Options   Thanks (0) Thanks(0)   Quote LauraT Quote  Post ReplyReply Direct Link To This Post Posted: Sep 28 2011 at 3:59pm
Hi All - just got back from my appointment with the endocrinologist. He had no problems with my taking metformin and gave me a prescription! They gave me a blood sugar testing kit and told me to test my blood sugar only if I felt faint, weak, etc. They also want to follow my kidney function tests closely. According to him, they prescribe it "off-label" quite a bit for various reasons. I hope it helps in the fight against this wretched monster!

Laura
DX 10/09 @44, Stage I IDC tnbc, DCIS other side, Neoadjuvant TCx4, Bilateral Mastectomy w/Recon 1/10, 1.2cm 0/7 Nodes, 5/11 Mets to Lungs/Lymph Nodes, Avastin/Taxol, 10/11 Bone Mets, Xgeva
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post Posted: Sep 28 2011 at 5:23pm
Craig: RE: status of metformin vs placebo trial MA 32.
             Don't know actual status.
             Per:   NCIC clinical trial group website: "looks" like trial started 6/2010.
             Per article:
               Evaluation of metformin in early breast cancer: a modification of the traditional paradigm for
                   clinical testing of anti-cancer agents. Pamela J. Goodwin (et al)
               Breast Cancer Res Treat (2011) 126:215-220.
                      "The trial is powered to identify a hazard ratio 0.76 in the metformin arm, with 80%          
                         power and a type 1 error of 0.05 (2 tail) allowing for two interim analyses."
                         Gave whole sentence as THINK it means 2 interim analyses before study ends.
                         (Question if this would mean an interim analyses (and ? what analyses) in 2012.)
                         "The primary efficacy analysis is anticipated 6 years after the first subject is enrolled."
                                (Question this means in 2016)
                         Info vague.......but thought I would share.

                        Craig, you put good posts on the forum.......thanks.


                      Grateful for today............Judy
                         
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Sep 28 2011 at 6:18pm
Laura,

You are doing everything to fight this monster.  Throw everything at it you can.  I admire your courage and strength.  Keep us posted as to any side effects you notice.

Donna
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Craig76 Quote  Post ReplyReply Direct Link To This Post Posted: Sep 29 2011 at 10:37am
Thanks for the info Judy.  Ugh...2016.  That is just way too long.  I would have liked to have seen how it did against late stage breast cancer.   We need more options for people with stage 3 and 4 cancers. 
 
Laura...I think that is awesome that you were approved to use this drug.  Good luck with it and please keep us posted! :)


Edited by Craig76 - Sep 29 2011 at 10:38am
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Post Options Post Options   Thanks (0) Thanks(0)   Quote KatieMarie Quote  Post ReplyReply Direct Link To This Post Posted: Oct 19 2011 at 8:27pm

Hi, just thought I'd post my experience with trying metformin off label.

Doc put me on 500mg twice a day.
 
I did great for about three months.  I lost 10 pounds right away, that was kinda nice, but not why I wanted to try it.  I think my pharmacist might have thought that was what I was trying, because when she gave me my first bottle, she said out of the blue the only way people are losing weight is because of diarrhea on it.  Well, I had been having trouble with that anyway and on the metformin it went away, so go figure.
 
After about three months, though, I had these things happen:
- got dizzy one evening, that night got a 103 fever, out of commission in bed for a day and a half and then had bad diarrhea one day
- got dizzy eating lunch maybe a week later and then had to lay down rest of day
- was sitting watching tv and surfing on laptop when my heart started fluttering.  Then I started to have a squeezing in my chest, it lasted less than 30 seconds.  Then I had pain in my left arm and my left arm went numb.  That was a fun night.  EMT's came and EKG was fine, did not go to ER
- doc ordered a heart work up with cardiologist, did an ultrasound, EKG and stress test, all fine
 
We are trying 250mg twice a day now.  Has been about a month and have not had any problems so far.
 
I still don't understand why I had all these problems, which are listed as all the things you are supposed to call your doc about while on metformin.  My bloodwork was all fine, including liver and kidney function.  Maybe it wasn't the metformin.
 
I have a lot of high hopes for metformin.  I have seen other posts that the 250mg might be sufficient, hoping that is the case.  Would have been nice if this could have been an easy, straightforward thing, but with TNBC, nothing is easy,  I should have known that!!
 
Anyway, just adding it to the information out there.  Appreciate all of you so much.
Katie
IDC dx 4/24/09, Age 40
Two surgeries, three tumors: 1.4cm,4mm,2mm; Ki67=75
Stage 1, no node involvement, clean margins
BRCA 1/2 negative,
Chemo: AC dose dense then Taxol dose dense, then rads
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post Posted: Oct 20 2011 at 12:27am
FYI:

There are over 150 current active metformin vs placebo clinical trial sites in the U.S.!!!!!!!!!!

For the past few weeks, I have been trying to find out where all the sites are listed.
On: www. clinicaltrials.gov   only the Canadian sites are listed.

After seeing the above post, decided to put some info on the forum...in case anyone is interested
and nearing the one year within diagnosis cut-off point for the clincial trial.

FINALLY spoke to someone today in Canada (NCIC ctg) who was not aware that the U.S. sites were not
showing up on the clnicaltrials.gov site. This person said they would get back to me tomorrow
if possible. He sent an email to the appropriate person in Canada (but it was the end of the business
day.)   Initially, I was going to wait for his reply. Then, was concerned some people might be nearing
the cut off date....thus, this post.
It's been an interesting few weeks. It started with a call to the clinical trials group in Canada......who
referred me to the U.S. NIH and NCI. The NIH and NCI keep referring me back to the other group.
Finally, spoke with someone at the National Library of Medicine who referred me back to Canada!!!
Fortunately, the man in Canada today was VERY eager to get the U.S. metformin vs placebo clinial
trials sites listed at clinicaltrials.gov.

In Canada:     NCIC-CTG-MA.32
In U.S.:            NCT: 01101438
(maybe by the time some of you read this the clinicaltrials.gov site will show both the U.S. sites
and not just the Canadian sites for NCT: 01101438)

NCT:01101438 Clinical Trial
Phase III Trial of Metformin versus Placebo in Early-Stage Breast Cancer
Definitely open at:
     Dana Farber Cancer Institute                      Boston, MA
     Vanderbilt Cancer Center                             Nashville, TN
     Indiana University Simon Cancer Center    Indianapolis, IN

If one googles:
"Phase III Trial of Metformin versus Placebo in Early-Stage Breast Cancer"
individual sites will come up which appear to have the metformin vs placebo clinical trial.
I did not verify but more then likely the following do have the trial:
CA:    Norris Comprehensive Cancer Center    Los Angeles, CA
KY:    Central Baptist Hospital   Lexington, Kentucky
N.H.: Concord Hospital     Concord, N.H.
N.M.: New Mexico Cancer Care Alliance   505-272-7813
N.Y.:   Northern Westchester, N.Y.
N.Y.    Mt Sinai Medical Center N.Y. N.Y.
Ohio: Ohio State Cancer Center, Columbus, Ohio 614-293-5066
Ohio: Metrohealth Medical Center.   Case Western Reserve University.
PA:      Fox Case. Philadelphia, PA
Utah: Huntsman Cancer Institute. Salt Lake City, Utah.
VA:      Martha Jefferson   Charlottsville, VA
WA:     Swedish Cancer Institute    Seattle, WA.
WA:     Seattle Cancer Care Alliance.   Seattle, WA
D.C.:   Sibley Memorial Hospital   Washington, D.C.
Members of the Eastern Cooperative Oncology Group.
Member of the Southern Cancer Control Consortium, Inc 336-777-3036
There are a few other sites listed when one googles "Phase III Trial of Metformin versus Placebo in Early-Stage Breast Cancer "
(You will need to google site to get phone number for the cancer centers above. Did list just a
few phone numbers)

Will post any info on the forum once I hear back.

If anyone knows of other definite sites having this trial and they are not listed above, please post.
Again, hopefully VERY SOON the clinicaltrials.gov site will have ALL the U.S. sites with complete
addresses and phone numbers.

Grateful for today.........Judy
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post Posted: Oct 20 2011 at 12:55am
Addendum to above:
Members of the Southern Cancer Control Consortium, Inc    phone: 336-777-3036

SCCC Communities
Each community has a physician designated as the Community Leader and a research nurse/ clinical research associate appointed as the Study Coordinator. These two individuals coordinate and implement the NCI sponsored clinical trials that are best suited for their community.
To learn about clinical trial availability and ask general questions, call the site nearest you and contact the Study Coordinator/Contact Person listed at the top of each community. You can also refer your questions to our general email address: scccinfo@wfubmc.edu.
Asheville, NC
Cary, NC
Charleston, SC
Charlotte, NC - Carolinas Medical Center
Charlotte, NC - Presbyterian Hospital
Columbia, SC
Danville, VA - Danville Center of Radiation Oncology
Danville, VA - Danville Hematology/Oncology, Inc.
Florence, SC
Gastonia, NC
Goldsboro, NC - SMOC
Goldsboro, NC - Wayne Radiation Oncology
Greensboro, NC
Hendersonville, NC
High Point, NC
Kingsport, TN
Martinsville, VA
Pinehurst, NC
Raleigh, NC - Cancer Centers of NC
Savannah, GA
Statesville, NC
Winston-Salem, NC

Judy
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post Posted: Oct 20 2011 at 1:15am
Another addendum for those who may be close to being within one year of diagnosis.

Since there are reportedly (per Canada's National Cancer Institute) so many U.S. trial sites,
if you do not see a site near you, consider:
Call your usual cancer center and other surrounding cancer centers to see if they have the
metformin vs placebo trail. If none do, ask their clinical trial research person, if they know of the
nearest metformin vs placebo clinical trial.
In U.S.:    NCT: 01101438    Phase III Trial of Metformin versus Placebo in Early-Stage Breast Cancer

Judy
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Oct 20 2011 at 7:54am
Judy,

Thank you for all your research on this subject.  I looked at the site this morning and only the Canadian locations were listed.  Hopefully, they'll update this information soon.  

Maybe we'll hear more about Metformin at the December ASCO conference.  

Donna
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post Posted: Oct 20 2011 at 12:26pm
GOOD NEWS!!!!

Recieved an email this morning from the gentleman that I spoke with yesterday at the
NCIC CTG. (National Canadian Institute for Cancer: Clinical Trial Group)
He said their IT department is working on the issue.
He expects the U.S. metformin vs placebo clinical trials sites to be posted in the U.S. in
the next day or two.

Repeating from above posts of yesterday with only some site:
For those who may be close to being WITHIN ONE YEAR OF DIAGNOSIS:.
Since there are reportedly (per Canada's National Cancer Institute) so many U.S. trial sites,
if you do not see a site near you, consider:
Calling your usual cancer center and other surrounding cancer centers to see if they have the
metformin vs placebo trail. If none do, ask their clinical trial research person, if they know of the
nearest metformin vs placebo clinical trial.
In U.S.:    NCT: 01101438    Phase III Trial of Metformin versus Placebo in Early-Stage Breast Cancer


Grateful for today.............Judy
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Post Options Post Options   Thanks (0) Thanks(0)   Quote mikel Quote  Post ReplyReply Direct Link To This Post Posted: Oct 21 2011 at 9:22am
Hello,

I have just seen this info:

http://www.medscape.com/viewarticle/748480


Metformin Doesn't Help Survival in Triple-Negative Breast Cancer

NEW YORK (Reuters Health) Aug 23 - Metformin won't improve survival for diabetic women receiving adjuvant chemotherapy for triple-negative breast cancer, a new study suggests.

Observational studies have shown reductions in cancer incidence and cancer-specific mortality in diabetics who take metformin. Earlier this year, a Spanish research group reported that metformin suppresses the breast cancer marker CD24, but up to this point there's been very limited clinical data on metformin and breast cancer.

Whether metformin benefits patients with breast cancer is being examined now in a phase III trial by the National Cancer Institute of Canada Clinical Trials Group.

In the meantime, Dr. Ana M. Gonzalez-Angulo and colleagues from The University of Texas MD Anderson Cancer Center in Houston have used registry data to explore the issue.

They studied 1448 women enrolled in their Breast Cancer Management System database, looking at distant metastasis-free survival (DMFS), recurrence-free survival (RFS), and overall survival (OS). There were 63 diabetics on metformin, 67 not on metformin, and 1318 nondiabetics.

Each woman had been diagnosed and treated with surgery and adjuvant chemotherapy for triple receptor-negative breast cancer (i.e., negative for progesterone, estrogen, and HER-2 receptors) between 1995 and 2007. The median follow-up for survivors was 62 months (range, 1-176 months).

Estimated five-year DMFS did not differ significantly among the metformin (73%), no-metformin (66%), and no-diabetes (60%) groups, nor between the metformin group and the no-diabetes controls.

Estimated five-year RFS and OS rates were also similar: 65% and 67%, respectively, with metformin, 64% and 69% in diabetics not taking metformin, and 54% and 66% in controls.

Older age, T1 to T2 status, N0 status, and no lymphovascular invasion were independent predictors of better DMFS and RFS, whereas T3 to T4 status, N1 to N3 status, lymphovascular invasion, and higher nuclear grade predicted worse OS.

"The results of the current retrospective analysis suggest that metformin use during adjuvant therapy was not associated with improved survival outcomes in diabetic patients with triple receptor-negative breast cancer," the researchers conclude. "However, there was a trend toward a decrease in the risk of developing distant metastasis in diabetic patients receiving metformin compared with nondiabetic patients."

A review article published several months ago in the open-access journal BMC Medicine noted that the randomized metformin trial underway in Canada is not limited to diabetics. According to that article, by Ryan Dowling from the Ontario Cancer Institute and colleagues, the Canadian study (NCIC CTG MA.32) is comparing metformin to placebo in more than 3,500 women with early breast cancer.

Best regards,

Mikel
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Oct 21 2011 at 4:41pm
Thanks Mikel.

I found this article to talking about TNBC and metformin:

Duke Team IDs Warburg Effect and Linked Proteins as Possible Breast Cancer Predictor, Drug Target


http://www.genomeweb.com/proteomics/duke-team-ids-warburg-effect-and-linked-proteins-possible-breast-cancer-predicto
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (0) Thanks(0)   Quote TNinTN Quote  Post ReplyReply Direct Link To This Post Posted: Oct 21 2011 at 7:20pm
Thanks Mikel and Donna,
 
Susan is in the Metformin trial. She is also taking 5,000/day of Vitamin D and also takes Lexapro which I believe is an SSRI. Hopefully, one of them or all of them together will work.
 
Martin
Wife age 53@dx TN IDC Stage IIA 7/10; BRCA1&2 Neg; BROCA Neg; LN Neg; taxol+cisplatin+/-RAD001x12(clinical trial); lumpectomy 12/10;ACx4; 33 Rads complete 4/11; NED 5/5/11
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Post Options Post Options   Thanks (0) Thanks(0)   Quote blen9 Quote  Post ReplyReply Direct Link To This Post Posted: Oct 25 2011 at 1:16pm
Hi Everyone,
 
For those taking metformin 820 2x a day...are you having any side effects? I feel uneasy in my chest, get heart pulpitations at night, have to pee often, and get constant hot flashes and have zero energy. If anyone could share that would be helpful.
 
Thanks :)
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Post Options Post Options   Thanks (0) Thanks(0)   Quote cheeks Quote  Post ReplyReply Direct Link To This Post Posted: Oct 25 2011 at 1:48pm
blen9,

Is Metformin the only medication you are currently taking? I would call your pharmacist and doctor. I had some of those symptoms while on chemo but that doesn't mean it couldn't be the Metformin.

Blair


Edited by cheeks - Oct 25 2011 at 1:49pm
Lump found 11/08 @51
DX: 2/09 @52 TNBC
L. Mast. 3/26/09, SN-, BRCA-,
4.5 cm (post surgical)T2NOMO
Chemo: 4/09-10/09 Taxol x 12,
A/C x 4, No rad., No recon. NED 1/16
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Joined: Oct 26 2011
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Post Options Post Options   Thanks (0) Thanks(0)   Quote LivingLarge Quote  Post ReplyReply Direct Link To This Post Posted: Oct 26 2011 at 12:30pm
I took Metformin during chemo as one of the SE from chemo is my sugar levels went sky high.  My onc told me that there were trials going on using Metformin as he said there was an idea that since cancer feeds off sugar that if they lower sugar levels it will help slow the growth of cancer or prevent a recurrence.  After chemo I was taken off the drug since my sugar went back to normal.  Given the simple logic I would like to stay on it since I had no SE.  
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