Genomic Testing Results and Treatment for Recurrence

Cindy,

I too had my genomic testing done in January 2015. I was Stage 3 Grade 3 endometrioid adenocarcinoma.  Grade 3 has some
crossover with serous carcinoma. I metastasized to 34cm of new tumors two months after my surgery, right before I was to
start my Taxol/Carbo.

I believe the two drugs recommended for you were the same for me - Everolimus and Temsirolimus. I had a PIK3R1 mutation.
Both your mutation and mine are part of the PI3K/Akt/Mtor pathway, which is mutated in over 80% of all endometrial cancers.
This pathway controls insulin. Everolimus was recommended by my integrative oncologist but he also put me on metformin, and
I never had a need for the Everolimus.

I was put on the drug metformin after two chemo infusions of Taxol/Carbo. I had originally entered a trial at Sloan that added
metformin or a placebo to the Taxol/Carbo, but when I learned that it would address my insulin resistance (pre-diabetes) and high insulin
growth factor levels and has over seventeen anti-cancer properties, I knew I had to be on this drug. I removed myself from the trial
at Sloan (which runs till the end of 2019) and my integrative oncologist prescribed the drug for me.

Metformin inactivates the PI3K/Akt/Mtor pathway. Mine was activated through my PIK3R1 mutatation- if your pathway is activated
from the PIK3CA mutation, metformin could be an effective targeted treatment for you. It is the most prescribed drug in the world for
type 2 diabetes. TP53 is a tumor suppressor gene that is also tied to this pathway. If the F1 report says your gene is turned off,
metformin restores TP53 expression.  Metformin also inhibits the notch signalling pathway (notch 3).  I'd have to do some more research,
but I believe it also benefits SRC.  All these things are tied together.

Metformin also does what Avastin does. It inhibits VEGF and stops angiogenesis. But Metformin also kills cancer stem cells,
which is what causes cancer to recur. Avastin does not kill cancer stem cells. Avastin was also recommended by my integrative oncologist, but
since I had miraculous results with the metformin only, I never tried the Avastin. I was very concerned about the side effects of Avastin.
88% of my tumors vanished after one month on metformin and only 3 chemo infusions. Sloan couldn't explain the results.

I would highly suggest you start the metformin with your chemo- they won't tell me if I was getting the actual metformin for the first
two chemo infusions- but I was on the real drug for my remaining 4 infusions.  Just so you know, the medical literature says that if
you have a mutation on this PI3k/Mtor pathway, it makes you chemo resistant.  I believe this is what they were testing in the trial I
was in as the goal was to add the metformin to make the chemo work better (and they are measuring both your mutation and mine
as part of the trial). If you want the trial number, let me know.

I have been in complete remission since August 2015- my last and 6th chemo infusion was May 2015. I still had 2cm of tumors when
the chemo ended but they vanished as well  3 months later - I only took the metformin. (The only drugs I've been using since chemo
ended ismetformin and aspirin (2 low dose each day), but I do use 44 different supplements as well.

I would highly recommend you ask your doctor about getting on metformin as you begin the chemo. It is a miracle drug that seems
to help those with a certain cancer profile.

One last thing.  Metformin has also shown successful results for breast cancer, as 44% of breast cancer patients also have a mutation
on the PI3K/Akt/Mtor pathway and high insulin growth factor levels also drive breast cancer (believe it causes dense breasts, which I
also have).

Takingcontrol58

cindy0519 said:

Takingcontrol  - I was

Takingcontrol  - I was intitally diagnosed as Stage 3IIC1 USPC (Grade 3).  You are correct, the recommended drugs that were Everolimus and Temsirolimus, and most specifically my onco said chemo (Carbo/Taxol) with either Temsirolimus or Avastin were my choices.  The F1 report does indeed show TP53 "turned off" and says that this is common in agressive advanced cancers and 28% of endometrial carcinomas have this gene turned off.   I don't qualify for any trials as I was diagnosed with breast cancer in May 2016 and USPC in Sept. 2016 so that alone precludes me from trials.  

Our cases do seem similar in many ways but are also different in a many so while I am excited about your experience with Metformin it may not be the "magic pill" for me.  I will send my onco an email and ask about setting up time to discuss Metrformin though I anticipate that she will say that our differences make a difference If you have the trial number handy and can send it to me I would like to reference it in my message to my Onco.  It's odd that Metforim can be "magic pill" and yet there is no mention of it anywhere in the F1.  

Thanks for your response and for "speaking my language" (so to speak).  It's awesome to talk with someone that gets it!

 

Cindy,

The trial I was enrolled in was entitled "A Randomized Phase II/III Study of Paclitaxel/Carboplatin/Metformin (NSC#91485)
versus Paclitaxel/Carboplatin/Placebo as initial therapy for measurable Stage III or IVA, Stage IVB or Recurrent Endometrial
Cancer. NCT #02065687 (GOG286B).

The reason metformin is not on the Foundation One report is because metformin is not FDA approved for cancer. But
the industry first learned about its anti-cancer benefits in 2005. It can be prescribed off-label for you or if you are
pre-diabetic or diabetic or have high IGF-1, you should be on it anyway. It is also used to treat PCOS.

Remember, Avastin is being prescribed for you "off-label" as it is not FDA approved for endometrial cancer. So be sure
to bring that up if your doctor says metformin would have to be prescribed off label.  Avastin was actually pulled off the
market in 2010 because it was harming breast cancer patients. The risks were greater than the benefits.  I don't know why
it is being prescribed today.

I am very detail oriented.  You don't need to be in a trial to be on metformin.  It really bothered me that Sloan told my
husband that I had maybe 4-6 months to live yet put me in a trial with a drug that is generic and costs me $8/month- and
I had a marker and was a patient that would have benefited from the metformin (but the trial was random). They still
won't tell me if I was on the drug until the trial ends- 2019. I intend to be alive by then.  Sloan even called my integrative oncologist
unthical for putting me on the drug.  That made me very suspicious of their reaction. 

You may have to get the prescription from your internist. Most oncologists fight prescribing this drug. One hundred twenty million people
take this drug - it is considered one of the 100 most essential drugs in the world by the World Health Organization-it is safe, it works and
it is cheap. An article in pubmed.gov actually calls metformin a "magic" drug. It was first used in 1958 in Europe or Canada, I forget
which country. So it is very well tested.

It may not work the same way for you as it did for me but perhaps it could shrink your tumors or stop the spread of your cancer.
It is known to keep people from dying from cancer.

You have nothing to lose and if you are Stage IV, the doctors should not be withholding a drug that just might save your life.
There are over 3000 articles at pubmed.gov on metformin and cancer.

Just so you know, my metastases were in my liver, spleen, vaginal cuff/outer rectum plus nodules on my outer colon,
kidneys and spleen.  They all vanished without any additional surgery. I had no radiation.

I'd be happy to answer any other question.  You have to target all that is driving your cancer.  If metformin can target two or
three of your mutations, that could be enough for a long life. Remember, it's your life.

Takingcontrol58