Guinea Pig - Metformin Trial

[rhondalea]

I can't put it in my sig yet, because I'm not formally enrolled, but a very kind woman moved heaven and earth to help me fulfill the necessary requirements, so I have an appointment to see the doctor tomorrow. Then on Friday, I have labs and a chest x-ray (and, ha ha, a pregnancy test).

If all continues to go smoothly, I should have a bottle of unmarked pills in hand by the middle of next week.

I almost didn't make it. I wrote to the Canadian doctor who is overseeing the study in April, but then I procrastinated about contacting a local coordinator. I had a couple of reasons for that. The first is that I was waffling about just asking my endo to write me a prescription (no doubt he'd do it), without any worry about ending up in the placebo arm. The second is that I came into a few more factoids about my genetic profile (new studies), and I did some additional reading with respect to supplements I'm already taking, and I got a little scared that maybe metformin is not quite right for me. (Also, even though my A1c is high right now because of anemia and hypothyroidism, I'm actually a natural hypoglycemic. When my whole body went a'wonk before my diagnosis, my endo thought it was possible I had an insulinoma--he knew I had cancer, but he couldn't figure out where it was--so he put me on the Dexcom for a week, and my blood glucose was dropping into the 40s overnight and staying pretty low throughout the day.)

In between, I decided to do something about my genetically-induced brain fog (who knew?), and after a couple of weeks of methylfolate, I woke up yesterday and realized I was being a total wing-ding. Besides which, if I really shouldn't be getting metformin, the powers-that-be (what I call the "universe" and what most of you probably call "G-d" or some facsimilie thereof) will see to it that I end up in the control arm anyway.

So, yesterday, I called the Mount Holly site (because I just don't want to go to Livingston, even if it is fewer miles to drive), and because the one-year anniversary of my formal diagnosis is coming up on May 17 (enrollment must be within one year of diagnosis), we had to move quickly.

Just call me "Speed Racer."

Now I'm sitting here on the porch drinking a cup of tea and hoping the adrenaline will dissipate sooner rather than later, so I figured I'd tell y'all about it.

I'm not convinced my cancer won't return, and I'm not convinced that metformin will make a difference in whether it does return, but I really like the idea of being a small part of something that might make a life-changing difference in another woman's life down the road.

[jml]

I hope you get the metformin. Please keep us posted on how you're tolerating it.
I was put on metformin by an endocrinologist a year after my diagnosis - my NED year - but have been off now for about 2 years. The reason I stopped is 2 years ago when I was trying to get into a TDM1 trial they wouldn't accept me into the trial because it was contraindicated, so since then I've been afraid to start back up just in case I need to search for a trial again in the near future.
I do recall starting up on Metformin can be pretty tough on the GI - lots of diarrhea as your body is trying to adjust - which is a very intimidating and discouraging SE. But once your body adjusts it's fine. I've been thinking about going back on, but I've been wrestling with GI issues lately, so I hope once that settles down I can resume.
Oh, and my date of diagnosis is also May 17.
This year will be 10 years of being Stage IV.

Keep the Faith~

Jml
Dx-5/17/02 - 33 yo; Stage IV - L IDC w/single liver met
1) Herceptin + Navelbine x 8 weeks - No response; progress to innumerable,immeasureable liver mets
2) ISIS 2504 + Herceptin - 6 mos, partial response
3) Taxol + Herceptin x 13 weeks to NED!
NED for 1 year
9/04 - Single liver lesion recurrence
Taxol + Herceptin - on/off to beat back lesion
12/05 - R Hepatectomy; Liver NED until 2009
3/06- Local recurrence - Left breast, IDC & DCIS, but holding treatment while continue to heal from Hepatectomy.
12/06 - L mastectomy + reconstruction through 8/07
10/07 - Recurrence - supraclav nodes
4) Gemzar + Herceptin - on/off controlling nodes thru
9/08 - 7wks Rads to supraclav nodes
10/08 - Acute Renal Failure - nodes in belly stricturing kidneys. placed permanent ureteral stents
Back on Gemzar + Herceptin, but no longer responding.
5) 05/09 - Tykerb + Xeloda - partial response x 5 mos
6) 10/09 - Xeloda + Herceptin - no response, disease progresses
7) 2/10- Ixempra + Herceptin - partial response x 12 wks.
Discovered single brain lesion x 4mm & liver lesions growing while screening for TDM1 + PI3Kinase study.
6/10 - Novalis to treat brain met - SUCCESSFUL!
8) 6/10 - Chemo-embo w/Adriamyacin to de-bulk liver lesion.
9) 8/10 - Screened & Started TDM1 EAP
Immediate response, disease in belly responds dramatically.
2/11- questionable progression of lung nodules
Discontinue TDM1
10) 3/11 - PI3Kinase + Herceptin - intial good response in 1st 6 weeks but LFT's elevated.
11) 7/11-Discontinue PI3Kinase + Herceptin study;
Disease progression - 2 small lesions in colon – docs have never seen this before in BC
11) 8/11 –Start new combo Halaven+Herceptin
10/14/11 -Completed 3 cycles (9 wks)Halaven+Herceptin...
10/18/11 - Scanxiety time -1st scans since starting this regimen
Good interval response, continue on H+H!
10/25/11 – new 2mm questionable spot in brain? Due to Novalis or new disease?
Re-scan in 8 weeks.
1/3/12- Disease progression; 50%increase size & SUV-R lung, middle lobe 6cm lesion.
R supraclav node multiple, miscellaneous nodes in belly. Colon lesions fired up.
12)Herceptin+ metronomic Cytoxan + Methotrexate.
…on a hope & a prayer. Only chemo I haven’t been on is Taxotere.
Hurry up Pertuzumab & TDM1!
Follow Up Brain Scan on 1/18/12…pleasepleaseplease be okay. I can’t take much more.
1/18/2012- 8 new spots in 8 weeks since last Brain MRI
one 2cm spot in brain stem, one 2cm spot in R temporal lobe.
No symptoms, THANK GOD!
1/25/12 – Start WBR x 15 rounds
2/10/12 – Oral Cytoxan WORKING! Melted supraclav node & undetectable by US!
2/14/12 – FINISH 15 rounds WBR;)

[Rich66]

I believe the way Metformin works, it doesn't directly lower blood sugar..it increases insulin sensitivity...which I think means you should be able to take it even if hypoglycemic. Considering it's not very expensive, do you have access to it off label? I bring this up since I found many diabetics and at least one MD thought the branded version was better than generic. Diabetics are able/required to know how well their treatment is working on a daily basis ;)
But I see it's adjuvant, probably a very long range trial.

[rhondalea]

Hi Jessica,

You can be sure I'll be posting myself silly if I start to have SEs. I'm such a whiner. :) I hope your tummy clears up for you soon so you can restart. It really seems to have very high potential for such a simple drug.

Hi Rich,

Well, if I were to bypass the study and go straight to my endo, there would be no problem getting the brand name drug (and indeed, when given the option, I refuse generics, even when it means paying through the nose for the brand). But someone somewhere has to get the placebo, so I'm content to play the odds.

As for the hypoglycemia, I'm glad to hear that. I've got it pretty well under control now, but there was a time when it regularly knocked me for a loop. Eating properly helps a lot. Back when I had no idea what was going on, I self-medicated with Brach's cinnamon candies. They kept me upright, but my brain buzzed like a giant hive the entire time.

The trial is 5 years, according to the informed consent they sent me. I'll be done with tamoxifen before I'm done with this. Sheesh.

[chrisy]

Good for you! And I believe you're right you will "endup" in the right arm for you.

[rhondalea]

I just saw the addendum to your sig, Chris. Woot! I'm thrilled right down to my toes.

[NEDenise]

Hey!
That sounds like a great trial for you! I hope it's everything you are hoping for. In my humble, and only mildly informed opinion...metformin sounds like it has great possibilities for us.

Stock up on immodium...I'll keep my fingers crossed! Whine all you want! You're doing a good thing for the rest of us!

Denise

[rhondalea]

Hey Denise,

No immodium.

I spent most of my day in Mount Holly--going over the documents, giving information, getting information, being examined. And, as I mentioned earlier, tomorrow I have labs and an x-ray.

But no immodium.

I saw your post before I went racing out this morning, so when the diarrhea issue was raised, I asked. They have a protocol for addressing the side effects, but for the proper data gathering, they hope I will endure a certain amount of discomfort in order to see what works and what does not (this is mostly about dose adjustment).

It's okay. I'll live. The rest of this is TMI (you've been warned), but I'll tell you anyway: I have what appears to be some kind of hereditary "slow bowel transit" going on (in addition to the whole hypothyroid thing). This late in the game, I have more control of it than it has of me, but a few months of unplugged pipes would actually be kinda nice. (I'm the only person I know who enjoyed her colonoscopy prep. Well, sort of.)

The good news is that I solemnly promise not to tell you when I'm posting from the bathroom. :)

[NEDenise]

Okay. No "bathroom disclosures"...got it.
And no Immodium...hmmmm
But you can still feel free to whine as much as you need to!
hugs,
Denise

[Rich66]

Do they say how many mg of Metformin used?

[rhondalea]

Well, here's bizarre for ya, Rich. No dose mentioned:

http://clinicaltrials.gov/ct2/show/NCT01101438?term=MA.32&rank=2

...and it's not in the consent document either.

When I go back to pick up my bottle, I will ask what the dose is, and I'll post a follow-up.

Okay, wait, I found it:

http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=102&abstractID=82573

850 mg bid

I'll double check, though, and if the information I'm given is different, I'll let you know.

[rhondalea]

Woot! Woot! Woot! I am officially in the study. I drove to Mount Holly this morning on an empty stomach to have a blood draw. They took enough for a transfusion (well, okay, maybe not, but there sure were a lot of vials). I then received my giant bottle of horse pills, and I immediately popped the first one. Probably not the smartest thing I could've done, but I had a smoothie down in the car, and I was drinking it within five minutes.

Since then, I've had the glassy-eyed headache (classic hypoglycemia symptom for me), mild feeling of threatened nausea (that feeling you get right before you actually start feeling nauseated), a wildly churning stomach after I ate lunch and belly bloat when I woke up from my nap. All that seems promising, except every single symptom can be as easily explained by fasting followed by the two cups of coffee I drank on the ride home. Time will tell, although it's pretty well established that as far as drugs go, I either have nearly no side effects at all or else I have a paradoxical drug reaction. No in-between for me.

It turns out that I was their first enrollee. They do have others in the pipeline, but they're eager to enroll more. If anyone is interested, I'll be happy to give you the name and phone number of the person to talk to (she's a gem) at the Virtua Fox Chase Cancer Program and answer questions about the procedure to get in.

@Rich, the pills are indeed 850 mg (of something), so after the first 28 days, the dose is a total of 1700 mg.