Non-Detectable (0.000%) and potential cure for CML

Ro6ue1 - Fantastic!

I applaud your tenacity and experimentation. I was not familiar with Misoprostol and now I am.

Although what you did is not "statistical" in a clinical trial sense - I have a strong suspicion you are on to something.

I wonder - given that your doctor helped you on this - if you and he would write a paper for publication so that the greater community can try this approach even in the absence of a formal clinical trial. Clinical trials are expensive. There would be no value to a pharmaceutical company in conducting one. But patients and their doctors might be able to amass data leading to anecdotal success.

I am already PCRU (for over two years) - when I try TFR - if it fails, I will resume my drug, but this time adding misoprostol to the program. Could work!

Bravo on your effort!

Thanks Scuba and good luck on TFR!  I will ask my doctor about the documenting it, he seems pretty conservative (except for the prescription), won't let me stop or lower my dosage so will likely go back to my expert that I started with at some point who was on board with either of those.  I'm not sure if he would be interested in writing one but can at least ask.  I once told one of my oncologists that there may be a link between high triglycerides and CML.  Before I was diagnosed, for two years my triglycerides had been rising, after diagnosis and lower CML numbers, they returned to normal.  He was not interested in writing about it though, might ask some other experts.  

Hi Sarah, just read your post, great news on your reduction and so fast!  With so many combinations of things you were trying, who knows which worked, maybe all three did.  I will look into the fish oil and Sodium Selenite too.  So happy to know I'm not the only one that has tried this, I'm guessing that quite a few have globally after the research was released.  I'm also happy that the researchers are not angry, I was not sure if they would be since we are kind of piggybacking on their research and they are not benefiting (financially) from it.  I'm sure Big Pharma won't be pleased if this does get out and it does in fact work.  Until we get more data (two sets so far look great!) then we won't know for certain. 

Did you have any adverse affects from taking the Misoprostol?  What was your dose and how many times per day?

I hesitate to give out my doctors name without his permission, I was actually concerned about even asking him for the prescription, wasn't sure if I might get him into some trouble or not but he did not seem too concerned.  Interestingly, Misoprostol is also sold at pet stores for dogs (still need the prescription) but that may be another route (black market, dark net, being the other). 

I'll write to the researchers also and let them know my results.  So glad that they are not angry!  

Here is my dose chart: 

2/25/19   8 grams EPA only Fish Oil per day plus 2 Tbs Sodium Selenite, divided into two dosages per day. I continued this through 3/10/19. (Edit: I took 2 Tbs Sodium Selenite twice per day, 4 in total). 

3/11/19   800 mcg Misoprostol (divided into four dosages throughout the day). Then increased Misoprostol as follows: 

3/12/19 1200

3/13/19 1400

3/14/19 1800

3/15/19 2000 daily through 3/17/19. This was intense dose so I dropped back to: 

3/18/19 1600 daily, and continued this dose through 3/25/19. Then stopped Misoprostol and went back to: 

3/26/19 The above Fish Oil and Selenium every day through to 4/10/19 when my PCR test was done 

4/10/19 PCR .0532

I have to work full time to keep my health insurance so I divided Misoprostol up throughout the day. I still had diarrhea but I luckily made it to the bathroom!  LOL.  I had nausea the first time I upped my dose to the 2000 level but I plowed through and didnt have it again. 

Howard Xue said he thought it was the combination. Prabhu asked what form of Sodium Selenite I was taking. Penn State is studying the Selenium now, after their latest research. 

Hi Kirk, 

Yes this is fascinating!! I can share my two cents and look forward to what ro6ue1 will add. 

Per the murine models Misoprostol works with or without TKI, and in fact superior to TKI alone, but best results were the two together. 

Misoprostol is ProstaglandinE1 (PGE1) derived from EPA Fish Oil. PGE1 is endogenously manufactured in healthy bone marrow, but that process is hampered in patients with CML. There are pathways they are still detailing to nail down precisely what goes wrong. In the meantime when they injected CML mice directly with PGE1, the leukemia stem cells were killed, (bypassing the need for their bone marrow to make PGE1).

PROBLEM is, Misoprostol’s “injectable” analogue “Alprostadil” (aka Caverject) should NOT be injected in human males who have leukemia!!!!  This is because men with leukemia are prone to priapism (prolonged, painful, irreducible erection) while Alprostadil is used to treat erectile dysfuction by injection (directly it into the penis shaft for a two hour erection). So accordingly the Alprostadil insert advises against use if you have leukemia. (They are assuming injection into the penis, however). This gets complicated to unpack. :/ 

Misoprostol, on the other hand, causes abortion in pregnant females and is used to initiate labor in a full term pregnancy if labor is stalling. So women should take care with Misoprostol, never use if pregnant, could become pregnant or breastfeeding. 

You can see why Human trials could be complicated to get through the FDA approval process. (Not to mention the obvious major profit loss factor).

BUT WAIT, Misoprostol is taken safely by both men and women by mouth to treat stomach ulcers!  It’s taken all the time!  It coats the stomach, providing a lining in between stomach contents and stomach acid. So (as you mentioned) I take Misoprostol at least 2 hours before or after Dasatinib since Dasatinib works best in stomach acid. 

The thing I want to do differently though is take the full dose all at once instead of smaller portions through the day. The mice were dosed once per day, full dose. Here is a quote in the patent, on dosage (FYI):

”In the experiments described herein, the amount of .DELTA..sup.12-PGJ.sub.3 used to eradicate LSCs was calculated to be 0.6 micrograms/day/gram mouse for 7 days. Generally, the dose is in mg/Kg subject/day=ug/g subject/day. In a typical embodiment, a dose in the range of about 0.025 to about 0.05 mg/Kg/day is administered. Such a dose is typically administered once a day for a few weeks.”

(You can find conversion tables online if you want to work out the mouse:human ratio using these variables).

BUT REMEMBER, this (above quote) dosage is for injection. So I just took the usual maximum dose for a human female pursuing abortion (1600 mcg) and I increased that to what I could manage during a work day by dividing it into small doses. But I think it needs a major impact all at once every 24 hours over many days. I seem to recall in one experiment mice were injected for 18 days.

That all being said, it was later discovered (Penn State) that Sodium Selenite restores the endogenous production of PGE1 inside the bone marrow by “jump starting” the tumor suppressors back into normal functioning. If that works you of course do not need to ingest the PGE1 because your body produces it again, on its own. 

I will try and post a study on the Sodium Selenite here. Oh but before I forget, (you will see in the study) NSAIDS interfere with the Selenium. So I only take CBD oil or Curcumin for pain and inflammation. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102641/

I notice this article is from 2014.  What have they been doing about this since, research-wise?

Hi Kat73,

You can find info on latest research at Penn State web site. I wrote to Dr Prabhu who told me (in February) they are in the process of revising their application to FDA for clinical trials on Selenium. I am not going to hold my breath on that. The Fish Oil (Misoprostol) has been know since 2011. Someone brought it up on this forum in 2012. If you search “Prabhu” on this very site you will find the historic thread with Prabhu’s email address which is how I first contacted him. His research with Fish Oil led him to the selenium. I assume the human trials are stalled because the powers that be do not want a cure found. Think of the profit loss!!!  Pessimistic, I know... But maybe that’s just me. 

Important to note: The fish oil used was EPA-only Omega 3. At high dosages take care to ensure it is not tainted with mercury.

You might be right!!  👍🏻

Oh, this (on Brazil nuts) is a really good find! Thanks for sharing!!  In fact after I ordered my sodium selenite (while waiting delivery), I went to my local food coop and got Brazil nuts!  So who knows, maybe that works just as well. 

The reason I went with Sodium Selenite ultimately was the reference made in one of their papers. I found the quote here for you: 

“Interestingly, treatment of these splenocytes containing LSCs with various forms of organoselenium compounds, such as MSA, Se-Met, and p-XSC, showed differences in the ability of these selenocompounds to target LSCs (Fig. 2B). Although not as effective as inorganic selenite, MSA was relatively more effective than Se-Met and p-XSC to cause apoptosis of LSCs. Taken together, these findings demonstrate that the ability of selenium to target LSCs for apoptosis is dependent on the form and dose of selenium.”

I don’t know which form of Selenium is in the Brazil nut. Sodium Selenite was the inorganic type they used here and is allegedly more bio-available. I’ll try to attach a link to the paper.  Look at Figure 2 (B) comparing Sodium Selenite performance to the other types. Also there are photos comparing spleen sizes with and without the selenite. Figure 4(F) compares performance of Prostaglandin (top bar) to various Selenite dosages and also with or without different NSAIDS (which inhibit). Figure 4(G) shows impact on Blast Crisis. 

Either way it looks like selenium is a good idea, just seems the selenite is superior. 

http://cancerres.aacrjournals.org/content/74/14/3890.full-text.pdf

Scuba,

I hear ya, and yet mice were well good enough for testing the TKIs and we embrace the result. So maybe less a roll of the dice on this one (?). 

Anyway, the research on selenium (and fish oil and Misoprostol) predates 2014 by decades and continues today at robust levels. That (one) paper I linked happens to offer the most detailed info comparing “types if selenium” (your question) which is why I linked it (and impressive spleen photos) but is not by far the last. Don’t forget, also, dosage of selenium is key for CML. Problem is, any (and every) potential cure poses immediate intolerable threat of profit loss in the *hundreds of billions per year* and the FDA (approving agency for all human studies) is in the right pockets to prevent such travesty. 

As far as “adequate selenium” goes, that seems to tip the scales on kick-starting  pioglitazone (Metformin) which mysteriously sometimes cures and sometimes doesn’t. That’s another whole area; If you are interested in those papers, I can provide links. But this whole pursuit is exhausting to undertake given the mountain of skepticism that wins out in the end. 😞 (sigh!). 

Which is why it’s so exhilarating to find kindred spirts on this path. And for that reason, I’m grateful just to be permitted to share. Thank you.

How did you decide what dose of misoprostol to take?  Did it have any correlation to the dosage given during the murine model experiments?  

For myself, I decided to try the standard dose at first, just all at once instead of spreading it out throughout the day.  In some of the research papers I read on the combination, they were giving it to mice at the same time as the Imatinib.  I went to the higher dose later on since it was a known safe dose for pregnant women (looking to abort).  

I'm wondering about the timing of the doses also.  

I thought about the timing also, thinking that my stomach wouldn't have the acid to digest the Imatinib; never had an issue.  If you can I recommend taking the Misoprostol one hour after taking your TKI, that way your stomach has had time to digest it and the one hour difference shouldn't make any difference in how effective the combination is.  
 

Does the misoprostol require a TKI to do its work against CML stem cells or is it a totally separate pharmacodynamic process?  

This one I'm not sure of, maybe?  I wouldn't recommend only taking the Misoprostol since it may only affect the stem cells and not their progeny and the best test results were when used in combination.  

Hello Scuba,

Did you take any multivitamins during the treatment of Misoprostol and the TKI ?

I am currently on Bosulif 300mg daily.  I was also taking multivitamin (twice/day) to help with QT/electrolites problems that maybe caused by Bosulif.

I started the Misoprostol 4 days ago (200 mcg x 4x/day) but I was afraid to continue the multivitamin, as I don't want anything to interact with Misoprostol. But it has been 4 days since I resumed on the Bosulif and I am starting to feel again the flapping in my chest. I am wondering if you used any multivitamins or supplements during your treatment?

Also, since you have reach ND, what do you do next ? Do you keep taking the Misoprostol ?

Thank you,

Did you take any multivitamins while on Misoprostol ?

At what point did you increased the dosage from 800mcg to 1600mcg daily ?

Thank you

Ok. I just got my August 13 PCR result: .0083

June 14 was .0134

I was on 20mg Sprycel and for 14 consecutive days between these tests I took 1600 mg Misoprostol all in one dose at 6:30am. I took my 20 mg Sprycel at 8pm every night.  

It’s another huge drop. Almost Undetectable now. The lab test is only sensitized to .0069

Yay!!  

ro6ue1,

I am also beginning to flirt with taking flight into this without a TKI to see what happens. 

I just analyzed all my notes. It’s been for me an average of a 1-log reduction per month on Sprycel progressing with dose reduction.  Here is my outline: 

Started 32% PCR

Month #1  100 mg  (Then a 6 week break);

Month #2    80 mg  (Then a 4 week break);

Month #3    50 mg x 2 weeks then split to 25.

Month #4    20 mg

Ending PCR is .0083 achieved between Jan and mid- August 2019. 

Has anyone ever had a 1-log average reduction per month on any TKI alone?  That is my question now. 

I have had the general experience of achieving a better PCR on a reduced dose of Sprycel after breaks for pleural effusions.  I have always chalked it up to a phenomenon, but I can see that research is beginning to get around to looking at this.  I'm at MR4+ on 20 mg and am so tempted to "test" the "theory" by stopping and restarting or taking one every other day, just to see if I could nudge things into undetected.  Unsupportive oncologist, however!  My personal experience has been that the CML comes back really fast during a break.  Sarah, did that happen to you?

Wow that is a huge reduction all at once.  Do you mind sharing some about your history since then?  

So, let's serve up the pasta tossed with fish oil and topped with mucho white dairy, ground Brazil nuts and flavored heavily with turmeric - party time!!  I'll eat it every day if it works.  Die, you stem cells.  Come on, University of Pennsylvania!

(Lest anyone misconstrue, I'm being lighthearted here.  And serious! )

Hi ro6ue1,

Where you taking both the Tasigna and Misoprostol 2 to 3 times/week ? What dosage were you doing on Misoprostol? What dosage will you be doing now?

I will have my PCR test in 2 weeks.

Thank you,

Resurrecting this post for new members.  

I have been NDR for two consecutive tests, next test is in November.  

I am still taking Misoprostol, not as frequent as before but just to get me back to NDR.  Currently I am taking it a few times a month.  

Also worth mentioning is I have kept NDR while skipping doses occasionally and reducing dosage (200 mg).  I have changed doctors back to my original doctor who I began my CML journey with and he is accepting of both dosage reduction and stopping medication (after two years of NDR) so keeping my fingers crossed on staying NDR.  

If anyone else has been taking Misoprostol, would love to hear your results!

Are you still taking misoprostol at the same time with Imatinib or after some gap of few hours .I'm very intrested in your experiment & you got very good doctor .so plz keep updating frequently as possible. Looking forward for your reply.
Wish you all the best.

I take it at the same time now, haven't had any issues. 

Next blood test is next Monday, will find out the results (if not delayed due to Covid like last time) in two weeks.

Fully off my TKI since February and feeling a lot better being off of it, still Non-Detectable with monthly testing. Next test is July, and if that one is also ND, then I go to two month testing.

July test still ND.

Not detected for October, doing 3 month tests right now. For the first six months after stopping medication was doing monthly testing, changed to 3 month in July.

Any updates to your story? I am curious as to the outcome