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Has anybody been able to reduce their dosage of Sprycel?

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http://www.cancernetwork.com/chronic-myeloid-leukemia/destiny-cml-patients-stable-molecular-responses-safely-halved-tki-dose

With the promising studies showing patients remaining undetectable after stopping treatment of TKIs, I wanted to find out about lowering my dosage since I've been undetectable for 3 years now.  I spoke to my doctor today about these studies, but he said that he isn't willing to try anything other than the standard of care. (I've only seen this dr. twice due to my insurance changing and no longer being able to see my original doctor). While I can understand his reluctance, I am disappointed. While I am thankful for TKIs and the significance of  being able to treat CML with a pill a day, I wish I didn't have to deal with the side effects, even though mine are not as bad as some people experience. (I miss having energy and more hair and could do with a lot less diarrhea).

The article linked above is the article I am referring to about reducing dosage. (I am having trouble formatting in this forum and am unable to cut and paste to move the link into the proper position).

Yes, I dropped from 100mg to 70mg six months ago. Results are holding, so after a good discussion with my doctor last week, if nothing changes in the next while we'll drop again to 50mg. Who knows after that? 

David 

Your doctor is misinformed and not up to date.

Standard of care for patients who have been "undetected" for two years can stop taking  their medication completely and test remission or reduce dose.

There are on-going cessation trials and results are in. Those who stop  close to 50% will not relapse. Of those who relapse ALL regain response after resuming therapy.

In your case, you should consider at a minimum reducing your dose - especially Sprycel (avoid potential long term side effects such as pleural effusion)..

I was started on 70 mg sprycel and reduced (by my doctor) to 20 mg Sprycel where I remain today. I am also PCRU.(for last 9 months).

My husband’s doctor was very negative when we first discussed reducing his dosage. He said that he would be on 100 mg for the rest of his life , or as long as he could tolerate the dosage, which was v disheartening given all the side effects that may develop, esp after a couple of years. 

At our our most recent appointment he could tell I had really done my homework and he was happy to accept the research papers I brought along. He emailed after to say we can discuss dosage reduction at the next appointment which will be 7 months after diagnosis if test results are good. I think what made the difference was taking along peer research. 

I hope this links to the paper that I got from Kirk that specifically talks about reducing dosage to 50 mg in newly diagnosed patients. 

http://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.e18551#affiliat...

 

best louise 

 

Louise,

Lower dosages are of course something many of us strive for. But only 7 months after diagnosis is pretty quick to look for one. You're certainly into territory where there is not much research by reducing that soon.

Others will know better than I do about results from the DESTINY trial here in the UK and other similar global ones, but as I understand it time on therapy (presumably full-dose) is a factor into how successful subsequent stopping (and reduction) seems to be.

David.

I’ve read studies that lower doses of Dasitinib have equal
efficacy as the standard dose on >60 year old patients.
Younger patients have not been studied. Or at least to my
knowledge. It seems that CML at a younger age is more robust
or medicine is more strong depending on the age of the person
Mutations notwithstanding.

This is not a hard and fast rule. It’s Statistical data.
I lowered my dose from 100 to 50, and it’s A-OK.
But then I’m older and don’t got much to loose.
“CML is the most exciting thing to happening to me
since I lost my virginity. And I’m an agnostic.”

(It’s O.K. to have some fun...)

Romo

Thanks for the input David. We have been very much influenced to push for a dosage reduction because of all the reading I have done about the long term side effects of being on 100mg Spycel, including PEs. Even at 5 months in I have already noticed that every month on Sprycel I am seeing a slow build up of side effects in my husband, particularly on the inflammation side. He has responded extremely well to Sprycel -ABR  89% To 0.7 % at  3 months ( he was at 200k WBC, with an extended spleen when diagnosed). So we would like him to be able to continue on this TKI and not have to come off at some point because of side effects. 

There is a very promising study out of Texas showing very good results starting newly diagnosed patients on CML at 50 mg. I think it’s worth it for us to try a reduction if it’s closely monitored. Having no family here, health insurance tied to being able to do a very demanding job, all factor in as well. 

Romo I hadn’t read about the difference reactions over aged  60 compared to under .I would be interested to learn more.  My husband just turned 50 last year ( CML was pretty much his birthday present). He was blaming all the CML symptoms he was experiencing prediagnosis etc on getting older.

An 89% to 0.7% drop in three months is an outstanding result. Your husband can certainly reduce his dose by half and his PCR will continue downward.

http://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.e18551

Dr. Cortes is my doctor (co-author of paper linked above), he never started me at 100 mg. I was started at 70 mg and then for only a week. My dose was dropped to 20 mg. My PCR continued to fall and leveled off at < 0.01% for a couple of years and now it has fallen to "undetectable". I continue on 20 mg.

Sprycel is a "threshold" drug. It is not as dose dependent as other TKI's (notably Gleevec). Threshold means that a minimum amount of drug is necessary for response to occur. Once response occurs, more drug is not better (or cause faster response). The key is finding what that threshold level is for each patient. Clinical trials by their nature are averages tied mostly to safety first and efficacy second. 100 mg is what came out of the statistics. What they are finding now (with many more data points - which is us!), is that 100mg is not necessary and potentially much more toxic. 50 mg is likely a better starting point (see paper). There will always be patients who need more drug to get a response (some as high as 140mg), but many don't even need 50 mg (I am one of them). Part of the reason for Sprcyel's threshold response is its very quick half life (5 hours). The drug is quckly absorbed, does its job and is then metabolized quickly. It is a very potent drug. 100 mg is simply not necessary for many patients.

Given your husbands outstanding results, he can certainly consider cutting dose - maintain his response trend and likely avoid side effects he can feel.

I have no side effects that I can feel. I look forward to when I stop taking Sprycel altogether.

(full disclosure: I am not a doctor. Comments made by me are my opinion based on much reading and study. I am a scientist)

Thanks for the info. Yes, I do believe my dr. is misinformed and not up-to-date, too. I think he deals more with general oncology and less with hematology. At my first appt. with him 3 months ago the only records he had from my previous doctor (who I had since diagnosis 5 years ago - dx at 44 years of age) was my last blood test result. He didn't even do more blood tests at my last appt. That was the first time that has happened to me in the 5 years since diagnosis. But I was so disappointed and deflated at the appointment, I didn't even think to ask. He just said come back in 5 months. So yeah, I do believe I need to find a new doctor.

I was not aware Sprycel was a "threshold" drug. I will be talking to my next doctor about a dosage reduction.  Thanks.

I started on 100mg/day on February 2.  I was feeling pretty crappy by the 13th so I started cutting them in half.  I think I'm feeling better now. smiley  Oh, and it's a good thing I've been cutting them because UPS lost my Sprycel and I'm running low. frown

So given that Sprycel is a 'threshold' drug, in the case of someone like me, who has plateaued on 50mg Sprycel for one year since dropping from 75mg to 50mg (see below) does that mean I need a higher dose to reach the 'threshold'?

CML diagnosed April 2016
Initial WBC 90 000 Blasts 2%

Type One Diabetes diagnosed April 1980 (age 12)

BCR-ABL (IS)
46.77  April 2016
3.568  July 2016 
0.076  Oct 2016
0.016  Feb 2017
0.0079  April 2017
0.014  July 2017
0.019  Sept 2017
0.011  Nov 2017
0.019  Jan 2018

Sprycel
100mg April 29 - September 22
75mg  September 23 - October 28
50mg October 29 2016 to present

It could very well be that you need a higher dose, but given your current  PCR level,  you are doing very well on 50 mg.

Any PCR < 0.1% is very good and has excellent long term prognosis. You could stay the course and over time your PCR could resume dropping. Plateau's can last years.

Likewise - increasing your dose is not likely to change your plateau hence the 'threshold' already being  passed.

https://www.ncbi.nlm.nih.gov/pubmed/28396095

 

Romo

I only take 20 mg Sprycel and I am currently PCRU ("undetected").

Patients should find the lowest possible dose that works. More is not better. More is more toxic.

Thank you for posting that article Romo: Elderly Patients With Chronic Myeloid Leukemia Benefit From a Dasatinib Dose as Low as 20 mg.

For anyone who missed the conclusion of this study of 21 elderly patients on 50mg and 20mg per day Sprycel here it is:

CONCLUSION:

Low-dose (eg, ≤ 20 mg) dasatinib therapy generates an adequate molecular response in most elderly patients with chronic phase CML without causing severe AEs.

This explains why Dr Shah starts his patients aged over 60 on 50mg/day Sprycel

Romo, thank you also for coining the phrase 'descending plateau' ... this gives me a real tickle ... Ha! Descending plateau. I love it!

Thanks scuba

I always appreciate your input, advice and inspiration.

I do know that Hannibellemo from the old US site was at around BCR ABL 0.02 IS for a year and a half and then dropped down to PCRU. I think she, and a couple of others including Marnie, got sick of pleural effusions and did not want to increase their doses from 50mg (Marnie may have been as low as 25mg). 

Then there are others like CallMeLucky from the old site who reduced down from  100mg Sprycel per day but found their BCR ABL levels crept up so increased back to 100mg and have now been PCRU for some time.

I guess there are all sorts of reasons people respond differently and also some of us have other health issues to contend with, meaning we can't always take 'full dose'. I'm just hoping that one day I can take less Sprycel so I can get back onto the strength of enalapril I need to protect my kidneys. In the meantime, I'm taking Curcumin :)

 

RC Kirk, Did you have any bad side effects from breaking them 1/2?  My doc won't let me since there are warnings all over the bottle and it is prohibited by the FDA.  I have thought too, about just breaking them but was worried about how the pill was formulated that it would ruin my stomach or wouldn't be effective.  Did your doc OK that since I am sure insurance wouldn't pay for another Rx or were you tired of the high dose and wanted to experiment?

Scuba, Thank you for this information! My doc dropped me from 100 to 70 after 3 months of treacherous side effects but only after I had a mini breakdown in his office. He said he would only drop me to 50 if forced to by a PE.  I was 89% at diagnosis and went into MMR at 3 months and 6 months it is still completely undetectable.  This 70 mg is crushing me with side effects.  May I ask who your Dr. is?  I may travel to him for treatment.  I am searching for another doc in my area but all roads keep leading back to my current group.  I am very frustrated at the current moment because I have had 2 hospital ER visits where I had phantom chest pain going to my shoulder and am now the ower of 2 heart murmurs.  I also deal with inflammation and exhaustion every day. I think it's time to switch docs!

Mamjo .... After only six months of Sprycel, you are 'undetectable'.

YOU absolutely do not need 70 mg sprycel.

Consider reducing your dose to 20 mg and test again in 3 months. I suspect your PCR will remain "undetectable".

In fact, after a couple of years on 20 mg and remaining undetectable, you could stop taking Sprcyel completely and test for treatment free remission (TFR). I envy you. You lucky dog.

(My doctor is Jorge Cortes at M.D. Anderson Cancer Center. We communicate by email now - I haven't seen him in years. Every six months I get a blood draw. Next year, I will try stopping my 20 mg Sprycel and test for TFR. I believe I will succeed given my fasting program).

 

 

Mamjo

i am so sorry to hear about your doctor. We are in Northern California. My husband’s oncologist agreed to reduce his dose to 50 mg at 6 months. His PCR at that time was 0.15. 

have you shown your doctor any research papers showing lower dosages can work? This is what persuaded my husband’s doctor. 

Dont give up trying to get a dosage reduction. It may be worth trying to see a CML specialist if your oncologist won’t budge.

 

louise 

Mamjo,  I don't think I have had any bad side effects from splitting the tablets.  Others have done it before and they're still around, so I figured it probably wouldn't kill me.  My doctor has no curiosity (or maybe he's just looking out for his malpractice insurance provider).  I've been experimenting with alternating dasatinib and imatinib and it seems to be giving me a good result so far.

As I understand, you just have to be careful with any dust created when splitting the tablets.  You don't want to inhale it or get any in your eyes.

I started splitting mine with a pill splitter a few months ago and haven't noticed anything different from handling/splitting them. I know it says on the bottle not to - but I'm thinking that may be a generic warning about chemotherapy drugs.

So just an update - 3 months ago I started cutting my 100mg dose in half by splitting the pills. Immediately had no more diarrhea - which was great. Had more energy (could have been because I started iron therapy for my anemia though). Just got my latest test results back and am still undetectable. Yay!

Of course my doctor doesn't agree with me lowering my dosage, but not much he can do about it. I am going to continue with the 50 mg for another 3 months and see how my blood tests come back then. If I'm still undetectable I'm going to reduce my dosage again to 20mg. I'm cautiously optimistic.

Does your doctor know of your results while on 50 mg?

 

I was diagnosed June 2014. Was MMR three months after diagnosis and PCR kept getting lower over time. Doctor reduced me from Sprycel 100 mgm to 70, because I was PCRU. I remained PCRU and was reduced to 50 mgm. 

I continue to remain PCRU and want to drop to 25 mgm, but he won’t. He says if we go too low, I could develop resistance just like we do with antibiotics.

He said he would rather I stop entirely rather than reduce further. I want to reduce first.

In summary, there are some docs who just don’t feel comfortable with too much reduction. I am thinking about going to Cortes to get a second opinion too.

Can you provide links for these trials.  I have had CML since 2005, started on Gleevec 600 mg, went into remission then it stopped working.  In 2007 I was switched to 50mg Sprycel and have been in remission since 2008 (10 years).  During that time frame I have seen 3 different drs and all have told me I cannot stop taking it as trials have shown that no matter how long you are off it the CML eventually comes back.  If there are trials out there now showing that you can come off it and be "cured" so to speak, I would love to know and shop this to my doctors as both the Gleevec and the Sprycel have caused me severe bone pain which, due to the amount of pain meds I am on required me to go on to disability.  Believe me I would love to have no more pain.  Thank you, Wendy

I have been on Sprycel 50mg for 11 years (was diagnosed in July 2005 and Gleevec was first med I was on, it stopped working).  I have been in undetectable for 10 years so there should be no reason you cannot reduce your dose.  Your doctor may just be overly cautious or is not keeping up to date on new reports and trials.  Best wishes to you, Wendy.

Yes, I have been able to reduce the dosage of Sprycel.

Diagnosed with CML Feb 2018.

I started out with 100MG daily- ( March 2018)  and it was miserable regarding side-effects

I had had enough after  3 weeks!

No appetite, fluid in lungs, no energy what so ever. I could not even lean over to put on a pair of socks with-out having to catch my breath or walk maybe 10 feet  and felt like I just ran a marathon!

Dosage was dropped to 80 MG and after 5/6 weeks- again bad side effects- loss of appetite, fluid in right lung.

Dosage was dropped to 50MG about 1 and 1/2 months ago and the difference is amazing.

Appetite is back, have much more energy, very little fluid detected in right lung, no loss of breath etc and the WBC, BCR/ABL etc numbers so far are real good from July.

I have new blood work scheduled for the end of Aug.

All the best,

Chuck

 

 

What do you guys think of dosage reduction with history of BCR-ABL mutation ?

I’m in MMR 4.5 with 100 mg of Sprycel since 1 year 

my Haematologist says it’s not safe

Cheers 

Mike

"He says if we go too low, I could develop resistance just like we do with antibiotics."

Your doctor is mis-informed. There is no such thing as "resistance like antibiotic resistance" in cancer.  Cancer is the result of a genetic mutation. Targeted specific drugs work on that mutation. It is a chemical pairing/reaction. In the case of Sprycel, taking a lower dose might actually be MORE effective since Sprycel also suppresses the natural immune system needed to fight CML in the first place.

I do agree with your doctor on one idea - stopping Sprycel altogether to test 'treatment free remission' (TFR). Given your PCRU status and quick response - you are an excellent candidate for trying this and having success. There is no risk to trying as you can simply resume Sprycel if you lose PCRU. You will quickly regain PCRU if you have to resume. On the other hand, you might find that you remain in remission without taking a toxic side effect induing drug month after month after year after year. How nice that would be.

(note: I did try cessation myself and I was only MMR at the time - PCR < 0.01%) and went nine months without taking my 20  mg Sprycel. Although I never lost MMR, my PCR did rise from a barely detectable level to around 0.08%). It went up and down during this time. I decided to resume Sprycel to test that it would drop me back and it did - within a month. I will try cessation again once I hit the two year mark of PCRU. And I will test cessation again and again until it works!).

 

Not sure if you are still cutting your doses in half but any doctor I have spoken with and the pill bottles state to not take broken pills or break them.

I was left with a bottle of 100 mg Sprycel when my dose was lowered to 80. Hoping to eventually drop to 50. I phoned the pharmacist at the special pharmacy for CVS (USA) and asked about problems that might occur with cutting Sprycel.  It is not extended release so that is OK.  The other question is that it might degrade or be dangerous to take in cut form. She did not think so,

i would advise anyone thinking of splitting these $$$ pills to check with pharmacists.    Gitel

No I'm not quartering my 100 mg Sprycel tablets any longer.  I told my doc what I was doing and seeing the excellent PCR response I've had so far, he gave me a prescription for two 20mg tablets per day.  I've only been taking one tablet per day, and you know, it is much easier to split the dose when it comes in two tablets. wink

They tried to talk me out of cutting the tablets by telling me the tablets had an enteric coating.  I think they gave me incorrect information. The information I found about the coating is that it's designed to keep medical personnel from accidentally getting any drug on their hands if they handle the tablets.

If you do cut the tablets, be very careful with the dust that's created.  Probably the best way to deal with it is use a damp paper towel to wipe away the dust and then put the paper towel in a plastic bag before putting it in the trash bin.

I agree with Kirk.

Sprycel is film coated with I presume a digestible wax.
Formulated to degrade in hydrochloric acid. The Stomach.
When I took my 100mg tabulates I could feel it break up
in my stomach within a few minutes. I took it in the AM before food.
I heard it described as like a bullet to the gut. Perhaps that’s a little
exaggerating but I could feel it unmistakably breaking up and a body flush followed.

The coating is to keep the pill intact in humid environments.
And so it won’t transfer to the skin if the hands are wet.
It has nothing to do with a time release feature.
The medical community will not recommend breaking pills
because it’s like allowing the patients to assign their own dose.
I respect their position on this. They are wonderful dedicated people.

 


Romo

I agree with Romo who agrees with Kirk - so that means I agree with Kirk. But I wonder if Kirk agrees with Romo who also agrees with Kirk.

Yes, I agree with Romo! And, I concur with Scuba!

Sometimes my onc finds me disagreeable, but we're working it out. wink

I dare say,  If there is not a disagreeable bone in my body at this moment!
On-ward to other challenges!


Romo

8 years ago diagnosed w/ cml, prescribed 100 mg's, got every side effect the med has to offer, but my cml is barely detectable, after being on for 4 plus years I got the dreaded pleural effusion, doc lowered dose to 50mg's, I had a surplus of the 100 mg (off of sprycel for 4 months until pleural effusion left) so I cut in 1/2, cml still barely detectable. 

Is it better to take the whole pill every other day or to cut in 1/2 and take everyday! 

I'm also thinking of cutting my new script of 50 mg's in 1/2 because my copayment, starting in 2020, will be $600 dollars.

I appreciate anyone's help and guidance, thank you in advance. 

 

8 years ago diagnosed w/ cml, prescribed 100 mg's, got every side effect the med has to offer, but my cml is barely detectable, after being on for 4 plus years I got the dreaded pleural effusion, doc lowered dose to 50mg's, I had a surplus of the 100 mg (off of sprycel for 4 months until pleural effusion left) so I cut in 1/2, cml still barely detectable. 

Is it better to take the whole pill every other day or to cut in 1/2 and take everyday! 

I'm also thinking of cutting my new script of 50 mg's in 1/2 because my copayment, starting in 2020, will be $600 dollars.

I appreciate anyone's help and guidance, thank you in advance. 

 

8 years ago diagnosed w/ cml, prescribed 100 mg's, got every side effect the med has to offer, but my cml is barely detectable, after being on for 4 plus years I got the dreaded pleural effusion, doc lowered dose to 50mg's, I had a surplus of the 100 mg (off of sprycel for 4 months until pleural effusion left) so I cut in 1/2, cml still barely detectable. 

Is it better to take the whole pill every other day or to cut in 1/2 and take everyday! 

I'm also thinking of cutting my new script of 50 mg's in 1/2 because my copayment, starting in 2020, will be $600 dollars.

I appreciate anyone's help and guidance, thank you in advance. 

 

It's been nearly a year since I originally posted and also, stopped taking Sprycel (after a tapering off period of months) after this post at the end of December 2018.  I am happy to say that I am still undetectable!  It has been such a relief to stop taking the drug and not deal with the side effects and the expense.  And I am feeling incredibly grateful and fortunate.  Had I listened to my doctor I'd still be on Sprycel unnecessarily.  To sum it up, do your research and challenge your doctor if they are not up to date with the current information.  This is your health and you need to take charge of it and keep up with it.  Thank you Scuba, for your help and information and support to all those on this forum.  

It's been nearly a year since I originally posted and also, stopped taking Sprycel (after a tapering off period of months) after this post at the end of December 2018.  I am happy to say that I am still undetectable!  It has been such a relief to stop taking the drug and not deal with the side effects and the expense.  And I am feeling incredibly grateful and fortunate.  Had I listened to my doctor I'd still be on Sprycel unnecessarily.  To sum it up, do your research and challenge your doctor if they are not up to date with the current information.  This is your health and you need to take charge of it and keep up with it.  Thank you Scuba, for your help and information and support to all those on this forum.  

Thank you Scuba. You are very knowledgeable, and your responses are always illuminating and very informative.

Especially where I am concerned as I am on Dasatinib myself.

Too bad I can't follow the threads all the time as even though I subscribe to notification of updates I get none.

Take care.

pigeon

Hello to all,

in response to this thread, I have been on 20 mgm of Sprycel as well for several months and still undetectable!! No side effects and all blood work is normal. 

My onc says I am doing well for now. Not sure what he means by that, but possibly wondering if I will develop resistance at such a low dose. That was an initial concern he had. I have learned On this site,  the body doesn’t develop reactance to this drug just because of being on a low dose.

i am happy with the decision to lower the dose since I was undetectable for two years already.

Haven’t posted for a long time, because my job is incredibly busy!!