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Looking for resources to aid discussion about lowering dose of sprycel

I was diagnosed 1 year ago with chronic phase cml and I recently reached MMR with a bcr-abl of 0.054. I would like to have a discussion with my doctor about lower my dose of sprycel. She does not seem to want to do this and has stated that the standard of treatment is 100mg per day and that the dose is never lowered as long as it continues to work and I don’t experience any side effects. I am only 31 and i have concerns- I don’t want to develop a heart condition and I also have serious concerns about the medication impacting my fertility. Any suggestions for bringing up the subject with my doctor again? I would like to be more confident the next time - perhaps this will prompt her to take me more seriously.

Any suggestions are greatly appreciated!

"Early results of lower dose dasatinib (50 mg daily) as frontline therapy for newly diagnosed chronic-phase chronic myeloid leukemia."

Dr. Cortes, co-author of the above paper, is an expert in CML. He writes the guidelines and is now suggesting 100 mg is too  much to start.

I was never started at 100 mg and I was borderline accelerated phase. Now, I only take 20 mg daily and I am "undetected".

Given your excellent response, you should suggest a 50 mg dose. You can always go back up. If your doctor claims CML will become resistant, get a new doctor.

Thank you so much! I’m in the US and I actually have 2 doctors - my main oncologist and a second opinion. I just don’t understand why neither of them are willing to discuss this with me. Both are acting like dose reduction is some big unknown and both have made mention that it could cause progression/mutation of the disease. Any idea why they don’t accept this new research?

I think most oncologists who are clinicians only and not researchers wait until a new practice is approved by an advisory group.  The researchers who spend some time in the clinical setting with patients like us are the ones who make up the advisory groups and are more comfortable with new approaches to treatment.  And it's probably a lot easier for the clinicians to just stick with what they know until they know something new.

Here's a recent piece from Haematologica:

Precision tyrosine kinase inhibitor dosing in chronic myeloid leukemia?

Giuseppe Saglio, Carmen Fava and Robert Peter Gale

Department of Clinical and Biological Sciences of the University of Turin, Mauriziano Hospital, Italy and Haematology Research Center, Division of Experimental Medicine, Department of Medicine, Imperial College London, UK

"The bottom line is that it is time to re-think our strategy
of using TKIs to treat CML. We suggest testing an individualized,
precision-based approach that considers disease,
patient and therapeutic goal heterogeneities, and
modifying therapy according to the rate, depth, duration
and stability of molecular response while acknowledging
poor correlations with EFS, PFS and survival. Much work
remains to clarify these issues, and this needs to be tested
in randomized trials."


Your doctors are 'ignorant'. Low dose does not cause mutations. Low dose may or may not work depending on "you" - the patient. You are unique. Finding the correct dose is what matters.

You have to keep in your mind that your doctors are licensed physicians who are at legal risk if they depart from established protocols. But, they are also expected to keep learning. Eventually, enough doctors will be applying new protocols that by NOT giving you dose modification, they could be guilty of malpractice. It takes time. Your doctors do not want to 'risk' being out of the mainstream of practice. I can appreciate their concerns given our litigious society - but that doesn't mean they are practicing medicine with you front and center. In the back of their mind, liability is a big concern.

Research oncologists, however, have a different motivation. They want to be famous! Discovering "new", being "first", setting the trail, is their motivation. They are the ones who publish papers by the bucket load. They are sought out for their "opinions" and advice. In the clinic, they want to apply what they have learned first before anyone. They tend to be very smart people.. And arrogant. I like researchers. They lead in clinical trials where they learn (even if the trial is a "failure") what may work and not.

And then there is "US" - the patients who live with this disease. We know the most - collectively. We really do. On this forum and elsewhere, we learn from other patients what they have done, seek to do and who their doctors are (both research and those who practice). We have access to the full range of debate, approaches and what has / has not worked for them. We can't "sue" ourselves by trying something and it doesn't work. We have to be our own best advocate and use the professionals as advisors. In some cases we know more than them (like you now know more about dosing than your doctors). To be honest, my doctor is now just a lab tech for me. Take the blood samples, run the tests and give me the results. I'll take it from there. If something strange turns up, I'll seek an expert 'in that area' - who....publishes papers. And if I benefit from this new experience - I'll share it .... on this forum.

You could try pointing your Doctors at Prof Richard Clark's papers on the Destiny Trial in UK, to back up the link to the USA work Scuba & RC have posted. The trial involved cutting standard dose in half for 12 months and if MMR was maintained medication was then stopped, and many achieved TFR.

I am now nearly 6 months in to trying TFR following the Destiny Trial protocol, under the care of a consultant at the hospital in Chester (whch is in England), despite the fact I now live in Wales. At the patient day in September I talked to Prof Clarke about this, and one of his comments was that NHS in Wales was more likely to wait for guidelines to be agreed and published than in England. The guidelines had not been published when I started (I believe they have now), so if I had not stayed with the consultant at Chester when we moved to Wales, I might not have been supported in following the protocol 18 months ago. It probably also helped that my consultant in Chester did some of his training in Prof Clark's team in Liverpool. The point about doctors who are not specialists/researchers in the condition being conservative and risk averse and therefore slavishly following guidelines is well made

Hope this helps

Brilliant, Scuba! Right on the money! Love this post!!!!

I’ll be 64 this year so I took my onc a copy of study finding lower dose Sprycel better than higher dose for elderly. He scoffed and would not even look at it b/c he had already lowered from 100 in Jan (off entirely in Feb) to 80 in March, then 50 in April. He argued we are going too low too fast and wants me to stay at 50. To treat my “fatigue” he offered Ritalin (Lol) and actually tried to pressure me into that. Today he had to stop my 50 due to still too low CBC, going barely up and back down. Second time I had to stop since Jan.
He just won’t go to 20. I’m thinking of writing a waiver of liability letter and insisting he let me decide my own care.

Sarah, you didn't say what your level of CML response is.  It could be your onc is trying hard to get you to a deeper response level before reducing the dose again.  Some are comfortable with just getting to MMR, but put me in the camp that thinks it's safer to get much lower than that before monkeying around with super low dose Sprycel (i.e., 20 mg).  However, if you are already there, I can readily understand your frustration. 

On the fatigue, your onc is not coming out of left field on the Ritalin.  If you research Ritalin (or Adderall) in cancer fatigue (usually other kinds of cancer than ours), there is some literature to suggest it helps.  I considered it once, but finally was swayed by someone who takes it that it offers a different kind of "feeling alert" than what we lack.  Anyway, just wanted you to know your onc isn't blowing you off with that offer of help. 

You might be able to sell him on 20 mg with the concept that it's more important for you to stay on a TKI at a very low dose with no more breaks than it is to keep trying at a higher dose and having to come off for a period of time.  Don't be averse to switching TKI's, also.  Finally, are your CBC numbers truly so dangerously low that you couldn't ride them out for awhile?  For most of us, they rise eventually, all on their own if we can just be patient.  I'm doctoring from afar here and with no license!  


You wrote,

"... It could be your onc is trying hard to get you to a deeper response level before reducing the dose again.  Some are comfortable with just getting to MMR, but put me in the camp that thinks it's safer to get much lower than that before monkeying around with super low dose Sprycel (i.e., 20 mg).  However, if you are already there, I can readily understand your frustration."

It would be a mistake to assume more drug leads to deeper response. Research is showing in the case of Dasatnib, that it is probably BETTER to start with lower dose than the current standard. In other words, low dose dasatinib is more effective in driving CML to deep remission than higher dose. Here is the research article:


I know this sounds counter-intuitive - but not all drugs behave the same way in the body. Imatinib is much more a dose dependent drug. Dasatinib is not. It is more of a threshold drug - meaning, one has to find the correct dose that works and once that is found, more drug may actually lead to a poorer response. So as the article pointed out, starting lower and working up is a bona fide strategy in these cases.

It certainly worked in my case. I had a much better response at 20 mg vs 40 mg and could have died at 70 mg. when severe myelosuppression set it. I became PCRU only when taking 20 mg. In other words, if I started to take more dasatinib (i.e. 40 mg), I could actually lose my PCRU status.


Scuba - I must not have been clear.  I meant that, absent a good reason (like serious side effects) it's better to let the TKI do its best and fullest job, getting you as far down as possible, before debating dosage reduction.  Starting doses for Sprycel have, as you know, started edging downward.  But whatever the dose you start on, ABSENT ANY REASON, you should give any TKI plenty of time to get you as far as you can go before worrying about reducing dosage.  First control, then reduction.  I stand firmly by that.

Kat - and my point is that in order to get "control", starting at a lower dose (only in the case of dasatinib) may actually give a better and deeper response. There is scientific research to back this up (cited in the paper I linked to earlier). I know it seems counter-intuitive (i.e. start with more to get bigger response), but the biochemistry of dasatinib has impact other than just CML reduction.

I know that study.  I don't want to get into an argument, but the variables of BSA (body surface area) dose adjustment (which is what they were studying), plus, I believe, no indication of whether participants with DLE's (dose-limiting events) had to completely stop dasatinib, thereby affecting the rate at which they reached or did not reach MMR weaken this study for purposes of proof that less is more.  I know there are a few more studies out there that touch on the phenomenon, and I myself have anecdotally observed that many people (me included) seem to take a significant plunge downward after a drug holiday and a return to a lower dose of dasatinib - all counterintuitive, your'e right.  But I have to wonder where more confirming studies are, and more pragmatically for us, why there is very little acceptance in the clinical world or the upper reaches of the research world for the conclusion that 20 mg of Sprycel should be routine.  Or that the best way to administer TKI's is to start low and go higher.  Or that 20 mg of Sprycel is even better for you than 50 mg of Sprycel.  These views may be vindicated in the future.  But I worry about the CML patient world fixating too much on lowering dosages just to lower the dose, as if this medicine were horrible for you.  IF you are not bothered by side effects (and that includes all your bloodwork), then I think you should be guided by your onc and the current established dosages.

Kat - Debate is good and useful. Everyone reading gets to see the many sides of how treatment decisions are made and learn what may be best for them. There is no one correct answer. But over time, consensus does seem to emerge. Treatment free remission was thought impossible ten years ago and doctors strongly discouraged patients trying insisting resistance will develop and progression will occur. The high cost of TKI's is what spurred on these trials! And to the surprise of many - it worked. Treatment free remission (as well as lowering dose) is becoming a standard option for some.

The title of the original thread, "Looking for resources to aid discussion about lowering dose of sprycel" is what prompted me to post some resources. It really is up to the patient and their doctors to decide best course. In my case and in yours, lowering dose led to a better response and lower side effects. There is evidence that a lowered starting dose (dasatinib) may actually lead to a better outcome with deeper response.

Keep in mind, all TKI's are toxic man made chemicals. We don't know the long term effects these drugs may have later in life. This is especially true for the second line treatments (dasatinib, bosutinib, et. al.). Lowering toxicity levels can be a worthy goal in its own right for this reason alone. As long as the drug works at the lowered dose and the trend is down. Finding the correct dose should be part of the protocol. That will happen.

At least on this forum people get to read pro's and con's long before it gets to the mainstream. It's too bad they don't get this from their doctor so an informed decision can be made.

Well-said, Scuba, and you certainly get an Amen from me about many of us not getting a whole lot of info from our doctors.  

I wonder if we could maybe use the word, "problematic" instead of "toxic" to describe our meds.  That would make me happier.  But I certainly worry just as much as anyone else about the longterm effects.  TFR or a functional cure are what we're all after.

In the meantime, we have each other and everything we bring to this forum.

Hi Kat73,

My response for 7 years on Imatinib hovered between 88% and 32% (IS), till mutation was found in 12/18. I changed to Sprycel in 01/19. First month 100mg, dangerous suppression. Off for second month. Third month 80mg and PCR was .0542, (nearly 3-log reduction!) but again had to come off for another month. Lowered to 50. 

Now just came off 50, b/c still too high. Next PCR will be in June....  (?)...  I’m not on anything again, waiting to recover. 

Meantime, I’d rather be steady on 20, not on and off like Imatinib which ended in mutation. 

I showed my doc Scuba’s study in Feb. Then in April I showed him a study finding 20 is better than 50 or higher for elderly on Sprycel. He would not read either article but offered me speed. No thank you  😞. 


"He would not read either article but offered me speed. No thank you"

.... what does that tell you about these kind of "doctors"?

Your sprycel response was very similar to mine. Other research has shown that those who have 'severe' myelosuppression are very good candidates for very low dose. It simply means their cells are very sensitive (including leukemic ones) to sprycel. My doctor did not waste any time when he saw this - he immediately put me on 20 mg after a drug break (i.e. no stim shots of neupogen!). I have been on 20 mg ever since and have been PCRU for two years. Looking forward to TFR.

What's sad to me is that there are patients who are being 'forced' to take 100 mg of sprycel who have "o.k" response, but who would likely have a much better response - deeper and perhaps permanent remission - if they were on a lower dose! Some day this will become protocol. Right now it is up to the patient to find the doctor who knows this.

Hi Sarah,

Am I reading correctly that your PCR scores never got below 32% while you were on imatinib?  I'm surprised you were kept on imatinib for so many years with such a high PCR!


Actually, at one point I got down to 11%, but... still... yes. And I am a lot to blame, I was not diligent with compliance. Also my doctors (two different ones) did not share the info on milestones (I don’t think they knew it, neither was a CML expert) and I placed my attention on CBC white blood cell count. It was really only after I joined internet groups of CML people that I got educated, and just about that time i developed a mutation for being so sloppy with Imatinib. I never miss a dose now. That scared me big time.