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Every Other Day Dosing vs Daily Sprycel

Hi there

I’ve been off Dasatanib for 2+ weeks now waiting for neutrophils (now recovered) and platelets (up to 42 as of today) and Dr. mentioned restarting at an every other day dose or an every day at 50mg dose once platelets are at least 50 but ideally 100). My preference is strongly for every day at 50 (or lower) but I don’t want to push for this if there is any advantage to every other day.  
 

does anyone have any experience with this?  
 

thanks!

Renee 

My doctor did not recommend every other day given that dasatinib's blood level half life is only about 5 hours. He believed (and I concurred) that every day lower dosing vs every other day higher dose enabled dasatnib to do its job. It's simply too many hours off drug every other day.*

In your case, you are much better off (strictly my opinion - discuss with your doctor or seek a second opinion) re-starting dasatinib on 20 mg. You are very sensitive to dasatinib which is a good thing because your cml cells are 'sensitive' to it too. You are very likely to respond quite well to lower dose, you will likely avoid severe myelosuppression AND you will be exposed to much lower toxicity. You can always increase your dose if you don't achieve a response trend downward. You have time - that is what is key here. As long as you are in chronic phase (i.e. few to zero blast cells), you have months to get this right. Your doctor should know this.

Right now, your goal is to get a normal blood system established on some level of dasatinib therapy. No sense screwing around with high dose that doesn't work until you get stable. Then, if necessary, you can increase dose as your blood system adapts. Think of it this way - you have been off dasatinib for two weeks! How much better to take a lower dose and have some drug in your system fighting CML while avoiding myelosuppression.

There is no guarantee that lower dose will avoid myelosuppression. You may have to switch drugs. But I strongly believe that you are very likely to adapt and succeed. You just have to try. It will likely take months, but the trend should establish within weeks.

*(I do take 20 mg dasatinib every other day - my choice - but only because I have been 'undetected' for over two years and I am getting ready to stop altogether. I am testing whether my CML becomes detected again at next PCR (March). If not - then I will stop therapy and test cessation. This is my personal experiment - no doctor recommends every other day for 'detected' patients.)

 

Hi scuba,

I was really surprised about the every other day idea at this point.  I won’t even have a PCR test until late February at least.     I am really pushing my Dr for 20mg and frequent checks and so far she is amendable but not convinced. We will talk about it again after next CBC next week.     I’m working on it :) and brought up your point about not being on ANYTHING now so why not 20mg and keeping close watch?   I also stressed with her the mental toll not being on anything is taking on me.... In the meantime I will see Dr Mauro for a second opinion. 

I really like my Dr but she is being more conservative and prefers starting higher (50) then moving to lower doses after PCR shows efficacy and only if side effects call for lower dose.  I’m happy that lower dose is her solution before switching.  For some reason I’m probably more invested in Sprycel than I should be and don’t want to move on to other TKIs until I’ve exhausted this one.  Is that silly thinking?  

 

Also, thank you. I really needed some hope today.  Being on medication holiday is making me very anxious.  I really like the idea of getting a normal blood system established on any dose of Sprycel.  That makes a lot of sense and I’ll use that in an email I’m about to send to my specialist.  

Tell your doctor that Dr. Jorge Cortes, one of the top 4 or 5 specialists in CML research and now is the director of the Georgia cancer center (U.S.) is the one who prescribed 20 mg to me and told me that since I had strong myelosuppression, that starting low and working up (if needed) is the way to proceed. That should give your doctor some measure of confidence. I did not come up with 20 mg on my own. I was guided by an expert. I am sharing what I have learned and experienced with you. Share what you have now learned with your doctor.

All she needs to do is monitor you! There's no mystery here. You should be having weekly CBC blood tests (to track blood counts) and monthly PCR checks to verify response. When you start 20 mg dose, within a week you will know if myelosuppression is still an issue. If it is, you stop and monitor blood counts. Then re-start again when blood counts recover and monitor. You may have to do this two or three times, maybe more, hopefully, no more. But once you stabilize (i.e. neutrophils or platelets stay above critical, but may be below normal), you will continue taking your low dose. Then in one months time, you test PCR (or FISH depending) and compare to previous level. If PCR dropped - you should dance and have wine and celebrate. You have arrived. Then you continue 20 mg as YOUR personal treatment dose. This is what happened for me - so it's possible eh?

Now then - if your PCR doesn't drop or instead rises, you can move to a higher dose at 40 mg. You may experience myelosuppression again, but likely not as severe (remember, your normal blood system is continuing to recover while your leukemic system is getting strangled and can't compete). And if myelosuppression is severe enough to stop therapy, restart back at 20 mg. Your priority goal is to get your normal blood system adapted first while continuing to have some dasatnib in your system. As long as PCR is stable during this phase you are good. And if on 40 mg you test and no severe myelosuppression and PCR in one month's time is trending down, 40 mg is your dose. I doubt it will be higher - maybe 50 mg, but not likely any higher than that. 100 mg is out of the question - that's toxic for your personal situation (toxic = myelosuppression and related).

This is not rocket science. I wish doctors worked with their patients based on what is now known about CML. You are likely learning more about CML in your particular case than your doctor knows. Think about that. All she has to do is work with your personal situation. We KNOW CML is slow in chronic phase - this is why the new standard for pregnant CML patients is to stop therapy and tolerate PCR rising while the pregnancy is taken to term. There is NO case I know of where a pregnant women stopped therapy in order to have her child, did not successfully resume treatment post pregnancy). That's NINE MONTHS. So, tell your doctor, imagine you are pregnant - what would she do? You know the answer. You have nine months to get your dose right. I have a strong suspicion you are going to do great on 20 mg.

Note: if your doctor tells you she is concerned about "resistance" developing at such a low dose, get a new doctor. CML is not a bacteria or viral infection.