What is the current thinking about patients having had pleural effusions on dasatinib switching to bosutinib? All that I can find in the literature is a couple of case studies that found those patients fared badly after the switch, with more pleural effusions. It's true that dasatinib and bosutinib both inhibit the SRC kinases, but I also read somewhere (can't remember the paper) that that wasn't completely dispositive, as pleural effusions could be caused by some coupling of SRC with other factors that are present in dasatinib, but not bosutinib. Anyway, bosutinib is about the last TKI left to me and my onc wants me to make the switch, after I reduced my dasatinib to 25 mg (50's cut in half) and STILL got another pleural effusion. Thoughts? INFO?
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Bosutinib and Pleural Effusions
This is a recent paper on pleural effusion management:
It highlights the use of diuretics to facilitate fluid reduction. Dr. Cortes is the lead author and prescribed my current 20 mg Sprycel.
Bosutinib (Bosulif) is very popular with CML expert clinicians in the UK. Unfortunately it seems to have been under prescribed - at least in Europe -because not only was it late coming to the fore but also the first c/trials showed the main side effect for most patients is diarrhoea and this was not managed well at first so trial clinicians stopped the drug- therefore it did not reach its main trial end points. Since then it has become very clear that this effect is transitory for most and can be easily managed. However it looks like the uptake of bosutinib is rising- we think because its side effect profile is less challenging compared to other 2nd Gen TKIs.
Yes, Scuba, I read that. The trouble is, the treatment with prednisone and diuretics for a dasatinib-triggered pleural effusion has not been well-studied, there is no protocol, and as in this article, has been met with a pretty tepid response by the medical team. What mostly works is a drug interruption. I only just got back on Sprycel at 25 mg and have not yet gotten back down to my previous <0.01 and I really want to give it more time. I'm going to see a pulmonologist with this question.
I am considering switch to Bosutinib and was wondering how you have been doing on it. Appreciate all advise and insights
I did not switch to bosutinib. I won the reluctant agreement of my onc to try Sprycel 20 mg. So far so good. The PE is extremely minimal - can only be seen on a lateral view, not from the front, and can't be detected by sound change (stethoscope). It has been stable there. No symptoms. Meanwhile, I have had 2 PCRs: one was 0.005 and the other 0.006. I'll be getting another one next week, so we'll see on that. I go back to the pulmonologist as well in a couple of weeks.
It is beginning to appear that the off-target effect that dasatinib and bosutinib share (the SRC kinases) is probably not the culprit in pleural effusions. It must be something else in dasatinib (PDGFR maybe) (which is a kitchen sink of a TKI - has everything in it!) That would explain why there seem to be fewer PEs on bosutinib. Bosutinib also seems better on fluid retention in general - gets good marks for facial edema, which dasatinib still has a problem with (again, probably PDGFR). I'm still clinging to the devil I know, however. We'll see how it goes.
My CML came whomping back, too, during the 12 weeks I was off to vanquish the PE. I even got back all the way to the left side of the decimal point, which was extremely depressing - I hadn't been there for 7 years! But the good numbers returned very, very quickly on resuming first 50 mg Sprycel and then cutting those in half. This is the experience most people have. It's just a little sad to think that I'm probably never going to be in the TFR cohort. Oh well.
Thank you so much for your quick response. I’m glad the 20mg is working well. I have been back on 20 for about 2 weeks and have PE symptoms - shortness of breadth, difficulty climbing stairs, etc. Not sure if I should simply continue and hope with more exercise I could condition my lungs or make the switch. My Onc does not have the right experience with this. Going to Dana Faber for a second opinion.
Given how well Sprycel has worked I am so reluctant to switch and keep hoping there’s some way to tolerate it.
Chigi - Don't ignore the symptoms; get them checked out. You just need your general practitioner to listen very LOW down on your back, to make sure he/she doesn't hear the characteristic diminished sounds of PE - most times, they don't listen past mid-back and it can be missed. Also, if there is something heard, get a chest x-ray with lateral view. That's all you need to find out if your symptoms correlate to a PE, and how extensive it is if it's there. Here's the takeaway, however: the PE, if it's there and it's caused by Sprycel, will not go away without stopping Sprycel. Diuretics and prednisone can really help, but only if you also take a drug holiday at the same time. You might still be able to come back on 20 mg, like I have SO FAR (don't anger the gods, I say. . .)
Chigi - Yes, indeed, good luck! They never made me undergo a thoracentesis, although I know of others who had it done. I was just suspended from dasatinib for a couple of weeks and the chest x-ray done again to confirm that the PE was going away. Then I was kept off dasatinib until it was gone (I forget the interval of re-checks/x-rays). Once I also took diuretics and once I took prednisone (I've had four PE's). I've heard that Bosulif is rough in the early days, but that a great many people feel it's "the best TKI for side effects I've been on." So, good luck on that, as well. Keep us posted, OK?