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How does dose reduction reduce side effects?

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#1 kat73


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Posted 08 February 2016 - 06:03 PM

It sounds simple:  take less of a drug and you will get less impact from its side effects.  But if you think about it, why would this be so?  When you lower the dose of your TKI (after first having been stable at a low level of CML for some time, of course) you assume it will still have the same effect as a high one, right?  I mean, it hits the baddies just as effectively when it's thinned out, so to speak - otherwise, your PCR would show an upward trend, right?  So why would you expect the off-target hits to be any less at a lower dose?  They go right along with the targeted hits.  I'm probably not being very clear. 


I have a visit coming up and this is just the kind of question my onc does NOT ever want to talk about.  He gets mad at me instead.  And this visit I really, really want to talk rationally about finding a way to stop taking this drug soon, so I need cool-headed ammo.  He is very opposed to reducing dose, on principle.  But he definitely wouldn't let me quit altogether outside a clinical trial.  So I'm trying to see if it's worth it to go to battle over dose reduction.  If it could make a difference in the SE's, I would settle for that.  But I just can't see the logic.  Can anybody explain what I'm asking about?

Dx July 2009 on routine physical.  WBC 94.  Started Gleevec 400 mg Sept 2009.  MMR at 2yrs.  Side effects (malaise, depression/anxiety, fatigue, nausea, periorbital edema) never improved.  Kidney issues developed because of Gleevec.  Switched to Sprycel 70 mg in Aug 2011.  Above side effects disappeared or improved.  Have been MR3.5 - 4.5 ever since.  Two untreated pleural effusions followed by one treated by stopping Sprycel Jan 2017.  After 9 weeks, PCR showed loss of MMR; re-started Sprycel at 50 mg and in 3 months was back to <0.01% IS.  Pleural effusion returned within a couple of months, same as before (moderate, left side only).  Stopped Sprycel 50 mg for 12 weeks; pleural effusion resolved.  At about a monthoff the drug, PCR was 0.03; at 11 weeks it was 2.06 - lost CCyR? Have returned to 50 mg Sprycel for 3 weeks, intending to reduce to 20 mg going forward.

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