23 replies to this topic

[jjg]

Hey Pin 0.01 is a pretty nice number. Did they look at the drug transporter protein OCT-1? I know very little about it but it was mentioned as something they might have tested in me because they were looking for a fast response but because I had a fast response they didn't bother testing it, if that makes sense. When I was on 600 mg glivec my trough level was around 1000 ng/ml. I was surprised because I'm not a big person and I seemed to be having plenty of side effects on 600mg, I also had a fast than average response even with the average trough level. The trough level is just what ends up in the blood, it's not the full story as you want to know what ends up in the cells (suspect that the OCT-1 thingy tells you that). How much gets to the blood would affect how much gets to the cells but you may have super glivec loving cells. I'm guessing you don't really want to increase your glivec dose?

[Trey]

BMB, FISH and PCR provide directly useful information about response to TKI drugs.  These other things such a blood plasma trough levels and other such tests should be viewed as fuzzy science.  The trough levels could vary for many reasons, some good and some not so good.  For instance, if your uptake into the WBCs is very good (Gleevec is taken up via hOct-1 transporter, but Tasigna and Sprycel are not) then your trough levels might drop lower than someone with poor uptake.  If that is the case, then your plasma levels could be lower than someone with poor uptake.  Plasma levels do not fight CML -- only TKI drug inside the leukemic WBCs fights the CML, and no other place.  Of course, the drug must be delivered by the plasma to the cells, but drug plasma level is still an indirect measurement.  So plasma levels should only be viewed as a piece of a puzzle, not useful information by itself. 

Since Gleevec is taken up into WBCs via hOct-1 transporter, but Tasigna and Sprycel are not, this is one reason why the second line drugs work better for some people, since we all have different uptake capabilities, first from the alimentary canal, and secondly from the plasma.  There are other differences among the drugs, and this is why switching drugs is often a good idea any time response is sub-optimal, even if it is just to see what happens, better or not.  But since your response is fine, any drug changes would be a personal choice based on side effects profile or just because you want to try another drug to see what happens with your PCR.

[Pin]

Thanks so much everyone - this is all really helpful information.

Gerry - the side effects are pretty much the same as they've always been, pretty annoying, sometimes awful - but I can generally stand most of them, for most of the time. I do think that all of this has a likely link to the herbal stuff. I don't want to get into details, but my digestive system is only now getting back to what it was pre-supplements, probiotics etc. So, I think it really is possible that they have been affecting me for that long (it's been several months now since I stopped). We really do not know enough about interactions and a lot of this stuff is so individual anyway so I am definitely avoiding anything like that from now on.

Josie - you are absolutely correct, I am not at all that interested in an increase in dosage - partly because I think it is unnecessary given what I currently know, and partly because I have a pretty strong feeling (based on other people's experience as well as a gut feeling!) it will  increase my current side effects. Hopefully no new ones, but you never know - my platelets are only ever just 'normal' ish, they bounce in and out and I think that is something that could take a hit if I increased. I already bleed all of the place from any old little cut or graze.

Trey - thanks for this explanation - I had a hunt around for information about trough levels and there wasn't much I could find, except that the cut-off of 1000 had the best sensitivity/specificity for predicting MMR. Which seems kind of redundant here. I do think a lot about your theory of maintenance at a lower drug level though and how this might relate, but perhaps as you say - this is more to do with uptake. What I'd really like to know (but can't) - is have these levels changed significantly. If they haven't really, then it doesn't matter at all - response is response. But if they have - then something is getting in the way. Not an answer I can find unfortunately!

Anyway, thanks again everyone - so grateful for this group

[GerryL]

Hi Pin,

I don't mind a supplement or three, I just avoid anything to do with the liver.

Have you tried keeping a bit of a food diary for when your stomach issues hit - I found coffee to be a bit of an issue, though it wasn't every cup of take away, just some of them. Stress maybe another thing adding to the issue.

I'm not sure if you've stopped everything, but the probiotics are okay to take.