9 replies to this topic

[holygeez8]

I was diagnosed with CML in May 2012. My doctor put me on Sprycel first, but I couldn't take enough to get a good response. I have been on ponatinib, 30 mg, since December 2012. It works for me. I have achieved PCRU a couple of times and have been less than 1% since Feb 2013. My doctor wants to change my drug because of the effects of Ponatinib, but I have reservations about this. We talked about doing bosatinib(sic), but now he is leaning towards Gleevec. I don't have any mutations. Any advice?

[Trey]

I assume he wants you to change because of the Ponatinib FDA warnings.  Personally, I would not change until continuously PCRU for over a year.  No real rules there, just what seems right.  I would think that switching to something else for the longer term is a reasonable idea.  If cost is an issue, a Gleevec generic will be readily available starting in mid-2016, and it could be an acceptable longer term maintenance drug for you since your issues were all about low blood counts.  Bosulif (bosutinib) would be OK but it inhibits SRC kinases which I would personally prefer to avoid for the longer term.  I would probably choose Gleevec and take 400mg for a year then reduce to 200mg for the longer term if PCRU was sustained.  But there is not just one answer, and continuous PCRU opens up several options.

[Tucker1]

Trey, what is the problem with Bosulif and inhibiting SRC kinases? I am taking it now 100mgs And I am interested in any information about Boslif.

[Trey]

Every TKI drug approved for treatment of CML inhibits secondary or off-target kinases (i.e., more than just BCR-ABL).  These off-target kinase inhibitions vary by drug, which is why changing drugs results in different side effects.  So we cannot avoid having off-target kinase inhibitions.  But these are generally not significant issues unless they result in a side effect which is significant.  Both Sprycel and Bosulif inhibit SRC kinases, and inhibition of SRC has been shown to increase the likelihood of pleural effusion, which can be debilitating when it happens.  So my point is I would prefer to avoid SRC inhibition because of this.  Although Gleevec inhibits off-target kinases, most of the side effects are not as significant, even though they can be numerous.  Dose reduction over the long term will eliminate most of them. 

 

The article below says that inhibiting SRC in CML does not appear to have benefit, although it does have benefit for Philadelphia Chromosome Positive ALL leukemia.  This is because CML is mainly myeloid blood cells and ALL is lymphoid blood cells. 

http://www.ncbi.nlm....les/PMC2063586/

 

Avoiding off-target kinase inhibition is not easy, because the drugs can fit into multiple kinase pockets which are similar even though not exactly the same.  A baseball glove catches a baseball, as it was designed to do, but a fishing net will also catch a baseball, even though less efficiently.  The reason drug manufacturers want to inhibit SRC is to be able to use the drug in multiple applications.  Inhibiting SRC has a role in several types of solid tumors, so inhibiting it to help treat those is useful, although that does not usually work well enough just by itself.

 

I would not be overly concerned about this issue.  I answered a question based on the person's individual needs.  That does not apply equally to everyone.  And unlike some here who constantly say TKI drugs are "toxic", I do not believe that is accurate at all.  For some people with certain specific medical conditions, some drugs need to be avoided.  And all TKI drugs, as with almost every type of non-CML drug on the market, have side effects since TKI drugs are not perfectly targeted.  Choosing a drug which meets your specific needs best is a luxury we have.

 

Inhibition of kinases in fighting cancer is less than 20 years old in its history.  Gleevec was the first major success in this field. There is still a lot to learn about the issue.

[Tucker1]

Thank you so much for such a complete explanation and the article I really appreciate your time and effort you give to help others navigate CML. Thank you again I seem to be in a spot now and I am searching for options and information.

[Billie Murawski]

I personally choose a couple glasses of white wine over tki's but we have to do what we have to do. My goal is just to get on the lowest dose possible and maintain pcr .

[holygeez8]

Thanks Trey

[Judithb]

Trey, and others:

 

Do you have any comment on switching from Tasigna to Gleevec after just 4 weeks becasue I cannot tolerate the "head on fire" side effect.  The Tasigna has been very effective in bringing the hematologic numbers down.  Of course I will see my onco about this, but would love some advice from others first.

 

And again, tks for being a guru for me and others.  Your post on how to interpret test results was a godsend for me and my husband. I have your blog book marked on my Mac.  Godbless.

[Trey]

It takes at least 3 months to minimally adjust to a TKI drug.  So I would not switch from any TKI drug due to side effects during the first several months. 

[Judithb]

Tks, Trey, as always.