I understood that if a CML patient was on too low of a Glivec dose that it could lead to a resistance. I'm now trying to find where I found this information
I am still new to CML as a carer and was wondering if anyone could point me to some resources to confirm my understanding, or alternatively, correct me if I am wrong.
Thank you
Michelle
Dear Michelle,
It's true that too low dose of Gleevec may lead to resistance. That's why some CML patients who have only minimal residual CML which is not detectable elect to stop taking the meds altogether - instead of further lowering the dose.
I've discussed this issue with my son's oncologist (Dr. Brian Druker - doc who discovered Imatinib). Since my son is only 10, I asked whether he could be maintained long term on low dose Gleevec. Dr. Druker said that he wouldn't go below a certain dose because of risk of resistance.
Dr. Druker is investigating what actually causes resistance and future studies should explain why it happens. For now, it just does happen.
Hope this helps.
Regards,
Tracey
Hi Michelle,
the recommended dose of imatinib for chronic phase CML is 400mg. If this is well tolerated and the patient takes the drug consistantly there is every reason to be confident that they will see an optimal response...i.e HR within 3 months; CR at 6 months CCyr at 12 months. However some patients are slow responders and may take longer to achieve the desired goal of CCyR (complete cytogenetic response).
However, a small % of patients do show some form of suboptimal response and a further % do fail to show any response at all.
A sub-optimal response (note that this does not mean failure to respond)is apparent in a small number of patients and there can be several reasons for this.
a. Adherence... taking the drug every day and not taking 'holidays' now matter how good your pcr ratio is.
b. some form of drug to drug interaction (if other medication is being taken) and/or food interaction which cause incomplete absorption.
c. individual pharmacokinetic profile... which means that you might need a higher dose than standard for reasons peculiar to your individual metabolism.
Adjusting the dose can and often does solve sub-optimal responses.
resistance:
it is thought that if you take less than 400mg you may have a consistantly low plasma level of imatinib (less than 1000 ng.per mil) with the risk of assisting some sort of resistant mechanism.. whether it be a breakpoint mutation or futher clonal abberations, amongst other things, within the ph+ cell.
If resistance is identified there are other TKI's that are now available for such patients.
If you read some of the articles under the Newswire section or under News and/or essential reading you will find lots of information.
Do read the Leukaemia Insight Newsletter from MDACC... again under newswire and the excellent webcast by Jorge Cortez called Monitoring and Adherence in CML.
Sandy
