7 replies to this topic

[BPilgrim]

I am trying to decide if I should go from 400mg down to 300mg Gleevec, based on my 1260 ng/ml Gleevec blood level.  One of my main concerns is drug resistance, and I was able to find a few mentions on the internet about lower dosages possibly leading to resistance.  Has there been any recent data to support or refute this?

Also, has anybody gone from 400mg to 300mg, and did they notice a side-effect difference?

Thanks as always.

[Trey]

Regarding the issue of Gleevec dosages below 400mg, the thinking seems to be changing slowly.  A few years ago the leading Oncs were expressing concern about dosages below 400mg causing drug resistance.  These same Oncs have recently been softening their statements on that issue.  The NCCN Guidelines recommend dosages below 400mg for low counts and other severe side effects.  Dr Druker has said he is OK with lower dosages for those with low level disease as long as they maintain a minimum Gleevec plasma drug level of 500 ng/mL.  Since 400mg will generally provide most patients with 1000 ng/ml or higher, you can do the math.  But recall, the Gleevec absorption rate differs in each person, so Dr Druker recommends Gleevec plasma level monitoring for lower dosages.  A couple years ago Dr Shah (in a speech in Canada) said that he was rethinking the issue of whether lower dosages could cause resistance, since it now appears that the basis of resistance is probably there from the beginning stages of the CML and not caused by a lower dosage (paraphrasing).  This is shown by the fact that most drug resistence happens within the first year or two after diagnosis as the low level resisting cells grow slowly over time to detectable levels.  That is why the leading Oncs say that if we make it through 2 years without drug resistance, then it will likely not occur after that (but there are always rare exceptions).

There is another way to look at this issue logically.  The issue of drug resistance is best shown by antibiotic drugs.  Most of us have taken antibiotics, and we were always sternly warned to take all of the pills in the bottle, even if we feel better.  The reason is that the antibiotics kill bacteria, and and if we only partially kill a bacteria (only take partial dosage), then that bacteria can survive and grow stronger and learn how to overcome that drug.  That is why antibiotics must constantly be changed and new ones invented, as bacteria becomes resistant to the old antibiotics.  But Gleevec does not work in tha same way to kill leukemia cells.  Gleevec will simply latch onto a docking port that the leukemic cell needs to use to proliferate and survive.  By occupying that docking port, the leukemic cell is shut down.  There is no partial shut down.  It is either turned off or it is not.  So logically it does not appear that typical drug resistance is likely to occur for these TKI drugs.  Additionally, because we cannot take enough drug at first to shut down all leukemic cells, one would assume that would cause resistance in the cells that only saw "partial" dosages, if the TKI resistance theory were true.  So the issue of resistance does not really fit the TKI drugs.  But most docs revert to what they have seen drugs do in the past, so they are cautious about this issue until proven otherwise.

[BPilgrim]

Trey, thanks for the reply. 

Do you know why Dr. Druker is okay with the minimum 500 ng/ml level?  Didn't it used to be 1000 ng/ml?

[pamsouth]

Thanks Trey,

Doing Happy dance.  I have trying been trying to put that all into perspective, but seems like I have been on a merry go round.

I do believe your statement would be an up to date, 2012, concurrence with the leading CML specialist.

PamSouth

[momruns]

I did post in the past regarding my dosage.  I was dx in Feb 2011.  Started on 400mg/qd then 4months later put to 300mg and in March of this year I was put to 200mg.  I had a 3 log reduction on my last blood work.  Since I am on 200 I have been getting blood work every 2 weeks.  My ANC is still a little low at 1.4 but everything else is good.  My WBC has been stable at 3.1.    I know there is a lot of discussion regarding reducing dosage and some are really against it.  My onc is the CML expert at the regional cancer center I visit. 

    If my BCR-ABL and ANC stay stable I am blessed to be able to stay on this dosage.  This was not a decision by me, it was a joint decision by myself and my ONC.  I am a nurse but not in oncology.  I have read Trey's information for which I am very grateful he posted this. 

Best of luck to you and keep us updated.

Loreta

[pamsouth]

Momrun,

I so appreciate your post.  I hope you retain your 3 log reduction.  Do you know what range will be acceptable before your onc would prefer you went back on 300mg?  Where or who is your oncologist? 

Humm ANC what is normal range?  How long has yours been low? I would think on 200mg it would come back up, or is that going to be a permanent thing.  See that is what I have been trying to watch on this board??  On these side effects of TKI's what becomes permanent damage and could they have been avoided on a lower dose.

Sometimes I hate to post as some, are so against lower the dose, thinking they will live longer, or they will have mutations.  I can't imagine get upset over a .001 to a .01 or whatever!!  I think the fear of just being diagnosed, especially new people, some doctors scare the BG'S out of you.  The unknown is scary. Not that it isn't serious disease, but is it really necessary to take such drastic measures, then have all these other additional health issues.  TKi may be a targeted drug but they are still very toxic to the whole body.

I think it is even more important to stay at the lowest dose you possible can, as to give your organs a rest and to function as normal as they can.  Chemicals take such a toll on our body, if not now, long term side effects could leave us with a poor quality of life.  I not in a hurry to die, but not much fun when you have a lot of limitations. I mean you take one drug for something then you have another problem, then you take another drug and it gets to be a vicious cycle of juggle meds, labs, side effects and your whole life becomes about cancer.  Not only that but even if you are undetectable you still have millions of CML cells.  So I have come to the conclusion that the lower the dose and keep your CBC counts to as close to normal as you can while keeping the CML counts in a stable range would be the most I could hope for.

I can only dream of being on 200mg of Gleevec.  I recently changed onc and have only had one lab, it was not that I would be able to lower dose.  My previous onc sent my blood labs out of state for 6 years and I was PCRU until last year, but it turned out the lab had changed over to the IS.  In fact it was me calling the lab and LLS as my doctor was freaking me out to change drugs.  Mind you had been on Gleevec for 6 years.  To my knowledge it was not anything that had changed regarding my CML or Gleevec but the lab testing.  So I was not near as upset as my onc was.  Anyhow I found out that INdiana Univ Cancer center does there own labs and interpretation.  I have only had one set of labs the next labs are not due until June.  Hopefully I will remain in a stable range.  I am not overly concerned to be PCRU as long as the numbers are stable.  I recently went to a seminar and the onc said it is OK to even have labs in a wave, as you can have 12 different labs and 12 different results.

I am anxious to see how you do on the 200mg.  Wow 3 long reduction in 4 months.

Best of wishes, PamSouth

[momruns]

PamSouth,

Just a few things, I did not have even a one log reduction for almost one year and then boom 3 log reduction this last time.  It has been 1 year and 2 months.  I go to the Regional Cancer Center in Erie Pa.  They seem to follow the recommendations of MD Anderson.  My FISH was a little odd this last time and he said everything is right were it needs to be but the FISH is only done because they recommend it.  As for the ANC, this level should be above 1500 or 1.5.  When mine hits 1.0 or 1000 they call stop my meds for a week and tell me to watch for signs of infection.  I usually am 1.3-1.8.  I am a nurse but I am blessed to work in the operating room.  I gown, double glove and mask each day.  If I worked on the nursing floors it would be different with all the germs floating around were I would be in close contact with patients.  The OR is were I can work and stay healthy. 

We will see.  I get blood work next monday again I will update you.  Take care and stay healthy.

Loreta

[pamsouth]

Momruns,

Hum.  was interested in your comment "FISH a little odd"???

In the past I have been undetectable/PCRU, while by FISH might have been at 1%  positive.  I sometimes have the b3a2 and the b2a2 positive.  Sometimes I wonder if there could be some kind of cross over, I don't really know what I am saying.  I just picked that parts of a conversation up  from another post, I didn't understand it, but it was pertaining to my post about have a positive FISH and a PCRU.   Some of the post are from patients who have lab/science degrees.  Glad to see them on here, but sometimes I get lost, but I keep trying.  I think I spent to much time on here.  I need to exercise.  But since I have changed onc and the push to change to a newer drug and to understand the new theories on lower drug dosage and where mutations start and all that.  Well I think it is important to understand so you can be your own best advocate.  Doctor are only human and CML and Drugs treatment interpretation vary form different doctors and different drugs and different patients.  I find a wealth of knowledge on here.  An oncologist nurse told me she thought these post were a bit skewed because when someone has a problem they post then everyone jumps on board.  Next time I talked to her I had a chance to think about her statement.  I said the patients on this board;  are very intelligent people, and some working in the medical field and biology/science and all.  Well not only do they understand the nuts and bolts, but being patients they understand from my perspective, they really, really, get it!!

My new doc said he didn't know how that could be so he ran some genetics and nothing of concern, only the BCR/ABL nothing else.  I asked him why run a genetics, he said because when they do the FISH and PCR they only look for BCR/ABL, and he wanted to look for other things.  So I guess he went a fishing, lol.  Lucky me nothing else showed up.

Anxious to see how your labs from next Monday turn out.

Glad you are still able to work, we need our nurses, they are the one we really count on.  I should clarify that.  All are important, but I have learned for taking care of my mom for 3 years before she passed.  You can have a good doctor and he can do all the right things, but unless you have good nursing in your day to day care, it doesn't matter much if the doctor is any good.

Now tell me again how you did your own blog.  I read part of it.  Thanks for sharing.

Pamsouth