26 replies to this topic

[pennyarizona]

Hi,

I have posted a discussion on here a few days ago about having really bad leg problems to the point where it was hard to walk.

Well my oncologist took me off my Gleevec for one week.  My legs are still bothering me alot but have had some improvement.

So my oncologist wants me to stay off it for one more week making it a total of two weeks.  I'm a little worried because I don't

want to go through all the beginning side effects that were there in the beginning when I very first started G.  Has anyone else

gone off G for two weeks and then started it back up again?  He may have me go to 300mg instead of the 400mg.  That's another

question I have.  Is 300mg going to work as well as the 400mg but help with the side effects?  I really don't want to try one of the other

medicines that are out there.  Gleevec has made it to where there are no signs of the leukemia in my blood.  But on the other

hand its killing my legs.  Anyone else taking 300mg and doing well?  Has anyone ever been off G for two weeks and then started

up again?

Thanks for listening,

Penny

(UPDATE)  9-28-11

Hello,

Gosh I can't believe it's been over a year now.  Well as I mentioned above so long ago, gleevec really messed up my legs.  I went to a pain specialist, neurologist, the mayo clinic, and even a muscle specialist.  All any of them could tell me is that they believed it was "muscle toxicity".  Doctors are always so careful on what they say.  My legs got so bad that I ended up in a wheelchair in Aug. 2010.  After doing physical therapy for about 7 to 8 months I was able to graduate to a walker.  To this very day I must still use the walker if I am going to be walking a lot.  (It has a seat, so I sit down when my legs hurt or get tired.)

Ever since June 23rd 2010 (I believe is the exact date) I have been off gleevec.  My oncologist wanted to give me some time (since I was dealing with my horrible leg problems) before starting me on tasigna.  After about 2 months he wanted me to start tasigna.  I said NOPE!!!  I told him the only way I will start tasigna is when the leukemia shows up in my blood again.  He respected my wishes.  He said it could come back right away or it could be years.  So far it has been 1yr and 3 months.  I pray to God asking for a miracle that the gleevec cured me.  From what I understand there is no evidence that gleevec cures but I do know that with God anything is possible.  =D

Take care all of you!!  God is in control!!

Penny

Message was edited by: pennyarizona

[Trey]

A year ago your PCR was very low (.002%).  Assuming your PCR numbers are still low, the Gleevec break sounds like a reasonable idea.  It could help your body adjust better.  And re-starting at 300mg and working up to 400mg is also an acceptable option.  So it seems like a good plan.  Others can relate their actual experiences with a Gleevec break.

[pennyarizona]

Trey thanks for your response.  Have you heard of someone just staying on the 300mg and it still working?

[Trey]

There are some who take 300mg on an ongoing basis due to low counts and do just fine. But they usually need to have a fairly low PCR to do that.  If someone is trying to reduce a large leukemic burden, then 300mg is not high enough for most people.

[scuba]

Trey - You mentioned "reduce a large Leukemic burden" ... Question:  If the higher dose is needed to get at the leukemia cell population, then when people become PCRU - why doesn't the protocol call for dropping dosage significantly for maintenance purposes?  Once the cells are largely gone, seems like there is a lot of Gleevec chemical circulating with no where to go (and perhaps cause toxic affects elsewhere) ?  All you want is some Gleevec around that attaches to an undetectable level of cells as they emerge from the originating stem cells.

[simone4]

Penny, I have been on 300mg. for over a year. I was dx in Jan.09 and within

4 months it had to be reduced due to persistant itching all over my body.

I had PCR at 6 months with over 2 log reduction. It did help with the side

effects and my PCR in March 2010 showed a reduction as well. This summer, however,

I have had joint pain in hips and knees.  Some is due to arthritis, according to

an Orthopod, but the rest is just Gleevec.  I came off the G. for one day to

see if the joint pain would go away and there was absolutly no pain. I could

not walk in May due to what I thought was a knee injury ( I entered into a

basketball game with my neighbor's kids and thought that was it, although

I felt no pain at the time).  That was a bad month and I could barely go up steps

or walk at all.  Ice, ibuprovin, nothing helped.  Finally, it got better but there

is still stiffness in the joints.  I was an athlete in France (my former home) and I know pain.

This is different. Like you, I can't figure it out. Has your pain not gone away in the

last two weeks? It seems that it should.

Sorry for being so verbose.  I just had coffee.

Simone

Message was edited by: simone4

[Trey]

Michael,

There is little interest in researching the lower dosage issue as maintenance after PCRU.  I personally believe it would be a good idea but have no data to back it up.  There is no motivation for drug companies, and researchers do not care that much about side effects unless they are debilitating.  Some Japanese studies showed patients reaching PCRU on 200mg steady dosage.  But 400mg has been shown to be an effective overall dosage, and Oncs will not violate recommended dosage instructions without a very good reason, such as persistant low counts.

[MACELPatient]

I have asked my Onc about reducing the dosage and they feel that with a lower dose there is a greater potential for resistance to emerge with the drug.  As long as you are tolerating the higher dose they feel as though you should stay the course.

[scuba]

It's about population control.  Gleevec is designed to attach to the ATP site that fuels the runaway cells.  So as long as Gleevec is in the blood, the Leukemic cells get attacked, and the Gleevec molecule is "used" up.  But when there are no more Leukemic cells around (below detection) - then the Gleevec molecule has to be taken out elsewhere (liver, other biofunctions) - could be more toxic as a result.  Makes me wonder why most CML patients complain of side affects developing months after starting Gleevec and not right away; there is more Gleevec in the blood than there otherwise would be.  The reverse is also true - increase dosage to quicken response.

It doesn't make sense to keep the same dosage after PCRU from a "population" model point of view.  But there may be another reason.

Of course, if I became PCRU - I wonder if I would cut my dosage (in half) to test this theory.  Probably not.  This discussion is more academic than practical.

[SunNsand]

   I was diagnosed 3/09 and started on 400 mg. then about June 09 I went down to 300 mg. I have been on 300 mg. ever since. It did help my side effects drastically but, as of last week, both my b2a2 and b3a2 are still detectible. I am starting to get uncomfortable with the 300 mg. When I see my Onc next time, I am going to ask if I can try 400 again. I have asked him about low dosage possibly causing resistance to Gleevec and his reply was the proof is in the pudding. Yes I keep trending down but I would like better results and I am not pudding

sunNsand

[pennyarizona]

SunNsand,

LOL  I am sorry but your post made me laugh.  I needed that.  I am not laughing at you of course I'm laughing at your onc.  I can't believe he actually said, "The proof is in the pudding."  That is hilarious!!

So being serious now...  So your counts are still going down on the 300mg but just not as fast as you would like them to go down?  Is that why you want to try doing the 400mg again?  I started taking 400mg July 23, 2009 and not long after that my onc told me that my tests show no evidence of the leukemia in my blood anymore.  So I am wondering like alot of the other people on here if going down to the 300mg would be good for me just as maintaining (and I am also hoping it helps me with my muscle side effect problem).

Thanks for your response,

Penny

[pennyarizona]

Hi Simone,

I am glad to hear that you did better and still doing well on the 300mg.  I have been of my gleevec 400mg since Wed. June 23rd and yes my legs have gotten better.  It is still bothering me when I walk far distances so it's not completely better.  I did try going to the movies the other day and that about killed me.  I do hope being off for one more week helps my legs go back to normal and then I am going to ask my onc if he is okay with me switching to 300mg.

Does your onc ever talk to you about going back to the 400mg just to see if you would have the same itching problem again?

Take care,

Penny

[SunNsand]

I guess I am just wanting to have undetectable bad boys. My Onc says I am "close" to a 2 log reduction. I have read that reaching PCRU within two yrs. gives you better long term results so I'm hung up on wanting PCRU within the next 7 mths. Once I've reached undetectible, I would probably try to come down to 300 mg again.

My Onc has said quite a few funny things to me, sometimes I laugh, sometimes I don't ... lol

SunNsand

[hannibellemo]

Michael,

Dr. Druker discusses in the website below when he would considering lowering Gleevec dosages.

Pat

http://leukaemiachar...where-i-fit-in/

[simone4]

Penny, I cancelled my movie date because I knew my legs would hurt and

sitting for that long would kill my knees. What movie did you see, by the way?

Also my counts have been low forever, so that is primarily the reason the onc

reduced my dosage. The itching was so bad I believe there was a covert threat

(coming from me, not him) that I would quit the Gleevec if he didn't do something.

He has never mentioned my going back to 400mg. He went over my counts

with me again last Monday and said I was in a good place.  He is a very good

"match" for me as a doctor.  He is always optimistic, engaging, and we share

alot of common interests.  Sometimes our visit involves our travels, jazz or

just assisting me with the one word I need to finish the Times Sunday crossword

puzzle,  He brings a freshness to each visit. I am very lucky to have such an oncologist.

Take care and have a nice holiday.

Simone

[pennyarizona]

Hi Simone,

I am so glad that you have a oncologist that matches your personality.  I have been seriously been thinking of switching mine.  He is so impersonal, he showed more emotion to my 9yr old daughter then he ever showed to me "his patient".  So I am very happy for you!  Don't laugh at me but the movie I went to see was Twilight Saga: Eclipse.    I am a huge Twilight fan, so much so that I am even reading the books and believe me when I say this "I am not a reader."  LOL  But it was a big bummer how I was so uncomfortable during the show with sitting so long and going up and down the stairs.  I really do hope my legs get better.  One things for sure I will never take walking for granted ever again.  I hope you have a nice holiday weekend also.

Take care,

Penny

[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.  [See later posting below for the exact quote and reference].  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.  Just a month 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 almost 100% of drug resistance occurs within the first 3 years 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 3 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.

So it seems that the issue of resistance vs intolerable side effects might allow Oncs the flexibility to use lower then 400mg dosages in patients where it makes sense, without undue fear of drug resistance.  If a person can stay on 300mg long term, why switch them to 400mg and make them take Neupogen and drug breaks constantly, and cause them to suffer with side effects?

Message was edited by: Trey

[bubbastanley1@gmail.com]

Hello Penny.

I live in Arizona too - Mesa  to be exact.
I was diagnosed in May of 2002 and on 400 mg. Gleevec for 5 years,  I had every imaginable side effect and finally thought I would have to  quit work because of  it. I had extreme blistery rash up and down my legs, very bad case of joint effusion ( very painful) and other things.   I consulted with Druker and asked him what we should do.  Druker suggested a break with  constant and thorough testing for blood work.  I took a 10 week break, and then resumed at 300 mg. for two years.  The entire time I was under strict doctor's care which I would not do without.  My point, I  never once even showed a mild increase but maintained my PCRU the entire time.It did take two weeks before any let up of the side effects though.  With resuming the 300 mg, the side effects resumed as well.   I have been on tasigna now for over 2 years, and I am really happy with it.  I  personally would not be afraid of taking a break.  I also would make sure you keep a tight look on your bloodwork and stay in touch with your doctor throughout it.

Best of luck and  hope you do well.

Barb 

[rct]

Trey wrote:

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.

Was just in his office in May, he and our current oncs do not feel that 200 daily is therapeutic.  Both him and our oncs also agree that nobody knows just how much is and isn't therapeutic, and certainly not a standard, since everybody is different.  Both also agree that the movment is on to the next drug, and that figuring this stuff out is not a priority.

Both teams also would like a plasma return of 1000.  In fact, at a plasma of 800 neither him nor them was happy with the 300 Gleevec, it wasn't quite enough.

Trey wrote:

But most docs revert to what they have seen drugs do in the past, so they are cautious about this issue until proven otherwise.

Yes, all doctors do what they did yesterday.  Most people do.  It is why it is so hard to effect change.

Trey wrote:

So it seems that the issue of resistance vs intolerable side effects might allow Oncs the flexibility to use lower then 400mg dosages in patients where it makes sense, without undue fear of drug resistance.  If a person can stay on 300mg long term, why switch them to 400mg and make them take Neupogen and drug breaks constantly, and cause them to suffer with side effects?

Because at the same time we would like to think this could and would be the way, we also have a very irritating ability to encourage such things as "crushing the cml", "beating down the bad guys", "smashing cml into undetectable ranges", and on an on and on.

It isn't a sports game.  It isn't Clash Of The Network Superstars.  It is cancer.  If reasonably low levels of disease are what will keep a person alive for a long time with a reasonable life, we need to stop parroting ridiculous metaphors that only lead to people thinking something is wrong because they don't have the lowest PCR in this hemisphere.  All you have to do is ask and most of these guys will tell you that they will take consistent reasonably low PCRs for a very long time over anything else.

In our case the PCRs have remained reasonably low even through 200 Gleevec daily for quite some time.  Unfortunately, her counts are still unhappily low after a week of Tasigna.  So off of it for another week, hope they get...maybe even near 1000 anc, and back on Tasigna at 400/day instead of 600.

And they don't seem at all worried about stopping for a while, and neither did Druker.  Defining "a while" is probably the real trick.

rct

[Trey]

RCT,

I agree with you that I was not clear enough about Dr Druker's postion on lowering dosages, so let me provide the actual quote from Dr Druker and the reference:

Quoting Dr Druker from the reference below:

"Certainly, I would consider lowering the dose for patients who have  had a least a 3-log reduction, have a very low risk of relapse, and  maintain this for a couple of years.  I would also consider lowering the dose for people with a complete  cytogenetic response who have maintained that for at least 4 years, when  I know their risk of relapse is extremely low, and for anyone for whom  imatinib is affecting the quality of their life.  How would I do this?  First of all, I'd look to see what doses did it take to get them to  their response. If they needed 800 mg to get to a complete cytogenetic  response, I'm not going to be eager to lower their dose. If we started them on 800mg, and they got a very rapid response, I  might actually think about lowering them. I would absolutely recommend  monitoring plasma levels and not reducing below a drug level of 500 ng/mL"

http://www.leukemia-lymphoma.org/graphics/National/LLS0803Transcriptfinal.pdf

To further clarify, my posting is addressing the original poster's question about "safety", although "therapeutic levels" got mixed in along the way.  Dr Druker obviously believes that 500ng/ml is "safe", and some can achieve that on lower levels than others.  But if you were confused I am quite sure there were others, so thank you.