34 replies to this topic

[lala]

Trey,  You still take Gleevec, right?  Have you lowered your dosage?  The lower dose doesn't scare you?  How long ago were you diagnosed?  I am considering it.......3/2006 was my diagnosis.....HAVE OTHERS ON THIS BOARD GONE DOWN TO 300?  At my appt this week, my doc said he doesn't like 300.....would love to hear the pros and cons from this board of patients!!  THANKS, Lala

[simone4]

Lala, I am on 300mg. and MMR.  I had to go to 300mg.because of low

counts and horrible side affects (itching 24 hours a day.) My hem/onc has

no problem with reducing G. and has consulted several of the CML

gurus and they seem to agree. I have had confidence in him since our

first handshake in 1/09.  I am closely monitored, every 6 weeks for

BW and every 6 months for PCR.  I have had yearly BMB's.

All is well for now. A lot depends on the doctor you have. In this

respect I am very fortunate to have such a good partner in my

treatment.

Good luck.

Simone

[Trey]

OK, only because you asked me.....  I am taking 200mg Gleevec per day, and have been for close to 3 years now.  I started on 400mg Gleevec and reached PCRU in just over 6 months.  I continued to take 400mg Gleevec for another couple years, then went to 300mg for a few months, then finally to 200mg, which has been my dosage for nearly 3 years.

I had not advertised this previously because I did not want to encourage anyone else.  But it has worked well for me for several years now, including reducing side effects.  I would not have done this if not PCRU for over 2 years.

I think RCT would say at this point: "Your mileage may vary".

http://community.lls.org/people/rct

[Susan61]

Hi Trey:  I am so glad that you shared that information.  That is fantastic.  I am still on my 400mg. a day, and not sure if you saw my post 2 weeks ago.

My Oncologist told me that within 5 years there will be a test to see if you would get your CML back if you have been PCRU for so many years if youwere to stop your TKI..   I am PCRU now for 8 years, and some people think I am crazy to still be taking my Gleevec.  My Oncologist said that you would be considered cured according to this test whatever it is.  You know I have had CML for 13 years this Dec., and I was always told that there is no cure without a BMT. Was it your choice to reduce the dose to see what would happen, or was it your doctors recommendation?

Its a lot for me to absorb.  I just feel that if I am doing good, why mess with a good thing.  I guess time will tell as to what I will do

I am learning something new everyday, but I  still get lost when everyone talks numbers and specifics.  We all depend on you so much.

Susan

[lala]

Ooooooohhhhhhhh......how interesting!  How old were you at diagnosis...or is that asking too much?????  Maybe you want to be mysterious about it!  I am soon to be 55.....YIKES!  Sounds like we had the same luck with G.  I was pcru real fast too.  I have hit the 5 plus year mark.........tired of only having a couple hours of energy in me each day.....HOW DID YOU DECIDE TO TRY 300 then 200?  Thanks for your honesty!  APPRECIATE IT!  Lala

[lala]

Hi, Susan,  just want to tell you that I appreciate your kindness to all!  You always welcome everyone and have kind words .....hope you're having a good day!  Lala

[lala]

Whose idea to do 200?

[Susan61]

Thanks Lala:  I guess I just treat people the way I want to be treated.  My heart goes out to anyone that is new, and they have no idea what they are facing.

None of us ever forgets how we felt at our initial diagnosis, and I like to try to calm people down to let them know it gets better.

Glad to see you are PCRU also.  Gleevec has been good to a lot of us.  Another thing I always tell people that is if you just started Gleevec, and your getting a lot of side effects don't try to jump off of it onto another one hoping it will be better.  If its working for you, try to endure the side effects for awhile because they do get better in most cases.  If not, then by all means talk to your doctor about the possibility of one of the other drugs.  My concern would be that would another drug work as good.  We are all different, and the same drug does not work for everyone.

Yes, there is a lot of good things going on with the treatment of CML for a future to look forward to.

Susan

[Trey]

I decided on the dosage reduction, and chose the timing and dosages based on studies showing that some patients who are very responsive to Gleevec have achieved PCRU on 200mg per day.  The theory is that a "speedy responder" should need less drug than a slow responder.

And I do not personally believe in the "low dosage resistance" theory, which makes no sense to me.  A few years ago the leading Oncs were  expressing concern about dosages below 400mg causing drug resistance.   These same Oncs have softened their statements over time.  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.  Quoting Dr Druker:

"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-...scriptfinal.pdf

So Dr Druker obviously believes that 500ng/ml is "safe".  And some can achieve that on lower levels than others -- some maybe on 300mg, and some on 200mg per day.  This is where "your mileage may vary".  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.  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 resistance occurs within the first year or two after diagnosis as the low  level resisting cells grow slowly over time to detectable levels while the non-resistant cells are killed off.  That is why the leading Oncs say that if we make it through 2 - 3 years without  drug resistance, then it will not likely occur after that (but there can be rare exceptions).  [NOTE: I am NOT implying that Dr Druker or Dr Shah would agree with my actual dosage reduction.]

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 antibiotic dosage), then that bacteria may just be "stunned" but then 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 older 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 this  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 (any of them).  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 TKI resistance (which has always been unproven) should not be an over-riding concern in the face of bearing long term side effects.  This should allow Oncs the flexibility to use lower dosages of Gleevec, Sprycel, or Tasigna in patients  where it makes sense.

Another issue is relates to leukemic burden.  At diagnosis most of our WBCs are leukemic and there are about 20 - 30 times more than average.  At PCRU very, very few are leukemic and the total number of WBC cells is normal or often less than normal.  So why would it take the same drug dosage to deal with these various levels?

If a person is PCRU for over two years and can decrease to 300mg or even 200mg Gleevec for the long term (or simliar reductions in Sprycel or Tasigna) why make the patient continue to take full dosage forever and suffer with side effects?

[ChrisC]

IMHO, excellent thinking, beautifully expressed. Thanks, Trey.

[GerryL]

Hi Trey,

I still have to get to PCRU and then maintain it for two years - hopefully by then there will be more information out on reduced dosages and my doc will have changed his mind. At the moment he is strongly against eventually reducing my dosage and would rather switch drugs if my side effects were too bad.

[valiantchong]

Hi Susan,

You are saying that you onco said there will be a test in five years' time able to test if one will progress or could stop medication, wondering if you could be more specific on the name of the test or the method of test ? Pls share if you could, wish it could come sooner....

Thanks for sharing

[scuba]

Trey - fascinating conversation.  I didn't believe you had it in you.  To experiment that is - and not give into fear.  Let the snake out, etc.

I suspect that if your PCRu status changed (i.e. you became detectable), you would increase the dose back up or even change drugs?

It's good that you lowered your dose so that your quality of life has gone up.

The dose issue is a rate control problem.  Depending on how aggressive the CML is for each of us determines the amount of drug needed to get the slope right (a downward slope).  It's not just "resistance".  It's population dynamics.  If the drug dose - whatever it is - causes a significant drop to occur - then continued taking of the drug at that dose will continue to reduce the load in a steady way (more or less, not quite linear) downward to PCRu.  Some patients never get to PCRu, but maintain near it in MMR, for example, but it is not a dose related issue at that point.  It doesn't matter how much drug is in the system, there is a balance that has been achieved.  The key is to get the slope right and then maintain that direction until it levels off.  Some level off at low levels - some, like you, keep going until undetectable.  In my case, the 20mg Dasatinib - 5 times lower dose than normally prescribed is having a big effect now.  The key was to be able to stay on it steadily.  But since this dose is working - it will take me down to whatever stable level is normal for me - hopefully PCRu - but if it didn't take me to PCRu - no increase in drug would be effective.   It works this way very much for the reasons you discussed.  The drug hits the pocket and dead goes the cell.  Resistant cells may be there and they increase in relative proportion - that is, in fact, where the problem is as you described.  Many of us have initial great response - we certainly get the symptoms eliminated (i.e. high WBC's, etc.) - but over time one population gets replaced with another and we need a new drub.  But if that doesn't happen - as with you - all it takes is sufficient drug, more than division rate, and the population crashes downward.  I'm sure there are other factors, but that's basically it.

In your case and Susan's - you achieved PCRu quickly and maintained it for years.  There are very few, if any, leukemic cells left.  A small residual dose of a TKI is all that is probably needed - or some other agent that can mop up the stray cell, but as long as the division rate is less than the level of TKI needed to keep the slope right.

I actually believe you and Susan are cured.  There's nothing left.  Any new CML would be a new origination of the disease.  In which case you are both already onto it because you have regular PCR tests.  You would discover it quickly at low level and can jump on it.

Thank God for the TKI's - they let us live with a genetic disease.  Thank God also you don't have to keep taking it.  You can go on and off as required.  I'm living proof of that.

Trey - thanks for informing us of your gutsy move.  In my mind - it was no risk at all.

[Skittles]

Wow Trey!  Thanks for such a thorough explanation of the why a lower dose of TKI might be a possible choice for some of us as time goes along.  I am very encouraged by this information and thank you so much for all of your research and willing to share.  I am glad lala asked you about this!!  From your post it looks as though you might have first posted this on March 27, 2009.  Thanks for re-posting for those of us not already on the group at that time. Have a great day!  Skittles

[nathaliece]

Trey --

Thanks for sharing and educating us ... again!  I was just diagnosed in 11/10 and hope to achieve PCRU by the end of the year.  It is nice to know there is a possibility of a lower dosage in the future.  The time you take to share and offer explanations to us is really appreciated.

Nat

[Tom_md]

Hello,

i thought I would throw im my 2 cebnts worth.

I was diagnosed 3 years ago this month.  I wasa 44 years old at Diagnosis.   I have certainly have had some tough struggles at time with side effects.  I'm sure many can relate to this.   I responded very quickly to Gleevec at 400 mgs.  I was PCR-U in about a year.  My side effects seem to come in cycles, where I feel pretty good all the way to I can barely do anything due to fatigue but also have a lot of muscle joint issues.  This past February my Onc reduced my dosage to 300 mgs.  I had a PCR done May which was still PCR-U, then I just had another draw the other day.  Next Wednesday I should get the results.  I still struggle some with side effects, fatigue has been greatly reduced until very recently.  ( I do stay pretty busy, work full time and have two young children).  Sometimes I think I need to just give in and rest and it improves.  (take it easy for a f ew days)  Interestingly my joint pains seem to have gotten worse pretty much stayed steady or gotten worse the whole time.  ( I may be experiencing the effects of aging and arthritus and may nnot even be Gleevec related)  Digestive issues dramatically reduced, and I feel like fatigue will get better as soon as I can find some time to cool it a little.  As a whole the past 6 months have shown a marked improvement, my wife has commented that I generally look better etc.

I would consider dropping to 200 mgs within a year or so as long as I stay PCR-U>  It is encouraging to me that others may be having success witht his as well.

Take care everybody,

Tom

[lala]

Wow....I am sooo hopeful!!!  Thank you to everyone who responded to this.  I think I will go down to 300!  Just in time to start school!  YAHOO!  Wow....just to get a little of my old life back would be awesome!  Just this week, the doc said no, but I barely mentioned it to him.....I did not have this info to present to him!  .  Simone, how do you take your 300?  Happy to hear your info regarding the gurus being ok with this.  Trey, how do you recommend taking the pills...I do have the 100's so that makes it easy!  Tom, how do you take yours?  Trey, do your docs know you are on 200?  Do I need additional BW after the switch?  THANK YOU TO ALL!  I HAVE A NEW SKIP IN MY STEP!  Don't I sound old....ha!  Lala

[Tom_md]

I take 3 tabs (100 mgs) at dinner/close to bed time.  I have always gone for labs every three months (at least once it was apparent the G was working well)

Keeping my fingers crossed for Wednesday, I'll post how it goes.

Tom

[simone4]

Lala, I take 3 (100 mg. of Gleevec )at night. I usually take it

with yogurt, banana or something light. It has helped reduce

some of my side effects, but fatigue remains a problem.

[lala]

Nnnnnoooooo...I want no more fatigue!!!!!!!!!  . Would it help to take the pills throughout the day.....I know when I took my big 400 at bedtime, the deep fatigue in the morning just about killed me......taking smaller pills twice daily has helped this.......wonder if 3 100s can be spread out.....am I getting a little too carried away!?