12 replies to this topic

[jenz]

Hi everyone.  I just got back from Chicago where my 9 month bone marrow biopsy and aspiration were performed.  This is after 6 months of Gleevec and then 3 months of Tasigna.  I must say the first 6 months on Gleevec was a dream compared too that of 3 months on Tasigna.  I have experienced so many side effects on Tasigna from mild to severe.  So I finally decided at my appointment this week to bring up the idea of lowering my dose from 800 MG a day to 600 MG a day of Tasigna.  It would not be a temporary dose change but I see it as if I continue to respond to Tasigna at the new dose than I would forever remain on it.  My oncologist was very much opposed to this idea for a few reasons 1.) it goes against the suggested Tasigna dosing guidelines and 2.) if I lower the dose my risk of become resistant to Tasigna is higher.  My oncologist has only had patients who lowered their dose temporarily and then worked themselves back up to their original dose.

In the beginning I was on 400 MG of Gleevec and at 6 months I was 50% Philly positive so the recommendation was to switch to Tasigna.  I started at 97% and got down to 50% with Gleevec, never really becoming resistant to it just became suboptimal in the words of Dr. Mauro.  If I would have just started on Tasigna back in Novemeber I would have started on 600 MG rather than the 800 MG when you switch to it from another TKI.

My side effects lately have effected my QOL enough that I have really contimplated lowering my dose.  I know it is a risk and am very aware of what may happen.  My oncolgoist is proposing I switch to Sprycel before trying to lower dose of Tasigna.  But my thought it why mess up a good thing, I had a 1 log reduction on Tasigna at 6 weeks so why not just test lowering the drug and see how I respond. I find it more risky at this point to switch to a completely different drug.  What if I do not respond? and why give up on Tasigna so quickly? She did say I would need to be monitored more closely with a change such as this.

Does anyone know anything about the clinical trials as to why switched drug patients start out at 800 MG rather than 600 MG.  Or of studies that show the difference the 200 MG can make?

Has anyone else dropped from 800 MG to 600 MG and stayed at that dose permantly? How have you done?  Was it due to side effects or counts?  My request comes strictly from side effect issues as my CBC/CMP has all been normal pretty much since day 1 of Tasigna.  Sorry this is such a long winded post I just want to know other peoples thoughts.  I know ultimately my oncologist will fill my request even though she advises not too it is up to me.

[Trey]

It is technically accurate that the Tasigna dosing instructions from Novartis suggest 2 x 300mg daily for newly diagnosed patients, and 2 x 400mg daily for those who are "resistant or intolerant" to Gleevec.  It makes no sense to me to lump the "intolerant" in with the "resistant", but that is another matter.  In reality, you were neither resistant nor intolerant, you just wanted a faster result.  So your dosage could be 2 x 300mg anyway under the guidelines.  I have also noted that women will generally have greater issues with higher dosages of the TKI drugs, although that is not universally true.

A recent large study  showed that 300mg of Tasigna taken twice per day produces Major Molecular Response (3 log reduction)  at a rate twice that of Gleevec 400mg.  So if only 600mg Tasigna is twice as effective as Gleevec, why take 800mg, which  seems a very large dosage for most people.

http://www.cancernet...e/10165/1636076

If it were me, I would try to tough it out until the test results come back.  After that, I would lower the dosage to 2 x 300mg if doing well.  If not doing so well, I would either try Sprycel or stay on the high dose Tasigna if possible.  My last choice would be to stay on the high dose Tasigna.  It's just not worth it when Sprycel is available, and might treat you better.

I view these TKI drugs as expendable.  They are not my good buddy.  They are a tool, like a hammer or a Binford 9000 Bovine Husbandry Machine.  Either perform or I'll find another that will.  We are the boss, not the TKI, and not even the Onc.  TKIs and enjoying life should be compatible.

[susanlathers]

I heard recommended starting dose on Tasigna was 600 mg.  I started on 800 because after 5 yrs I had not achieved a neg PCR and  had severe plueral effusions on Sprycel.  After being on Tasigna for 3 month I was negative and when I remained neg for 1 year  I asked onc to lower it to 600.  She said ok. Then I asked again at next 3 mo apt to lower it to 400 and she said no.  I will continue to ask so long as I stay neg until I can get to the lowest dose possible.   I must admit I miss a lot of doses and am thinking maybe it might be better,  If PCR is still neg,  to stay on 600 mg.  I would rather be able to miss doses and not worry than strictly adhere to the 2 doses at 400 mg. I hope all this made sense.  Tasinga has been good for me, the worst side effect has been high blood sugar bad insomnia.  What I hate the most are the 2 doses and all the food restriction.  Small price to pay considering, I shouldn't even complain.

I've heard a lot of people who have had success with really small doses of Sprycel.

Susan

[jenz]

Well after receiving my results from my 3 month Tasigna bmbx.  My doctor is more willing to discuss dropping my dose.  My plan was to give the 800 MG dose another 5 weeks to see if the rest of my side  subside.  But now I am curious if the timing of dropping the dose matters.  My oncologist says she would go sooner than later so my side effects subside more, and I also do not get attached to thinking my results are tied to the 800 MG a day.  We would do another bmbx in 3 months from dropping the dose.  Also my oncologist said if we find that in 3 months we don't continue to see improvement I could go back to the 800 MG dose.  What do you guys thinking about the timing of dropping the dose? Is 800 MG for longer better? or is switching immediately better?

[Trey]

I would reduce the dosage now.  The stats show that 600mg and 800mg Tasigna have equivalent response rates, and you are doing very well.

[jenz]

Thanks everyone for responding to my questions.  I am about 99% sure I will lower my dose.  I am just waiting on Dr. Mauro's thoughts on the matter then I will pull the trigger on it. 

My cousin who is a great researcher found this study out of MD Anderson which I thought held some merrit so I thought I would share.

http://www.ncbi.nlm....dose" nilotinib

[scuba]

For what it is worth - I had a significant dose reduction while on Sprycel along with outright dose interuptions for most of this year.  I started out at 70mg Sprycell (notice not the full 100mg. as usually prescribed) and was reduced to 20mg. Sprycel after just two weeks due to severe myelosuppression (ANC < 0.1).  After 4 months of zero TKI and slow blood recovery,  I was put back on 20mg. Sprycel when my ANC finally made it above 1.0 and have managed to stay at 20mg. Sprycel for 3 months now.  Two months into the re-start, I had a PCR test and saw my  PCR drop 2-log from 55% to 0.5%. (intl. scale) and FISH is at zero.  And my one month CBC just taken a few days ago showed that my blood is continuing to improve (albeit slowly) so it seems myelosuppression is under control.

Dr. Cortes at M.D. Anderson ordered the dose reduction/interuption plan without stim shots.  After my response, he has ordered a full review of my case in early November (bone marrow included) to track the progress.  He has told me that my response was deeper than he expected on 20mg. but not out of bounds.  I asked if I can increase my dose to 50mg. or even back to 70mg. believing more is better - but he said no.  He wants to find the right dose per patient that is effective.  More is not better.  More is just more.  Why put up with worse side affects when you don't have to in order to achieve results.

Dose reduction is definitely a reasonable course of action for your case as it was in mine.  M.D. Anderson is doing a lot of research on dose, specifically to address problems in this area.

(Full disclosure:  I do take 1600 mg of BCM-95 Curcumin every day along with the Sprycel.  Part of the review at M.D. Anderson is to track this more closely.  It is possible the Curcumin is aiding the Sprycel effectiveness at the low dose as was reported in colon cancer studies.  We just don't know in CML and I am not willing to stop taking Curcumin to find out.  There are others who have taken Curcumin with Sprycel for CML with no added benefit although I don't know what dose of Curcumin (effectiveness is very much dose dependent) was taken.  Ultimately full scientific trials would have to be conducted with suitable controls to determine if adding secondary treatments alongside a TKI has merit.  I am also part of a 'quality of life' study at M.D. Anderson to track side affects related to dose.  At 20mg. I have no side affects that I can feel.)

[jenz]

Michael thank you so much for your response.  That study I posted a few hours ago involved Dr. Cortes.  I have heard great things about him.  I was curious if you have his email address? or maybe his nurses? I would love to get in contact with him for a few questions I have on this topic.  You can send me a private message via the boards or email me at jenzcml@gmail.com if you feel comfortable providing it.

[jenz]

Well I've been on the lower dose of Tasigna for one week now and I must say I haven't felt all that better. If anything my fatigue/bone pain which had went from being constant to infrequent is back to being constant again. I had been asking myself all week am I adjusting again to the new dose? I just don't get that though why would my body have to adjust to an existing medication that you just lowered.  So I hope these aren't signs that I required the higher dose.  I was really hoping I would notice some kind of difference between the 800-600 MG doses.  Has anyone else noticed this?

I got to get my montly blood work next week which might be the tell all or not.  Then in another 5 weeks I will get a PCR done to get a sneak peek of how I am doing on the lower dose.  So until that time I do not think we will fully know anything. 

[gbarrett]

Hi Jenz,

I am also on Tasigna since August (diagnosed with CML in July) and I started at 600mg per day. I am 5'6" and 110 lbs. and the migraines were unbearable so my doctor stopeed it for a week then restarted me at 300mg per day (150mg in the am and 150mg in the pm) and since then I have reached hematological remission. My latest blood test, FISH, has show to be negative however, the next BMBx in is in February and the doctor will not lable me with the second stage of remission until then. My dose seems to be working very well for my size and side effects are all but nil. I should mention I was diagnosed in chronic phase. Does anyone know why Tasigna is not administered as other drugs are where it dependes on your body size and weight?

[Trey]

The drug manufacturers do not believe there is sufficient data showing a relationship between body size and dosage.  But anecdotal info as I see it appears to show that women have more issues with low blood counts than men. 

[GerryL]

Hi Trey,

Quick question if Jenz could get her results from Tasigna down to PCRU would it be possible to switch back to Gleevec and use Gleevec to maintain the PCRU, if Gleevec give less side effect issues to Tasigna?

[Trey]

Probably.