25 replies to this topic

[scuba]

See link below:

 

TKI's (other than Gleevec for some reason) are linked to vascular events. A vascular event can be arterial thrombosis, occlusion or other negative artery events.

 

This is why it is so important to consider dose reduction and cessation whenever possible. Full dose may not be necessary or even "wise". And cessation is worthy of consideration for anyone who has been PCRU for more than one year (which is a drop from the previous two year consideration). For those patients there is a 50-50 chance that you can continue drug free with regular monitoring.

 

TKI's are serious drugs with damaging effects that are showing up as more patients take the drugs for longer periods of time.

 

http://www.cancernet...vascular-events

[tiredblood]

Just sitting here waiting, with slightly swollen ankles, for the hem/Onc to come in and tell me my latest PCR results after starting back on nilotinib at a reduced dose.

[scuba]

I am doing everything I can to terminate my taking a TKI. I am close ... I only take 20mg of Sprycel (from the 100mg normally prescribed) - so that helps. I will keep trying cessation. I won't wait the customary two (or even one) year. These drugs are life savers - but once saved - time to move on eh?  I stopped one year ago this month ... only to return nine months later when the tell tale signs of "relapse" started to appear. It was subtle; I could have gone longer as my own Oncologist suggested, but I decided to test that I can drop my PCR back to near "undetected". It worked (.. no real surprise since the data suggested that is exactly what would happen).

 

My next try at cessation will be in another nine or so months after holding PCRU (i.e. < 0.01%) and hold it for one year - then off Sprycel I go. 

 

Sooner or later the Leukemic stem cells have to burn out ... or they discover a way to enhance our immune system to do the job.

 

artery occlusions concern me more than going off then back on Sprycel.

[hannibellemo]

Scuba,

 

My onc brought this up at my appt. last week, especially concerning Sprycel. The least amount of drug you can take and still have a good response...

[DebDoodah22]

Why won't my onc take this approach? I cannot understand this.
I have been asking for dose reduction for awhile.
The onc wants PCRU for a couple of years first, but the rest of my health feels like it's declining.

I am not on full dose but have been on 80 mg Sprycel and have been foray least 18 mos.
To me the SE are still disturbing at this dose.
My weight and my BP (150/87) are going up.
My shortness of breath is getting worse and now interrupting my sleep.
PCP ordered Chest x-Ray but that does not show PE or new anomaly.
Latest blood work maintains MMR - .034, although there's a slight increase from previous .031.

My next big labs and onc appt are early March.
What could I present to him that would make the most logical or
persuasive case for dose reduction?

[scuba]

Why won't my onc take this approach? I cannot understand this.
I have been asking for dose reduction for awhile.
The onc wants PCRU for a couple of years first, but the rest of my health feels like it's declining.

I am not on full dose but have been on 80 mg Sprycel and have been foray least 18 mos.
To me the SE are still disturbing at this dose.
My weight and my BP (150/87) are going up.
My shortness of breath is getting worse and now interrupting my sleep.
PCP ordered Chest x-Ray but that does not show PE or new anomaly.
Latest blood work maintains MMR - .034, although there's a slight increase from previous .031.

My next big labs and onc appt are early March.
What could I present to him that would make the most logical or
persuasive case for dose reduction?

 

Hi Deb - 

 

There is no difference between your  0.034 current test and the previous 0.031 test - NONE. Forget the third decimal place. It's meaningless. At 0.03 you are doing very well. Almost a log below MMR. You can easily try dose reduction for one month and re-test.

You have a good chance at success.

 

Also - for weight gain and hypertension creeping up, it could very well be your Thyroid:

 

http://www.ncbi.nlm....pubmed/20929406

 

Sprycel affects the thyroid. Most complaints around here about fatigue, weight gain, etc. may very well be traced to underactive thyroid brought on by second generation TKI's. At M.D. Anderson, Thyroid tests are now routine because of this "discovery". Another reason to reduce dose and try cessation. You should have a free T3, free T4 and TSH hormone levels checked. TSH will be most informative. If it's high, your Thyroid is struggling.

 

Tell your oncologist that testing dose reduction incurs ZERO risk of progression for you. Studies show that even if your PCR climbs (and it would have to increase by a 1/2 - 1 log to be a significant increase), you can resume former dose and bring it right back down. 

 

Below is a nice summary of the different TKI's (including Sprycel) you can share with your doctor:

 

http://www.bloodjour...so-checked=true

 

Chance are he hasn't read it. They just stick to what they know which is often out of date. 

 

For what it is worth, I am on 20mg Sprycel and below 0.01 PCR. I am considering a one month on, one month off strategy or a one day on, one day off strategy to continue my quest to wean myself off Sprycel. 

[kat73]

But doesn't the Larson article cited above undercut the argument for dose reduction?  In the last paragraph under "Side Effects," he concludes,

 

"it may be possible to minimize toxicities by reducing the TKI dose in patients who have had deep molecular responses but this strategy remains to be validated." 

 

Meaning, not yet, folks, not on our watch out here in research land - we cannot recommend it. He doesn't even include patients who want to try reducing dose who are only at MMR level.  My experience is like DebDoodah's - my onc (who is a CML researcher) won't budge on dose reduction, even though I've been at or below MMR for 4 years.  Meanwhile, I feel strongly that side effects are increasingly impacting my QoL.  I won't go against him, because I respect his brains.  But, like DebDoodah, I am searching for some "ammo" for a good argument to persuade him to let me try.  Unfortunately, the Blood Journal article didn't give that.

[scuba]

But doesn't the Larson article cited above undercut the argument for dose reduction?  In the last paragraph under "Side Effects," he concludes,

 

"it may be possible to minimize toxicities by reducing the TKI dose in patients who have had deep molecular responses but this strategy remains to be validated." 

 

Meaning, not yet, folks, not on our watch out here in research land - we cannot recommend it. He doesn't even include patients who want to try reducing dose who are only at MMR level.  My experience is like DebDoodah's - my onc (who is a CML researcher) won't budge on dose reduction, even though I've been at or below MMR for 4 years.  Meanwhile, I feel strongly that side effects are increasingly impacting my QoL.  I won't go against him, because I respect his brains.  But, like DebDoodah, I am searching for some "ammo" for a good argument to persuade him to let me try.  Unfortunately, the Blood Journal article didn't give that.

 

I don't have the link handy to Dr. Cortes' video presentation he did recently at an LLS symposium, but in it he specifically cited dose reduction as a viable plan of action to manage side effects. This is especially true for patients who are MMR or below.

 

We do have real live examples - people like myself - on this forum who have reported experience with dose reduction, cessation and PCR response. I stopped Sprycel altogether for 9 months last year while barely PCRU and did experience an up and down movement in PCR with an overall rise of one log. I decided to resume and in two months PCR plummeted right back down. All with my Dr.'s knowledge and guidance. He did not approve this approach, by the way, but once I did it, he accommodated and was pleased with the results.

 

Few doctors are going to take professional "risk" and go outside the guidelines. And for good reason. We're a litigious society and want the experts to take responsibility if something doesn't go right. Fair enough. But there is a lot of data out there - "in research land" that supports dose reduction as a viable path to take to manage side effects AND maintain response.

 

One additional point, my doctor - who is a researcher in the field - put me on very low dose to manage side effects when I wasn't even CCyR. The custom at the time was to use stim shots to keep blood levels up while on full dose. He suggested low dose to start and see where we go as I had few blasts that would be of concern to him. I have been on low dose ever since (apart from cessation attempt) and managed to achieve CCyR quickly and then on to MMR and in/out of PCRU. I have no side effects that I can feel.

 

At the end of the day, you have to do what you feel comfortable doing and trusting the doctor you have faith in knows what he or she is doing. I'm confident there is an "article" out there you can use to help educate your doctor. One size - full dose - does not fit all. Our disease and the treatment deserve individualized treatment plan.

[mdszj]

In mid-December 2015 I decreased my S from 100 to 80 mg.  I definitely feel better.  I have been undetectable since Oct 2013, except for a blip above then going back to pcru over a year ago.  I will have my first blood draw since going to 80 next week, should be interesting.  Assuming I am still pcru I plan to tell my local hemo I want to put together a plan for slowly reducing dosage.  If he balks I am planning to cut the 80s in half and alternate 80 then 40 (half a pill) and see how that works out.  Then I will ask for forgiveness afterwards if he yells.

 

Does anyone have any thoughts on alternating dosages like this?

[Buzzm1]

In mid-December 2015 I decreased my S from 100 to 80 mg.  I definitely feel better.  I have been undetectable since Oct 2013, except for a blip above then going back to pcru over a year ago.  I will have my first blood draw since going to 80 next week, should be interesting.  Assuming I am still pcru I plan to tell my local hemo I want to put together a plan for slowly reducing dosage.  If he balks I am planning to cut the 80s in half and alternate 80 then 40 (half a pill) and see how that works out.  Then I will ask for forgiveness afterwards if he yells.

 

Does anyone have any thoughts on alternating dosages like this?

Sounds like a plan mdszj ... if you felt better after just a 20mg reduction, you are going to feel immensely better as you decrease your dosage ever further.  Best of Luck to you ... 

[scuba]

In mid-December 2015 I decreased my S from 100 to 80 mg.  I definitely feel better.  I have been undetectable since Oct 2013, except for a blip above then going back to pcru over a year ago.  I will have my first blood draw since going to 80 next week, should be interesting.  Assuming I am still pcru I plan to tell my local hemo I want to put together a plan for slowly reducing dosage.  If he balks I am planning to cut the 80s in half and alternate 80 then 40 (half a pill) and see how that works out.  Then I will ask for forgiveness afterwards if he yells.

 

Does anyone have any thoughts on alternating dosages like this?

 

I wouldn't cut the pill in half. They are coated and intended to be digested whole. You might just alternate every other day.

I am considering one month on / one month off myself. 

[kat73]

Scuba - I probably should have included that my onc already reduced my Sprycel to 70 mg soon after I came on board with him.  It was because I had made a nice sustained jump downward on a couple of PCR's, but continued to have myelosuppression.  The latter improved steadily over months and the PCR remained stable, so he was fine with that.  He just won't reduce any further just for puffy eyes and face, extreme fatigue and weakness, and cadaver-white skin (among other stuff.)  Just for my info, can Sprycel be cut in half successfully?

[scuba]

Scuba - I probably should have included that my onc already reduced my Sprycel to 70 mg soon after I came on board with him.  It was because I had made a nice sustained jump downward on a couple of PCR's, but continued to have myelosuppression.  The latter improved steadily over months and the PCR remained stable, so he was fine with that.  He just won't reduce any further just for puffy eyes and face, extreme fatigue and weakness, and cadaver-white skin (among other stuff.)  Just for my info, can Sprycel be cut in half successfully?

 

Have your Thyroid checked to rule out thyroid induced fatigue. Sprycel can induce hypothyroidism in patients.

Sprycel tablets should not be cut in half:

http://www.sprycel.com/taking#

 

The reason you should not cut them is that the medication is 'film-coated' to facilitate proper absorption - either to slow down dissolution in the stomach or delay dissolution until it moves into the small intestine. Cutting the tablet in any way exposes the drug to stomach fluids without the film-coating. Because the half-life of Sprycel in the blood is so fast (5 hours) - taking your current dose every other day would have the effect of taking 1/2 the dose every day. That would be better than cutting the tablet. 

 

Regarding lowering dose - I would suggest to your Oncologist that you would like to lower to 40mg and then test PCR at one month intervals for 2-3 months to check response. If response is unchanged, then that can be your new dose. 

 

Tell him you know patients who are taking only 20mg and are near PCRU and were prescribed this low dose both for myelosuppression at first and then continued therapy when it worked. Feel free to mention that this patient is treated by Dr. Cortes, a researcher in the field. Hopefully your Oncologist knows his work.

[kat73]

Thanks, Scuba, all very good advice.  Since I had my thyroid out in 1979 I've been on Synthroid or generic for a long time, and have had many, many, MANY thyroid checks!  They are routinely done for me now and have always been normal.  So, that ain't it, darn it.

 

I won't cut my Sprycel in half, and I will ask him the way you described.  It makes it seem eminently reasonable.  However, it won't be persuasive to him to tell of your experience or others on this forum, even if Dr. Cortes says it's OK (and yes, I think they're pals) because it's anecdotal and outside clinical trials.  Plus, I suspect he's already got a bead on me in his mind - I'm older, have the pesky co-morbidities, have always been a turtle - not your scenario at all - and it could very well be that he suspects I'm never going to be in that TFR group.  I think I had a good Sokal score, but it was never recorded, and I never had a BMB, so there's really no knowing if I would be OK rocking the boat.  He just doesn't want to let me sink and drown, when he had a lifejacket handy all the time.  I get it.  I just hope he'll agree (and the insurance company will agree) to just let me TRY it.

[mdszj]

Buzz and Scuba

 

That is good info regarding the cutting in half.  I am guessing that if you cut it, the surface of the fresh-cut, uncoated portion will dissolve faster when it is exposed to the stomach acid, since TKIs are much more soluble at lower pH.  In my desire to reach undetectable quickly I used to eat a lot of acidic foods when I took my pill such as salad with oil and vinegar, crystal hot sauce (also with vinegar), mustard/ketchup, etc to make the S more soluble and therefore absorb it more.  I thought I read somewhere that about 85% of sprycel goes thru the intestine - not sure if it eventually gets absorbed or is eliminated.  I just looked for the reference but can not locate it.  

[Calvink669]

Buzz and Scuba

 

That is good info regarding the cutting in half.  I am guessing that if you cut it, the surface of the fresh-cut, uncoated portion will dissolve faster when it is exposed to the stomach acid, since TKIs are much more soluble at lower pH.  In my desire to reach undetectable quickly I used to eat a lot of acidic foods when I took my pill such as salad with oil and vinegar, crystal hot sauce (also with vinegar), mustard/ketchup, etc to make the S more soluble and therefore absorb it more.  I thought I read somewhere that about 85% of sprycel goes thru the intestine - not sure if it eventually gets absorbed or is eliminated.  I just looked for the reference but can not locate it.  

I was actually instructed by Dr. Kantarjian at MD Anderson to cut my 100mg sprycel in half when he reduced it to 50mg as I had just ordered a new supply right before my visit.  He said that the drug industry tells you not to do that so that they make more more when dosing changes and that it absolutely makes no difference.  I thought this was kind of funny and actually expected since he really hates the prices charged for these drugs that save our life.

[tiredblood]

FWIW, I was on Tasigna for 22 months achieving a complete molecular response within 3 months of starting the TKI. Just as my hem/onc suggested (most people loose response within 6 months), I lost response within three months of cessation.  I have started it back and 1/2 the dose.

[Buzzm1]

when necessary to achieve the desired dose, I break my coated Gleevec pills in half; they are coated to help prevent leaving that shitty taste in your mouth, along with toxic material on your hand and fingers ... with dinner I take a 1,000mg Vitamin C to help generate additional acid, along with a Tumeric tablet, and then take my Gleevec dose anywhere from 30 mins to an hour after dinner.   For me it helped to eliminate that nauseous "I feel like throwing up" along with stomach problems, that I had all too often during those first months/first year, maybe two, on Gleevec 400mg).  

[TeddyB]

I wonder when/if my CML stemcells will get tired and die, i just cant seem to get rid of the last few cells. Forever on a plateau.

Seems like cessation is still a bit off for me, but maybe i could try dose reduction at some point. My body is really hating the gleevec (400mg) these days. In april this year it will be 4 years since the start of my treatment.

 

Month:    ABL1
1              76
2              17
3               3
6             0,1
9            0,02
12          0,03
15          0,04
18          0,01
21          0,01
24          0,01
27          0,03
30          0,01
33          0,03
36          0,01
39          0,01
42          0,01
45          0,01

[steelpony5555]

Hmmmm questioned my Oncologist bout reducing dosage when I get low enough,  but his thinking is if you are handling the med and not having any major side effects then why mess with success.  Says maybe way down the road we can think of it if levels are holding.  But he is thinking a long time.  I am thinking why would I risk a relapse if things are going along well.  Sorta like poking a sleeping bear, you could get bit.....