29 replies to this topic

[jmoorhou]

Trey, just wondering if you have remained undetectable after reducing your dose of TKI.

 

Thanks so  much.

[Trey]

Yes on 200mg Gleevec, except stopped entirely then lost PCRU.  Started low dose Sprycel 20mg and regained PCRU quickly.

[Gail's]

Good news, Trey. I'd like to drop from 50 mg sprycel to 20 mg before I try cessation. My onc reluctant since there's not much research 20 mg works. Can you direct me to any studies on use of 20 mg?

[scuba]

Good news, Trey. I'd like to drop from 50 mg sprycel to 20 mg before I try cessation. My onc reluctant since there's not much research 20 mg works. Can you direct me to any studies on use of 20 mg?

 

I am on 20mg Sprycel (see signature) and have been for years. I am listed as <0.01% M.D. Anderson scale. I don't have an absolute number because t am below the precision of the test. All they can tell me is that there is a detection, just not quantifiable.

 

20 mg works. Dr. Cortes prescribes it. He has many many patients at 20mg.

[jlegakis]

Trey, My HB has dropped from 55-60 to 35-40 after 9 mos. on 800 mg Tasigna. I feel fine and run 3-4 miles every other day. I've been a long distance runner for decades, but NEVER had a HB this LOW! I am at a CCyR for the last 6 mos. and was wondering IF my onc should lower the doseage to 600mg? A cardiologist had me do a treadmill test and said I dealt with the high intensity well, but I have an electrical STAGE 2 Heart Block that needs to be monitored with EKG'S periodically. He said I have a very strong heart muscle and was NOT very concerned. In fact, he noted that I have a so-called back-up system that acts like a pacemaker! Have you ever heard that Tasigna can play ~tricks~ with your H? It seems that I do NOT have any Qt-Prolongation issues, so what do you think?

[Gail's]

Hey scuba. Glad the 20 mg is working so well for you. Just looking for some actual research on that dose. Thanks.

[scuba]

Hey scuba. Glad the 20 mg is working so well for you. Just looking for some actual research on that dose. Thanks.

 

Here's some research for you:

 

https://www.ncbi.nlm...pubmed/28396095

Elderly Patients With Chronic Myeloid Leukemia Benefit From a Dasatinib Dose as Low as 20 mg. CONCLUSION:

Low-dose (eg, ≤ 20 mg) dasatinib therapy generates an adequate molecular response in most elderly patients with chronic phase CML without causing severe AEs.

[Gail's]

Thanks!

[cmljax]

Scuba:

Do you think the results would be the same for low dose Tasigna (equivalent would be about 150 mg) or is there something different about Sprycell that it works better at low dose than any of the other TKI's?

[scuba]

Scuba:

Do you think the results would be the same for low dose Tasigna (equivalent would be about 150 mg) or is there something different about Sprycell that it works better at low dose than any of the other TKI's?

 

In clinical trials there are several key phases that upon success lead to FDA approval. Two of these involve safety in which toxicity is assessed and that is dose dependent. And the second is pharmocokinetics (PK) / efficacy (does the drug do what it is designed to do).

 

During PK trials, researchers determine how much drug absorption occurs in the blood over time and how long it takes for the body to clear the drug (metabolite formation and elimination). What they have found in the case of Sprycel is that much of the drug metabolizes very quickly and clears the body. It is very potent at low dose. It's effectiveness does increase with higher dose, but not by much. In the case of Tasigna,, the drug does not clear the body as quickly (15 hours vs. 3-5 hours for Sprycel) and much of the drug (88%) remains un-metabolized. This is part of the reason Tasigna is taken in two smaller doses spread in time rather than just one bigger dose.

 

http://www.ema.europ...WC500034398.pdf

 

In my case with Sprycel, I was prescribed 20mg in order to avoid side effects (myelosuppression) as were many other patients. They discovered that 20mg was quite effective. This is not true for all patients, but is true for many. This is based on actual experience in the clinic. In the case of Tasigna, I am not aware of very low dose effectiveness, but during the FDA approval process they did note comparable effectiveness between 300mg twice daily and 400mg twice daily. (300 mg became the starting dose).

 

https://www.cancer.g...s/fda-nilotinib

 

As cessation attempts have proven to be mostly safe (i.e. no permanent loss of response), it is reasonable that a patient, in cooperation with their doctor), could try a low dose of nilotinib as you described with very low risk and "test" if it works. You would have to have monthly PCR's to verify no loss of response. Over enough time with no change - or even a continued down trend, one could then conclude that very low dose Tasigna is effective (for that one patient).

[cmljax]

Thanks for the response Scuba, but I am a bit confused about the metabolism numbers for Tasigna.  Does 88% un-metabolized mean that only 12% of the dose actually works on the CML versus a much higher % for Sprycell and therefore low dose tasigna would not be as effective in controlling CML as low dose Sprycell?  Or does it mean something else?

 

I am really seeking a best guess opinion as to which drug works best to control CML on low dose (say 20mg Srycell versus 150 mg Tasigna).  You may have already given that opinion, but would appreciate one further clarification - thanks

[scuba]

"I am really seeking a best guess opinion as to which drug works best to control CML on low dose (say 20mg Srycell versus 150 mg Tasigna).  You may have already given that opinion, but would appreciate one further clarification - thanks"

 

Data shows that Sprycel is taken up by cells more efficiently than Tasigna. But I have no data/insight/opinion on which drug works best to control CML at low dose. It is almost certainly patient specific. It would have to be tested. We do know that sprycel works quite well at low dose as there are a few publications suggesting same specific to CML and I have personal experience in that it is working for me. Tasigna is an unknown to me but there are trials looking at low dose Tasigna and Gleevec in combination and a study showing low dose Tasigna working in a different leukemia:

 

https://clinicaltria...how/NCT01819389

 

https://www.ncbi.nlm...pubmed/20832858

[cmljax]

Hmmm - so much to ponder.  Good to have options thought.  No good ones 20 years ago. Thanks Scuba.

[Trey]

Trey, My HB has dropped from 55-60 to 35-40 after 9 mos. on 800 mg Tasigna... ...Have you ever heard that Tasigna can play ~tricks~ with your H?

 

Those are not hemoglobin numbers, so I don't understand the question. I suppose Tasigna can play tricks with your hemorrhoids. 

[jjg]

Those are not hemoglobin numbers, so I don't understand the question. I suppose Tasigna can play tricks with your hemorrhoids. 

 

Trey I'm pretty confident jlegakis meant HR (heart rate).

I had a similar decrease in HR the first 2 years I took tasigna. I also have a similar history of extensive exercise and monitoring my HR to gauge recovery from training. Since restarting tasigna post pregnancy it's still in the 40's when my fitness says it should be in the 50's but at least it's no longer hitting the 30's on a regular basis. I also had a clear stress test.

[Pin]

Trey I'm pretty confident jlegakis meant HR (heart rate).

I had a similar decrease in HR the first 2 years I took tasigna. I also have a similar history of extensive exercise and monitoring my HR to gauge recovery from training. Since restarting tasigna post pregnancy it's still in the 40's when my fitness says it should be in the 50's but at least it's no longer hitting the 30's on a regular basis. I also had a clear stress test.

 

Nice problem-solving - must mean "heart beat" = heart rate

[jjg]

Nice problem-solving - must mean "heart beat" = heart rate

 

Being somewhat dyslexic HR and HB look similar enough that I only noticed the difference when Trey asked what it was

[scuba]

Returning to the theme of this thread - I have a Question for Trey:

 

Have you noticed since switching from Gleevec 200mg  to 20mg Sprycel any subtle myelosuppression? Has your CBC remained stable as before or has there been some lowering of blood counts (RBC and WBC specifically)? Thanks

[Trey]

Michael,

I have not had a CBC done long enough after starting Sprycel to know yet.

 

 

I see from previous a post that HB does refer to heart beat, so I will post my answer there also:

http://community.lls...at/#entry195475

 

Trey, My HB has dropped from 55-60 to 35-40 after 9 mos. on 800 mg Tasigna. I feel fine and run 3-4 miles every other day. I've been a long distance runner for decades, but NEVER had a HB this LOW! I am at a CCyR for the last 6 mos. and was wondering IF my onc should lower the doseage to 600mg? A cardiologist had me do a treadmill test and said I dealt with the high intensity well, but I have an electrical STAGE 2 Heart Block that needs to be monitored with EKG'S periodically. He said I have a very strong heart muscle and was NOT very concerned. In fact, he noted that I have a so-called back-up system that acts like a pacemaker! Have you ever heard that Tasigna can play ~tricks~ with your H? It seems that I do NOT have any Qt-Prolongation issues, so what do you think?

 

That is a large drop in heart rate in a short time.  It would seem to be electrical as you indicate.  I would try taking more potassium and magnesium to see if that helps.  This would not be such a problem on Tasigna unless the electrical heart block condition already existed.  But in your case the Tasigna seems to be interfering with the signaling process.  If it were me, I would switch drugs.

 

http://www.hrsonline...ers/Heart-Block

[SandyG353]

Question for Trey.

I remember you stating the odds of losing remission at different periods time after stopping the tki drugs.

You indicated that you were going to stay at 200mg of Gleevec.   What made you change your mind about stopping the Gleevec?  Why did you start Sprycel instead of going back to Gleevec?

Sandy