18 replies to this topic

[CML***]

It happened to me, and I have lived to tell about it! 

[hannibellemo]

Wow, Mary, that is quite a story and no, they are not just "black box warnings". They are there because those drugs have been lethal and some point during testing or after. Fortunately it does not effect a large percentage of people. Unfortunate, because you now number yourself among those it does affect.

 

I don't think you really need to spend much time worrying about mutations though at the low PCR level you were at before the drug reaction and subsequent TKI break. 

 

I'm glad you are recovered and doing so well. Thanks for sharing your experience with us!

[JPD]

Think Ill demand an EKG this Friday when I see my Onc

[rcase13]

I have my three month tomorrow. You can bet I will ask for one. So far I have gotten one every time I have gone in. Very glad you were able to recover.

I am shocked the doctor only did the one.

[JPD]

Ive only be Dx since 11/2013, but Ive probably had 6 or 7. 

[Billie Murawski]

Dear Mary, 

 What an awful experience for you and your family I can understand what they went through. Thank you for sharing that with us. So many people get warning signs but they just dismiss them as side-effects. As far as Tasigna goes my cardiologist said I could never go on that. I'm so glad you are better now. Keep us updated on how you handle bosulif,I'ts so scary going on a new med. Hopefully I can stay on Sprycel, I have my ups and downs but at least I know some of what to expect so I don't panic so much, I just keep telling myself that not every problem is tki related.

Pam Martin was just put on bosulif, she had major problems with Sprycel so she is terrified of taking anything.(I don't blame her). She received her bosulif a few days ago and last I heard from her she was sitting on the floor in the corner, just staring at the bottle. I still don't know if she took the pill.

         I'm so glad you pulled through.   Billie

 

 

 

 

 

[MCPO]

I am so glad you are ok.  That is my biggest concern with Tasigna and I am frustrated that "regular EKG's" are recommended, but the drug companies don't define what "regular" means.  Some oncologists interpret that to mean annual, others every 3 months, others ignore it.  I am also surprised insurance companies haven't forced oncologists and Tasigna to define "regular" as they are the ones footing most of the costs.  

[Trey]

Mary,

Did any of your EKG tests show an elongated QT interval, either before or after the event?

[Trey]

An interesting and important story.  Glad you are doing well now.

 

My question about EKG's before the incident was whether any of your previous EKGs at any time showed QT prolongation.  I assume you had one prior to starting Tasigna.  The question relates to whether EKGs are predictive or not for this issue while taking Tasigna.  That would be significant for those taking Tasigna and relying on EKG tests as an indicator of vulnerability.

[Trey]

I don't know if this applies to your case, but it is interesting that you previously had a hyperactive thyroid (Graves Disease) for which you had radioactive iodine treatment, which permanently "degrades" the thyroid to induce the opposite condition, i.e., hypothyroidism.  TKI drugs can also induce hypothyroidism.  So you could have a multiplying effect on your thyroid.  The thyroid plays a significant role in heart function:

http://circ.ahajourn...16/15/1725.full

 

High fat meals (Thanksgiving) increase the effects of the TKI drug in the body.  This is why Tasigna dosing instructions require no food consumption.  Also, hypothyroidism significantly raises lipid levels (fats) in the bloodstream.  And since Tasigna has a relatively long half life in the body (about 17 hours) any compounding effects can happen more easily than with Sprycel which has a much shorter half life (about 5 hours).

 

Again, I do not know if this applies to your case.  Maybe it was just random.  But it may be worth discussing with your doctors whether Tasigna is the right TKI given your medical history of thyroid issues.

[MCPO]

Trey, that's interesting that Tasigna has a longer half life than Sprycel...I assumed it was the opposite, since Tasigna is a twice a day drug. My local oncologist mentioned that he thinks Sprycel is more potent than Tasigna.  Which I never really understood his remark.  Sprycel was giving me bleeding issues, but now I'm thinking that's the better of the two evils.   I'm questioning often if switching to Tasigna was the right move, rather than just lowering my Sprycel dose to 50mg.  I have questioned whether EKGs are truly predictive in nature of prolonged QT syndrome.  It seems like we don't know the answer to that.  Does anyone know how long EKGs have been part of the treatment protocol with Tasigna?  

[Trey]

The FDA required a black box warning about QT and also required EKG instructions as a condition of Tasigna approval.  The split dosing was also related to the QT issue.  The FDA EKG instructions were:

"EKG's should be obtained to monitor the QTc at baseline, seven days after initiation, and periodically thereafter"

The term "periodically" was not defined.  I think the "seven days after" has been ignored in many cases, but that would be a very informative time to show Tasigna effects on QT.

 

The FDA also said Tasigna should not be used in patients with low potassium or magnesium.  These are related to heart signaling, and Tasigna can reduce levels of these minerals in the body.  So by inference testing of these mineral levels should also be done.  So QT is not the only issue related to the heart.  Low mineral levels can cause arrhythmia due to weakened signals.

 

Regarding drug "potency" that is not an accurate term for comparing TKI drugs.  Each TKI drug either works well for an individual or not, and we are all different.  So a TKI should be described by its effectiveness for each individual patient.

[MCPO]

Thanks for that, Trey! 

[MCPO]

Sprycel also has a Prolonged QT risk, is that correct?  But, just not as high as Tasigna?  Did I imagine that.  I can't seem to find where I saw that right now.  My MD Anderson CML specializing oncologist told me drinking black coffee during the fasting window with Tasigna was fine, but I'm wondering if caffeine is a bad idea. 

[Trey]

Tasigna and Sprycel are probably not much different regarding QT issues.  All TKI drugs carry some QT risk.  Studies have shown this may be a significant issue for about 1% of patients.

 

Tasigna dosing instructions:

Nilotinib may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can infrequently result in serious (rarely fatal) fast/irregular heartbeat and other symptoms

http://www.rxlist.co...precautions.htm

Sprycel dosing instructions:

"Dasatinib may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can infrequently result in serious (rarely fatal) fast/irregular heartbeat and other symptoms.."

http://www.rxlist.com/sprycel-drug.htm

 

Note that the dosing instructions are EXACTLY the same for both.

 

The issue is that Tasigna had several cardiac "events" occur during clinical trials, including a couple sudden deaths (heart related, but NOT known if it was QT related).  Sprycel also had cardiac events but not as many and not as significant.  The clinical trial participants often have issues going in which can make them higher risk, and a number of those in the various trials had serious pre-existing heart conditions and may have been taking other drugs which compound the risk.  A clinical trial has many variables among its participants.  But all events must be reported.  The Tasigna trial seemed to just have the bad luck there. 

 

A key point here is that the reason for the QT prolongation related to TKI drugs is not exactly known.  It is probably not a direct relationship with the heart, but rather an indirect relationship through the endocrine system (thyroid, etc), and that also indirectly through lowered mineral (potassium, etc) levels.  Low potassium also causes muscle spasms and cramps throughout the body, and the heart is not immune to muscle spasms.  Potassium also plays a key role in heart timing related to electrical signaling.

 

I do not want Mary's message to be lost or minimized in this discussion.  My purpose is not to say that I know what is happening in any specific case, just to give some suggestions about asking the docs what to do to avoid future events.  Personally, I take extra potassium and magnesium, especially in the summer when I am active outdoors and sweat a lot.  I know for certain it helps with muscle cramps.  I believe it would be a good idea for anyone with heart arrhythmia or QT issues.

 

I would not be concerned about drinking coffee or tea during the fasting window.  The primary concern is that people will eat a high fat meal with Tasigna which raises the drug blood plasma levels for most drugs, including Tasigna, so they warn to eat nothing since they do not trust patients to sort out the foods.

Edited by Trey, 10 January 2015 - 03:19 PM.

[klf2013]

Trey,

I love reading your posts! They are very helpful and answer so many questions for me! Some that I didn't even know i had.

 

What is your take on the use of BMB versus the PCR blood test as a measure of response. At my August appointment my Onc said the PCR is the preferred test and many docs are not using BMB as much. At my December appointment, he changed his tune and said BMB is the only true measure for checking the body's response. I know the research is always evolving, so I was curious if you had any info on this.

Thanks,

Kara

[Trey]

In terms of just accuracy, BMB is most accurate, FISH is second, and PCR third (last).  BMB and FISH are actual counts of leukemic cells, and PCR is an estimate based on small strands of DNA (actually RNA). 

 

But BMB and FISH only measure down to CCyR, which is roughly 1% PCR.  After CCyR the PCR is the only option. 

 

Overall BMB is necessary for diagnosis, after that doing FISH is preferred until CCyR (BMB painful and expensive), then PCR after that.  Many Oncs also do PCR and FISH from the beginning, which is a reasonable idea for creating trend history.

[klf2013]

In terms of just accuracy, BMB is most accurate, FISH is second, and PCR third (last).  BMB and FISH are actual counts of leukemic cells, and PCR is an estimate based on small strands of DNA (actually RNA). 

 

But BMB and FISH only measure down to CCyR, which is roughly 1% PCR.  After CCyR the PCR is the only option. 

 

Overall BMB is necessary for diagnosis, after that doing FISH is preferred until CCyR (BMB painful and expensive), then PCR after that.  Many Oncs also do PCR and FISH from the beginning, which is a reasonable idea for creating trend history.

Thank you!!

[Billie Murawski]

Hi Mary,

I'm so sorry that you and your family had to go through all that and thank God you're doing so well now.

My husband went to the cardiologist today, one of the first things he did was an ekg, it took all of 5 seconds. It really angers me that when you're put on a med that could affect your heart, why don't they do an ekg every time you have an appt(like every 3 months.) I know that medical equiptment is expensive,but in the long run the doc would get paid for the ekg instead of the hospitals. Any time I have a simple outpatient procedure I always have to get an ekg I live in the country so I always have to go all the way into town to the hospital give them my life story and wait for about a half hour for a five second test. Uggh!

 Thanks for the info and keep in touch and let us know how you are doing.   Billie