38 replies to this topic

[Red Cross Kirk]

Red Cross Kirk, what is your history?  .041 is a very low level.  

 

Here's the link to my "Who are you?" post:  http://community.lls...e-8#entry178094

 

In 2013 (when I was on 400mg)  it seemed I was at a plateau when the PCR was around .4%.  My onc even did another BMB about a year from diagnosis to make sure I was still on track.

 

Maybe my number is 4 and the PCRs will start going down again to the .004 range.  I'd be pretty happy with that!

[garfonzo]

JDP I turtled for 2 years on Tasigna before switching to Sprycel. Finally hit MMR barely a year later on Sprycel.
Funny thing is that when I stayed away from the drink my numbers would increase. When I didn't care and ate and drank what I wanted, my numbers would go down. Not implying a correlation but in general I think stress and time of day can affect absorption. Switching to Sprycel once a day may help avoid eating or drinking things that mess with it.
Now I eat very well and am sure to take my Sprycel several hours before any expected alcohol. Never was a binger, just some wine or a beer or two. I intend to enjoy the fruits of life. Now more than ever. Before CML i didn't do much fun. Now I say yes much more often to adventure and experiences.

[JPD]

Thanks all for the kind words.

 

As I said - Im not good with moderation.  Whether it be beer, video games, relationships, or other hobbies.

 

I wish I were the type that could enjoy a beer here and there & I can do that for a few weeks/months... but eventually I always get in too deep.

 

Again, thanks for the kind words of encouragement.  I'm off the ledge about my numbers... it is what it is - take the pills and live your life. 

[pammartin]

I think you should call the WAAAAAAmbulance

Unnecessary.

[campanula]

I'm bummed too.  A year ago I reduced from Gleevec 400mg to 200mg per day because I was tired of the foot cramps and small hemorrhages on my hands.  Before that my PCR had been going down every time. My March 2015 PCR was .045 and this March it was .041.  I recently asked my onc if maybe I should go up to 300mg per day or maybe change meds.  He hasn't responded yet.  I guess I should just be happy to be where I am.  I don't feel like a turtle anymore, I feel like a slug.

I just saw a CML specialist yesterday who told me that Gleveec dosage <300mg doesn't get absorbed by the body.  She would switch to another TKI.

[Buzzm1]

I just saw a CML specialist yesterday who told me that Gleveec dosage <300mg doesn't get absorbed by the body.  She would switch to another TKI.

If I were you I would get a second opinion ... that's complete BS ... 

[scuba]

I just saw a CML specialist yesterday who told me that Gleveec dosage <300mg doesn't get absorbed by the body.  She would switch to another TKI.

 

Yet, another "CML specialist" who doesn't know what they are doing. This is nonsense (i.e. <300mg doesn't get absorbed).

[Buzzm1]

I'm bummed too.  A year ago I reduced from Gleevec 400mg to 200mg per day because I was tired of the foot cramps and small hemorrhages on my hands.  Before that my PCR had been going down every time. My March 2015 PCR was .045 and this March it was .041.  I recently asked my onc if maybe I should go up to 300mg per day or maybe change meds.  He hasn't responded yet.  I guess I should just be happy to be where I am.  I don't feel like a turtle anymore, I feel like a slug.

Gleevec is best taken with food; avoid "fatty foods" to improve absorption. Acidics, such as fruit juice, improve absorption.  I take a vitamin C with dinner and take Gleevec, an hour, or so, after dinner, with fruit juice.  Works for me.

[Red Cross Kirk]

I just saw a CML specialist yesterday who told me that Gleveec dosage <300mg doesn't get absorbed by the body.  She would switch to another TKI.

Maybe the "CML specialist" meant that not as much is absorbed.  A little while back I was reading an old report about the dosing trials for Gleevec.  I think it said that at a 300mg dose most people showed a good response.  But those on lower doses responded - just not as well.

[scuba]

Maybe the "CML specialist" meant that not as much is absorbed.  A little while back I was reading an old report about the dosing trials for Gleevec.  I think it said that at a 300mg dose most people showed a good response.  But those on lower doses responded - just not as well.

 

Gleevec is a salt (as are the other TKI's) - as such it is absorbed readily. Adding vitamin C or any other "acid" doesn't change anything. 

 

"Imatinib is rapidly absorbed after oral administration with a peak plasma concentration occurring at 2-4 hours [8]. The bioavailability of Imatinib is around 98% which is irrespective of dosage form(solution, capsule, or tablet) or dosage ( 100 or 400 mg) [3,10,11]. Additionally, iImatinib absorption is not significantly affected by food [12]. When given with a high fat meal, the rate of absorption of Imatinib was minimally reduced (only 11% decrease in Cmax and 1.5 hours increase intmax), with a small reduction in AUC (7.4%) compared to fasting conditions [3]. Imatinib is extensively distributed into tissues and is highly protein bound, predominantly to albumin and a 1-glycoprotein (AGP), which is translated into a large volume of distribution ( 435 L) and a long half life (18 h) [11]. The increase in mean Imatinib AUC with increasing the dose was linear and dose proportional in the range 25-1000 mg after oral administration [3]."

 

http://www.omicsonli...77.php?aid=1734

 

Dose response or effectiveness is unrelated to bioavailability. Gleevec is highly bioavailable as noted above.

[Red Cross Kirk]

Dose response or effectiveness is unrelated to bioavailability. Gleevec is highly bioavailable as noted above.

 

But the amount of imatinib absorbed is dependent on dosage.  The point I was trying to make is that the dosing trials found that for most people a 300mg or higher dose was quite good at reducing CML.  Whereas a dose of 200mg or less showed a marked reduction in effectiveness.

[scuba]

But the amount of imatinib absorbed is dependent on dosage.  The point I was trying to make is that the dosing trials found that for most people a 300mg or higher dose was quite good at reducing CML.  Whereas a dose of 200mg or less showed a marked reduction in effectiveness.

 

I was responding to Campanula's post.

 

The amount of Imatinib (Gleevec) "absorbed" is NOT dependent on dosage. ALL of it is absorbed (98% to be more precise) and pretty quickly. I think the point you are making is that ALL of the 300mg absorbed has more effect at impacting CML than ALL of the absorbed 200mg dose. The key here is that absorption is not dose dependent. But effectiveness is dose dependent. One simply needs more Gleevec to be effective than less Gleevec. Absorption is not the issue.

[Red Cross Kirk]

I was responding to Campanula's post.

 

The amount of Imatinib (Gleevec) "absorbed" is NOT dependent on dosage. ALL of it is absorbed (98% to be more precise) and pretty quickly. I think the point you are making is that ALL of the 300mg absorbed has more effect at impacting CML than ALL of the absorbed 200mg dose. The key here is that absorption is not dose dependent. But effectiveness is dose dependent. One simply needs more Gleevec to be effective than less Gleevec. Absorption is not the issue.

Isn't semantics fun?

 

I disagree with the statement "The amount of Imatinib (Gleevec) "absorbed" is NOT dependent on dosage."

 

How about this? - The degree of imatinib absorption isn't dependent on the dosage, but the quantity of imatinib absorbed is dependent on the dosage.

 

And I do agree that Campanula's onc is mistaken if they believe a dose less than 300mg doesn't have an effect on CML.

 

"The increase in mean Imatinib AUC with increasing the dose was linear and dose proportional in the range 25-1000 mg after oral administration [3]."

 

The preceding quote seems to contradict that notion.

 

Does "AUC" mean area under the curve?  That's some statistical thingy isn't it?

[scuba]

Isn't semantics fun?

 

I disagree with the statement "The amount of Imatinib (Gleevec) "absorbed" is NOT dependent on dosage."

 

How about this? - The degree of imatinib absorption isn't dependent on the dosage, but the quantity of imatinib absorbed is dependent on the dosage.

 

And I do agree that Campanula's onc is mistaken if they believe a dose less than 300mg doesn't have an effect on CML.

 

"The increase in mean Imatinib AUC with increasing the dose was linear and dose proportional in the range 25-1000 mg after oral administration [3]."

 

The preceding quote seems to contradict that notion.

 

Does "AUC" mean area under the curve?  That's some statistical thingy isn't it?

 

Red Cross Kirk ... you are quite correct - I re-read my statement and it's not worded the way I intended. Of course the greater the dose, the more is absorbed ... in an absolute sense. So your statement corrects mine.

 

My main point remains, however, whatever dose is taken - 98% of it is absorbed. Whether that amount is sufficient to arrest CML is the topic of study.

[campanula]

But the amount of imatinib absorbed is dependent on dosage.  The point I was trying to make is that the dosing trials found that for most people a 300mg or higher dose was quite good at reducing CML.  Whereas a dose of 200mg or less showed a marked reduction in effectiveness.

 

 

I was responding to Campanula's post.

 

The amount of Imatinib (Gleevec) "absorbed" is NOT dependent on dosage. ALL of it is absorbed (98% to be more precise) and pretty quickly. I think the point you are making is that ALL of the 300mg absorbed has more effect at impacting CML than ALL of the absorbed 200mg dose. The key here is that absorption is not dose dependent. But effectiveness is dose dependent. One simply needs more Gleevec to be effective than less Gleevec. Absorption is not the issue.

Hmmm...I think we are all talking about the same thing, more or less.  She used the word "absorb" and my takeaway was that 200mg Gleevec moved through the system too quickly for enough of it to be absorbed by the body.  But what she very well could have meant was that anything below 300mg is not as effective.  (She is well-respected at a nationally recognized institute and is conducting a TKI cessation clinical trial.)

[JPD]

Scuba - is the same true with Tasigna?  Could alcohol even interfere with the absorption and/or potency of the Tasigna? 

 

Dont worry, Im still gonna stop drinking (3 days - easy peasy)

[Red Cross Kirk]

Hmmm...I think we are all talking about the same thing, more or less.  She used the word "absorb" and my takeaway was that 200mg Gleevec moved through the system too quickly for enough of it to be absorbed by the body.  But what she very well could have meant was that anything below 300mg is not as effective.  (She is well-respected at a nationally recognized institute and is conducting a TKI cessation clinical trial.)

 

I think she meant the latter.  Here's an old chart that shows dose vs. response:

 

 Imatinib Dose Chart.jpg   33.14KB   2 downloads

 

It's from this article:

Efficacy and Safety of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in Chronic Myeloid Leukemia

Brian J. Druker, M.D., Moshe Talpaz, M.D., Debra J. Resta, R.N., Bin Peng, Ph.D., Elisabeth Buchdunger, Ph.D., John M. Ford, M.D., Nicholas B. Lydon, Ph.D., Hagop Kantarjian, M.D., Renaud Capdeville, M.D., Sayuri Ohno-Jones, B.S., and Charles L. Sawyers, M.D.

N Engl J Med 2001; 344:1031-1037April 5, 2001DOI: 10.1056/NEJM200104053441401

 

[thatguy]

I figured my liver needed a break since the TKIs are so hard on it. It was a personal choice. I will say my life is much better off caffeine. No more midday slumps.

This^. My theory: If it comes to transplant time, you want those kidneys, liver, pancreas, heart and other important items, tip-top.

[scuba]

Scuba - is the same true with Tasigna?  Could alcohol even interfere with the absorption and/or potency of the Tasigna? 

 

Dont worry, Im still gonna stop drinking (3 days - easy peasy)

 

JPD - In your case - it doesn't matter, just stop drinking completely. You write that you can stay away from alcohol - so best just to stay away from it since it controls you if you imbibe.

 

Switch to Pellegrino or Avian or some other non-alcoholic drink. Then there will be no issue with Tasigna.