8 replies to this topic

[ROM1212]

Seeing all the different posts about dosages being upped or reduced made me wonder something.  Even though this is impossible, suppose two different people are the same in every way, same sex, stage of CML, same BCR-ABL %, same age, same level of G absorption, etc.  If one person was 6-5, 250-lbs., compared to the other who is 5-7, 150 lbs., does G have a greater effect on the smaller person because per pound, the percentage of medicine is greater throughout the body?  Likewise, would a person's skeletal frame ("big-boned" vs. a lighter frame) influence the effect of G?

I know everybody is different and no two are the same, but I've wondered if this could cause some people to experience different side effects if the level of G "concentration" is different?  Isn't this why common medicines have differing dosages based on age (and I suppose body size)?

[everonward]

Hi

I'm not sure G works like that but has other factors that may mark its effectiveness.

I was dx Oct 05 so not too short of 4 years now. I'm 5'2" and 57kg (approx 125 lbs) and my PCRs have a constant theme of around 0.2% which my onc (Dr Ho) a well respected member of the CML community is happy with, Although to get a full blown 3 log it should be 0.08 at King's - I had one done in Germany on International scale which came in at 0.05.

I have virtually no side effects - some leg pain, feeling the cold more, a little puffiness around the eyes, often due to a night out. BTW I find the new Garnier caffine eye roll on really helps there. I have also had some weight gain- about 3 kg over by my 'normal' mark - but as I've3 just turned 50 it could be a menopause symptom.

Dr Ho is running a test to check my Glivec residual levels - taken at trough period. \i should have the results in a week or two along with my latest PCR I'll let you know.

ATM

[Trey]

The issue of body weight and Gleevec dosage requirement is an interesting one. The Japanese have done some work on this issue because of their smaller average size and weight. They have gathered information that they believe shows some correlation, mainly because people with lower body weight tend to have increased side effects, especially myelosuppression (low blood counts). But there is more work that needs to be done on this.

Here also is an article that says smaller people "clear" Gleevec more slowly from their system than larger people. If the body clears the drug more slowly, the build-up is greater due to the long half-life (roughly 18 hours) of Gleevec in the body. www.liferaftgroup.org...study_Gleevec_levels.html

The issue might be a combination of lower amount of blood and tissue by weight and lower liver weight. Also, a smaller liver would presumably clear the drug more slowly from the body than a larger liver. This is mainly conjecture. Again, more work needs to be done to confirm a correlation between body weight and dosage.

[ROM1212]

Trey, that is good info.

If smaller people "clear" Gleevec more slowly from their system than larger people, and a smaller liver is clearing the drug more slowly, does this increase the potential for toxicity?  How is toxicity recognized?  I'm not Japanese but I'm not a large person, either.

Thanks for all your help.

[rct]

It has sadly been our experience that toxicity is barely recognized, if at all.  It isn't quantified, it isn't addressed beyond minor mention at the beginning of any seminar, discussion, or doctors visit.  In short, they don't care about toxicity and/or its effect on your life, they only care that there is a response to cancer because that's what oncologists do.  The rest is up to yer GP, which of course we all know, they won't do anything for fear of wrecking what the oncologists are doing.

My CML'r is PCRu, and that is all that matters to the oncs.  At this time, today, my CML'r would rather have the leukemia back than the Gleevec/Neupogen ride that is a year long next month, the side effects and toxicity of injecting yerself with e-Coli every week on top of the side effects and toxicity of Gleevec is so bad.  And they literally look us in the eye and say "...PCRu, so we're happy!".

That's all they got.  So, good luck with that correlation to weight.  I'd probably bet a dollar ain't nobody looking into anything that deals with toxicity.  And ruin their miraculous work?  The heck you say!

So we'll move along, see what others have to offer.  Problem is, no matter how bad it is each day though the weekly cycle, we know that it is in fact "working", if by "working" you mean spectacular response but some pretty dismal side effects.  And it is hard to call myleosuppresion a side effect, it is more like...a problem than a side effect.  Is it worth changing?  Don't know.  Three years plus with Gleevec and PCRu is pretty hard to give up in the face of the problems one can have changing these chemos.  Should wait until, hopefully never happens, it doesn't work anymore, right?  Should wait until, hopefully does happen, myleosuppresion stops, right?

I think the biggest thing for everyone here is that it seems to us and to the oncs that the response to Gleevec, both oncological and side effectualizational, yes I did invent that word, just now, is so individual that stats are becoming nearly meaningless, and so predictability is becoming foggier.  That sucks.  Repeatable would be great, and if not repeatable why not repeatable would be enormously helpful but it just doesn't happen that way.

I think of you all, and all of the things you all have to do, every day.  I hope everyone gets through it.  I wish I could take all of you to Disney World.  We could have a beer.

rct

[everonward]

I'm sorry to hear that your CML'er is having such an awlful time of it. However, your story has made me re-assess my own situation with my onc. My pcr floats at around 0.2% so I was pushing for an increae from my 400g of G. He refuses point blank. He says that studies now show someone who sustains a low level for a number of years has as good an odds as someone at PCRu and that any increase in side effects (I am very lucky my only side effects are a little eye puffiness in the morning for half an hour and the ocassional leg pain) would out weight any benefits from a lower PCR count.

Listening to what you are going through has helped me to understand where he is coming from. Thank you.

[rct]

Yes absolutely.  It is interesting to see all of the "competition" to get to some figure on paper such as three log, PCRu, whatever it might be this week or next month of last year.  Fact is, low numbers, long time, minimal side effects are absolutely the best anyone can do.  Our PCRu appeared out of the blue, but with numbers down past decimal point followed by 5 zeros, it wasn't really a suprise. And it won't be a surpise to us at all, nor a catastrophe, if the next one is not PCRu, such is the nature of this stuff.

Nobody knows what log reduction or what measure of PCRu is right, since people from all levels of response on down to undetectable have had the worst happen to them, no number is any guarantee of anything.  I am glad your number is that low on 400 and that you are having mininmal side effects and I hope it stays that way for you for a long, long time.  That is something like our oncs approach to this mess, and my writing here was more venting for the two of us than anything.  Nobody really understands what you folks are going through except, well, you folks.  Stupid oncs don't even know really.  Heh.  I said "stupid".

rct

[Trey]

A liver has two main functions.  It is generally a filter, but also produces bile to aid digestion of fats.  A smaller one needs to work harder to "clear" the same volume of a substance.  So it would likely be more prone to be damaged if it is working harder.

Toxicity is generally recognized by testing (Comprehensive Metabolic Panel test, or Liver Panel Test).

www.medicinenet.com/drug_induced_liver_disease/article.htm

http://en.wikipedia.org/wiki/Hepatotoxicity

[RhettC]

ROM

I had the same question....I'm 6'3" and 215. My Gleevec level at 400G was 811 . That's within the guidelines but Specialists like Dr Drucker like to see a level at or around 1000.

Dr Drucker says there are a lot of factors that impact levels but size is not one of them .