The Gleevec and CHF issue

[Guest guest]

Hello Folks,

I was not really available during the weekend and am only catching up with

the lists now.

I would like to jump into the discussion about the article showing that

" possibly " Gleevec can cause CHF. First of all, I would like to say that it

is my impression that this article merely warns us of a potential problem

that should warrant further investigation and of course puts the possibility

of CHF while undergoing IM therapy on the radar screens of all our

Heme's/Heme/Onc's. I believe this is a very good thing.

Clearly the primary goal of IM is to stop/stabilize and control the natural

progression of CML. I use all those terms because I am admitting that for

some people it does seem to clearly stop - as evidenced by excellent

response, i.e. sustainable PCRU (albeit while continuing drug therapy).

While in others it stabilizes as is evident by stabilized degrees of log

reductions if not reaching PCRU completely.

If the question is " could possibly IM cause CHF by virtue of the fact that

the scientist in question have determined that ABL serves a purpose in

maintaining healthy heart muscle " . The answer is " yes " , but the study is

not conclusive. However, it is interesting to note, that AMN 107 has been

purported to have a lesser side effect profile than IM because contrary to

IM it inhibits ABL first then PDGFR and, from what I have heard, PDGFR

inhibition " MAY " - not saying it is, be responsible for some of the side

effects some of us have been having issues with. For those of you who do not

know, AMN 107 does have a cardiac side effect profile to the point that

patients with known cardiac problems would be advised against it if

possible, as is understood by reviewing the study protocol. We further note

that Nilotinib as well as Dasatinib patients undergo ECG testing at various

intervals in the study, but primarily in the beginning. This is all a very

good safety precaution and I think shows a good ethical approach to the

clinical design of the study. However, in the end we can and must expect

good care and monitoring by our treating docs, and especially more so in

light of this new information.

It is just my feeling that it is very good and healthy of us all to have

discussions such as this because we need to acknowledge that not all

patients on IM therapy are enjoying the same type of quality of life. Of

note is the recent discussions on edema. Some suffer much more so than

others. This brings up another point, that not all of us are going to be

well serviced by IM. We know from the literature that roughly 20% of us

will fail IM for either reasons of resistance or intolerability.

Intolerability is very subjective whereas resistance is not. In the matter

of intolerability we must all be allowed to freely state our complaint and

issues as this is the only way we can have them properly addressed. Were it

not for side effects, scientists would not be prompted to look for causes.

To me side effects can be deemed to be analogous to saying " where there is

smoke - there is fire " . What we do not know is how bad is the fire? Do we

need to be really concerned about it? Is it something we need to monitor and

be aware of? The side effects tell us something is going on, we need to

listen to it and determine what, if anything related to either the disease

or the treatment is causing it.

There is no reason for anyone of us to suffer un necessarily because we have

difficulty in hearing that what works so well for ourselves doesn't work so

well for the rest of us. There has been a tone on some of the lists lately

which I find a bit discouraging in that we label fellow patients as

" whiners " or maybe even possibly lacking grace for not " sucking " it up and

taking all that comes along with CML and the respective treatments in

stride. In my opinion that is a stance that can be very detrimental to the

overall good of this patient population. It is quite possible that while IM

is a very good drug and has prolonged our lives that it is just not the

panacea we had all hoped it would be. That is not a bad thing either.

Research continues on and additional pathways to curing this disease are no

doubt being explored.

From my perspective, I have found much comfort in knowing and understanding

that inhibiting signaling pathways cannot be done entirely free of risk and

independent of any other impact. The reason being that we do not understand

all that there is to know about this disease. And certainly we patients do

not even know what we do not know about this disease. So, in an effort to

help me manage my own expectations I have taken the approach that we all

need to concede that what works for some of us may not work for all of us.

We celebrate the patients who are now being treated and seemingly have a

good response with Sprycel. For many of these patients not only are they

having a cyto response, they report an improved quality of life. It is not

wrong for any of us to strive to ensure that the issues of quality of life

are properly addressed.

There is no doubt in my mind that as time goes on more information will come

to light about these TKI's (tyrosine kinase inhibitors), and it is very

likely that in some cases it might cause some distress for some of us. A

good analogy for me would be thinking about it as if we are all on a raft

adrift in the ocean. The raft has saved us from the sinking boat, but maybe

the wood used in building the raft cannot withstand a really long ocean

voyage. Which is why finding a cure for CML is still an urgent matter. I

have wondered from time to time (as most of us, if not all of us has) what

are the potential downsides of longer term therapy? I am grateful that

research is uncovering potential drawbacks now because it underscores the

need for finding a cure. The need is less urgent for different types of

patients and this becomes controversial to some. However controversial, it

should not stop us all from thinking about it. It is human nature to want to

know how/why something works or doesn't. Most importantly we all need to

understand that we the patients urged and helped to bring this drug to

market quickly, and with good reason, many of us are still here today

because of it. However, we have to remember that as stated in

another post on another list " We are the data " . This is the price we pay

for still being alive. For most of us, we gladly pay this price. Just for

the record in this months issue of the New England Journal of Medicine, Dr

Sawyers has posted a commentary proving that a new inhibitor under

study for breast cancer causes tumor metastasis elsewhere. So, it is not

only the TKI's for CML that are being examined.

All of this highlights again the absolute need for each and everyone of us

to see and be treated by qualified CML experts who are up to date on the

latest information on this disease and the current and on going research.

Most of you know, I was and in many ways still am a big fan of cycling. It

is very important that this be something to be considered in the future.

Those patients with a good response should be allowed, under a doctors

guidance to cycle, if for no other reason than to allow the body to have a

break. I know I am not going to be looked upon as popular, but I believe

this is a discussion that needs to be had but not here on these lists,

rather with our doctors and the key opinion leaders in this disease. It is

not logical, in my point of view anyway, and granted I am not a scientist

nor doctor, that anyone can stay for years/decades on a cytoxic drug of any

kind without some sort of side effect. I am saying however, that we can

probably all manage ourselves quite well if we know what they might be and

perhaps under what circumstance they may arise.

But I thoroughly agree that stabilizing CML has still got to be the primary

concern objective of treatment. You can recover from CHF, but the prognosis

is really really bad for recovery from blast crisis or acute leukemia.

Additionally, further investigation will tell us what was in the patients

profile that may have predicted that knowing what we know now, they would be

at risk for CHF? I want my doctor to know this, don't you?

I for one am happy for any and all new information that we have access to as

it can only serve to help us all understand this disease and our treatment

better. I do not believe anyone should take the issue of side effects

lightly, as some on other lists have, because they are real and they need to

be dealt with either with adjunctive therapy or in switching therapy all

together when necessary. It is not wrong for us to think that we can have a

decent quality of life,which each of us needs to define for ourselves. We

also need to understand this disease better so that we can proactively

participate in our treatment care plan so that we can, to the best of our

ability, achieve a QOL that fits our own description of it.

How many of you know that patients with Hairy Cell Leukemia are being cured

with IFN? Yes, that is cure as in very long term drug free sustainable

remissions. How many of you know that up to 75% of the patients who develop

APL are cured with a modified version of a vitamin E type substance. How

many of you know that AML in children has a much higher rate of cure with

chemotherapy than ever before. There is no reason why we should have to get

used to having this disease for the rest of our lives. It is not

inappropriate for us to believe that we should hope for and expect more than

just a " functional cure " . I point this out because words like " functional

cure " and long term chronic disease are creeping up in some of the

discussions of late.

Anyway these are just my thoughts for this lovely summer day.

Love and all good things to each and everyone of us!

Cheryl-Anne