Low dose of IM - Cam

[Guest guest]

> Posted by: " Cam " coralee.williams@...

>

> Mon Jan 15, 2007 2:22 pm (PST)

>

> Hello everyone,

>

> Right now my doctor has me on 200mg of Gleevec due to low blood counts. I want

> to convince him that I need a higher dose. Where can I find articles or info

> where some top cml doctors have said that low doses are not good? I have been

> looking online but I can't seem to find anything.

>

> Cam

Cam,

It is possible that due to a slowed metabolism or some other mechanism, you

could be achieving a therapeutic serum level if IM (Gleevec) on 200mg/ day.

In that case you're at no greater risk of resistance than are those of us

who take 400mg/day. Not only that, but you'd be achieving the same efficacy

at half the cost and, potentially, half the side effects!

Moreover, I know of no actual evidence that taking less than the standard

dose of IM (Gleevec) causes resistance. HOWEVER (and this is a big

however), if your IM serum level is sub-therapeutic, there are still strong

theoretical reasons to be concerned that resistance could become a problem

over time.

When IM was first approved, Novartis asserted that serum levels hardly

varied from patient to patient, and for this reason (and probably others

which they haven't revealed) they have refused, until recently, to make

their test for IM serum level available. A number of senior CML researchers,

including Druker, feel this is misguided, and I agree, Fortunately, I

gather that recently Novartis has indeed released the test to some centers,

but it's my opinion that the test should be made available to ALL patients

who can't tolerate standard doses (and also for patients who experience a

suboptimal response at 400mg. It may be that a subset of these patients

just don't get enough of the drug into their bloodstream, rather than having

resistant or insensitive CML cells. If the former, there are probably safer

and easier ways to achieve therapeutic levels than doubling the IM dose - so

for in these cases too, serum levels would be desirable). Anyway, you might

find out whether your doctor has access to the newly available serum levels.

If so, and you could determine that your IM serum level was therapeutic on

200 mg, then you'd be home free on that dose.

It's more likely that this is not the case, however, and that you simply

can't tolerate 400 mg. Two other options are still available to you if

that's the case. The more conventional and almost certainly the preferable

one would be a switch to Sprycel.

If you couldn't tolerate this drug either though, you might then consider a

pulse regimen, which might well be just as tolerable as a continuous low

dose such as you're now on, and (I firmly believe) more effective and safer.

Here's how, if I were in your shoes and in control of my own management, I

would go about designing such a regimen:

First, I'd stop IM altogether and follow weekly CBCs until my blood counts

(red or white, whichever are most troublesomely suppressed) rebounded to a

reasonable level. Then I'd restart at 400mg and continue until the counts

dropped too far, then stop again. I would repeat cycle this AS LONG AS I

could stay on IM for at least one, and preferably two months at a time ---

AND as long as I were regularly able to keep my breaks to six weeks or less.

Treatment periods less than a month might be to short to kill leukemia

cells, while drug holidays longer than 6 weeks might give the disease long

long enough to start relapsing.

So there you have my two bits. I hope you find them useful - or at least

interesting!

R