IM and Grapfruit - Bob

[Guest guest]

Hi Bob,

There are a couple of questions here, and I'll try to answer them both.

> Date: Tue, 17 Jan 2006 15:33:49 -0800

> From: " Bob Semonich " <compt@...>

> Subject: RE: Digest Number 290

>

> Can we conclude that increasing Gleevec in the system with grapefruit is a

> desirable action?

This question was very current when IM (Gleevec) was first approved because

a lot of American insurance companies weren't covering it right away. Taking

liver enzyme inhibitors might have been one way to get more bang for their

out-of-pocket buck. Grapefruit seemed an especially cheap and healthy way to

do it (taking erythromycin should work even better, but doing this over a

long time period would not be cheap nor necessarily safe). Now the question

is coming up again because Medicare and a lot of insurance companies are

starting to reduce their coverage of expensive drugs like IM.

The problem was and is that Novartis has never made available its assay for

testing IM serum levels, and without this it's impossible to know whether

enzyme inhibition is working sufficiently to achieve therapeutic levels on a

lower dose. That's why I was excited to see that a French team has come up

with a new approach to monitoring levels (see below, where I've reprinted my

email from ASH on this), which may get around Novartis' senseless embargo of

their own test.

In your own case it's not a matter of taking a lower than normal dose, of

course, but of whether grapefruit might boost your level even higher on an

already high dose.

> When I was first put on Gleevec, I was drinking a lot of

> citrus juices. grapefruit, orange, Gatorade & water. My WBC stayed around 6

> or 7K. In the fall, cooler weather hit and I dropped the juices and began

> consuming more coffee. My WBC went to 10 to 14 to 19 and today it's 22. My

> Onc also increased me from 600 to 800 but I also contracted a pretty sever

> cold and sinus infection during the last 2 readings. I'm unsure how many

> points the WBC normally jump to fight off a bad infection?

> We took a bone marrow sample today and will get results reviewed on the

> 30th. If I'm losing ground, I see BMT - full or incremental{?} as options

> along with AMN107, BMS-354825, or VX-680 as options to evaluate relative to

> my particular situation.

A WBC of 22,000 is pretty high for even a bad sinus infection, so I'm glad

you have a BMA in the works. If you really have suffered a loss of

hematologic remission, then the options you cite are probably the way to go;

however, given the fact that the WBC started to climb AFTER you stopped

eating grapefruit raises another possibility. Granted, the relationship

could be merely coincidencidental, but it's also possible that your body has

an unusual way of processing IM - either that you absorb it poorly,

metabolize it fast, that your Ph+ cells take it up too slowly, or that they

spit it out too fast. If any of these are true, then all it might take to

get you back into good remission would be a higher EFFECTIVE dose of IM

(which, in this hypothetical scenario, the grapefruit was providing). An IM

serum level would useful, at least for telling what the level in your blood

is and I'd recommend you work to get this done. I believe a couple of the

CML centers in the US are actually able to do IM serum levels now - my

recollection is that it's available at Druker's lab at OHSU, and Sawyers lab

at UCLA, but I'm not certain of this. Maybe others on this list can help

here?

If your blood level is therapeutic there's still the question whether IM is

getting into your leukemic cells and staying there long enough to block

BCR/ABL. There are theoretical ways of testing for this, but I'm not sure

whether any of them are clinically available. If your BMA results show a

need for action, please let me know and I'll query one of the CML experts on

this point.

Best of luck with your results,

R