ASCO Release, Dr. Heinrich's Plenary Talk, Dosage

[Guest guest]

This press release is just out regarding Heinrich's presentation at

the American Society of Clinical Oncology (ASCO):

http://www.ohsu.edu/ohsuedu/newspub/releases/051605Gleevec.cfm

At the talk, Dr. Heinrich stated that regarding the 400 mg versus 800 mg

dosage of Gleevec arms of the randomized phase III trial, there were no

differences in response rates.

PORTLAND, Ore. - Patients with gastrointestinal stromal tumors (GIST) who

have a particular genetic mutation are more likely to respond to Gleevec

(imatinib) than those without the mutation, according to OHSU study results

showcased at the 2005 annual meeting of the American Society of Clinical

Oncology (ASCO). The results confirm previous observations and provide a

foundation for molecular testing that can predict who will best respond to

treatment with Gleevec.

" Increasingly, there will be more drugs like Gleevec that are very

specific in their action, and patients' responses to them will be dictated

by their tumor biology, " said C. Heinrich, M.D., principal

investigator of the study. " Performing molecular tests on patients' tumors

will be useful for doctors in determining how patients should be treated. "

Heinrich is a professor of medicine (hematology/medical oncology) in the

OHSU School of Medicine and the Portland Veteran Affairs Medical Center

(PVAMC) and a member of the OHSU Cancer Institute.

Gastrointestinal stromal tumors, which occur in the stomach and

intestines, are diagnosed in about 5,000 Americans annually. Surgery is the

treatment of choice for localized tumors, but in many patients the tumor

recurs and spreads elsewhere, particularly to the liver. Without Gleevec, at

this metastatic stage the disease is rapidly fatal because chemotherapy,

radiation and surgery are ineffective in advanced cases.

Gleevec works by inhibiting a protein called KIT, which is abnormally

expressed in GIST and fuels tumor growth by signaling cancer cells to keep

growing. The majority of GIST patients have dramatic clinical improvement in

their disease (tumor shrinkage) after beginning treatment with Gleevec.

However, more than half of patients develop resistance to the therapy and

experience disease progression after about two years.

In a previous study, Heinrich and colleagues identified differences in the

clinical response to Gleevec among patients with different mutant forms of

KIT protein, which is a type of tyrosine kinase. The purpose of this latest

study was to further examine the relationship between the more common

mutations and drug response in a much larger, dosage comparison Phase III

study.

" We are pleased that the findings in this study substantiate our earlier

observations, " said L. Corless, M.D., Ph.D., who collaborated

with Heinrich on the study. " Molecular subtyping of GISTs is clearly

important to understanding how Gleevec - and other drugs in the pipeline -

affect growth signaling in these tumors. " Corless is a professor of

pathology in the OHSU School of Medicine and PVAMC and a member of the OHSU

Cancer Institute.

Researchers analyzed tumor DNA samples from 324 GIST patients, obtained

before they began treatment with Gleevec, and correlated the findings with

subsequent patient outcome. Of 280 tumors with abnormalities of the KIT

gene, those with a mutation in a segment called " exon 11 " were significantly

more likely to have a clinical response to Gleevec than patients whose tumor

had a KIT " exon 9 " mutation or had no mutations. Patients with the KIT exon

11 mutation responded to Gleevec for a longer period (576 days) than those

with the KIT exon 9 mutation (308 days).

" However, there was no difference in the likelihood of clinical response

between the two doses used in the study, " said Heinrich. " The presence of an

exon 11 type mutation was the single best predictor of clinical response to

Gleevec, irrespective of dose. "

The study also confirmed that new drugs are urgently needed for patients

whose GIST genotype is less responsive to Gleevec. In response to this

clinical need, future studies planned by Heinrich and colleagues will

evaluate the use of Gleevec in combination with other agents to treat GIST

patients.

" We have a powerful tool in Gleevec, " said Heinrich. " However, we need to

find ways to use the therapy so it doesn't just shrink tumors, but totally

eliminates the cancer cells, so the tumors don't come back. "

The OHSU Cancer Institute is one of only about 60 National Cancer

Institute-designated cancer centers in the nation and remains the only such

center between Sacramento and Seattle. It comprises some 120 clinical

researchers and basic scientists who are working together to translate

scientific understanding into longer and better lives for cancer patients.

[Guest guest]

Hi Zavie,

Thanks for sending this along. I haven't had a chance yet to look

anything up from ASCO. (A friend of mine went and she is a cancer

researcher, so I may need to pick her brain.)

However, I'm confused. The press release is about GIST, not CML, and I

don't believe you can extrapolate. So what dosage difference are you

referring to? Are you referring to something different and not the press

release? There has been plenty of research indicating that higher doses,

in CML, are better.

How are you doing lately?

jennifer g.

www.cmlsupport.com

[ ] ASCO Release, Dr. Heinrich's Plenary Talk, Dosage

This press release is just out regarding Heinrich's presentation

at

the American Society of Clinical Oncology (ASCO):

http://www.ohsu.edu/ohsuedu/newspub/releases/051605Gleevec.cfm

At the talk, Dr. Heinrich stated that regarding the 400 mg versus 800 mg

dosage of Gleevec arms of the randomized phase III trial, there were no

differences in response rates.

PORTLAND, Ore. - Patients with gastrointestinal stromal tumors (GIST)

who

have a particular genetic mutation are more likely to respond to Gleevec

(imatinib) than those without the mutation, according to OHSU study

results

showcased at the 2005 annual meeting of the American Society of Clinical

Oncology (ASCO). The results confirm previous observations and provide a

foundation for molecular testing that can predict who will best respond

to

treatment with Gleevec.

[Guest guest]

Hi ,

The 400/800 dose was only mentioned in the talk. It doesn't appear in the

published paper.

The paper was about GIST and not CML and of course you cannot extrapolate.

We do know that with CML it sometimes takes an 800 mg dose to reduce the

Phillies.

I am one of those people who is not yet been convinced (no data) that once

you have achieved CCR at the 400 mg dose it is not important to increase the

dose to achieve PCRU, particularly if QOL is reduced..

I am doing quite well and hope that you are able to manage with the Gleevec.

Zavie

[ ] ASCO Release, Dr. Heinrich's Plenary Talk, Dosage

This press release is just out regarding Heinrich's presentation

at

the American Society of Clinical Oncology (ASCO):

http://www.ohsu.edu/ohsuedu/newspub/releases/051605Gleevec.cfm

At the talk, Dr. Heinrich stated that regarding the 400 mg versus 800 mg

dosage of Gleevec arms of the randomized phase III trial, there were no

differences in response rates.

PORTLAND, Ore. - Patients with gastrointestinal stromal tumors (GIST)

who

have a particular genetic mutation are more likely to respond to Gleevec

(imatinib) than those without the mutation, according to OHSU study

results

showcased at the 2005 annual meeting of the American Society of Clinical

Oncology (ASCO). The results confirm previous observations and provide a

foundation for molecular testing that can predict who will best respond

to

treatment with Gleevec.