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Title: Gene Mutation Improves Leukaemia Drug's Effect
URL: http://www.pslgroup.com/dg/223C7A.htm
Doctor's Guide
June 18, 2008

COLUMBUS, Ohio -- June 18, 2008 -- Gene mutations that make cells cancerous can sometimes also make them more sensitive to chemotherapy. A new study led by cancer researchers at Ohio State University shows that a mutation present in some cases of acute leukaemia makes the disease more susceptible to high doses of a particular anticancer drug.

The findings, from a Cancer and Leukemia Group B clinical cooperative group study led by Clara D. Bloomfield, MD, Ohio State University Comprehensive Cancer Center, Columbus, Ohio, could change how doctors manage these patients.

The research analysed the outcome of 185 acute myeloid leukaemia (AML) patients aged 60 or younger who had achieved complete remission following initial therapy. Thirty-four of the patients had mutations in the RAS gene and, of these, 22 received high-dose cytarabine and 12 received the drug at low dose.

The retrospective study showed that people with AML whose leukaemic cells have mutations in the RAS gene are more likely to be cured when treated after remission with high doses of the drug cytarabine. It also suggested that testing for RAS mutations might help doctors identify which AML patients should receive high-dose cytarabine as their postremission therapy.

"This appears to be the first example in AML of a mutation in an oncogene that favourably modifies a patient's response to the dose of a routinely used chemotherapeutic drug. If confirmed, AML patients in the future will likely be screened for RAS mutations, and those who have one may get high-dose cytarabine for postremission therapy rather than a stem cell transplant," Dr. Bloomfield said.

But high-dose cytarabine is the better therapy for some patients, and the findings of this study may enable doctors to identify those individuals. The high dose patients with RAS mutations had the lowest relapse rate -- 45% experienced disease recurrence after an average 10-year follow-up compared with 68% for those with normal RAS genes.

"That means 55% of patients with RAS mutations were cured compared with 32% of high-dose patients with normal RAS," Dr. Bloomfield said.

Of patients who received low doses of the drug, all those with the mutations relapsed, as did 80% of those with normal RAS genes.

"These data strongly suggest that mutations in RAS influence the response of AML patients to high-dose cytarabine, and they support the use of these mutations as biomarkers for this therapy," said Dr. Bloomfield.


SOURCE: Ohio State University Medical Center

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