Genetic mutation improves anticancer drug's effect

Washington, June 18 : Oncologists at Ohio State University have found that a gene mutation responsible for some cases of acute leukaemia can even improve the effect of a specific anticancer dug, called cytarabine, on this disease.

Led by Dr. Clara D. Bloomfield, an internationally known AML specialist at the Ohio State University Comprehensive Cancer Center, the findings of this Cancer and Leukaemia Group B clinical cooperative group study may also change the way doctors manage these patients.

This retrospective study also shows that people with acute myeloid leukaemia (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.

The study also indicated that testing for RAS mutations might help doctors in identifying which AML patients should receive high-dose cytarabine as their post-remission therapy.

"This appears to be the first example in AML of a mutation in an oncogene that favorably 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 post-remission therapy rather than a stem-cell transplant," said Bloomfield.

Bloomfield said that usually, people with newly diagnosed AML are treated first with drugs aiming to drive the disease into complete remission. After this, patients are given additional chemotherapy, such as high-dose cytarabine, or more aggressive therapy, such as a stem cell transplant, to prevent relapse and to cure the malignancy.

However, high-dose cytarabine proves to be a better therapy for some patients, and the study's findings may enable doctors to identify those individuals.

For the study, the researchers examined the outcome of 185 AML patients at or less than 60 years of age, who had achieved complete remission following initial therapy.

They found that 34 of the patients (18 percent) had mutations in the RAS gene, and of these, 22 received high-dose cytarabine and 12 received the drug at low dose. The high-dose patients with RAS mutations had the lowest relapse rate - 45 percent experienced disease recurrence after an average 10-year follow-up compared with 68 percent for those with normal RAS genes.

"That means fifty-five percent of patients with RAS mutations were cured compared with 32 percent of high-dose patients with normal RAS," said Bloomfield.

Of patients who received low doses of the drug, those having the mutations relapsed, as did 80 percent 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 Bloomfield.

The research is published online in the latest issue of the Journal of Clinical Oncology with an accompanying editorial.

ANI