Leukemia May Build Resistance to Drug

W A S H I N G T O N, June 22 -- Two factors — a geneticmutation and the excessive production of a key enzyme — havecaused some patients with very advanced leukemia to developresistance to the new anti-cancer drug Gleevec, scientists saidThursday.

Dr. Charles Sawyers, a cancer doctor at the Jonsson CancerCenter at the University of California at Los Angeles who led theresearch, said this discovery of why Gleevec failed to beat thedisease in very ill patients could point the way towardstrategies to combat resistance to the drug.

He emphasized the findings, published in the journal Science,do not diminish the value of Gleevec as a weapon against chronicmyeloid leukemia (CML). The drug, made by Swiss drug manufacturerNovartis AG (NOVZn.S), is known as Glivec outside the UnitedStates.

"In no way does this discredit or dampen enthusiasm for thedrug," Sawyers said in a telephone interview.

"This is an amazingly good drug. There are now thousands ofpatients being treated with the drug, and resistance is a veryrare phenomenon in patients who are still in the chronicphase," before the cancer turns more vicious.

The U.S. Food and Drug Administration on May 10 approvedGleevec for use against CML. It also is being studied for use intreating other cancers.

CML, which generally strikes middle-aged people, is amalignant cancer of the bone marrow that causes rampant growth ofblood-forming cells. After about five years of a chronic phase,the disease develops into an end-stage "blast crisis" thatusually kills patients in two to six months.

Gleevec, formerly known as STI-571, can cause remission ofthe cancer by inhibiting an enzyme produced by an abnormal genecalled BCR-ABL that generates cancer cell growth.

In patients in the chronic stage of this type of leukemia,remissions brought about by treatment with Gleevec appeared to bedurable, the researchers said. But they also noticed that whilepatients in the final stage initially went into remission usingGleevec, a relapse often followed.