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New Leukemia Drug Overcomes Gleevec Resistance

A study finds 90 percent of resistant CML patients responding to AMN107

TUESDAY, April 19, 2005 (HealthDay News) -- A new compound may offer an alternative treatment for people with chronic myeloid leukemia (CML) who are resistant to treatment with the drug Gleevec, according to two studies presented at the annual meeting of the American Association for Cancer Research, in Anaheim, Calif.

Although Gleevec has helped extend the lives of many patients with CML, others have suffered a relapse after developing resistance to the drug. In some other patients with advanced CML, Gleevec has failed to produce durable cancer remission.

Gleevec works in CML patients by selectively deactivating Bcr-Abl -- an enzyme that triggers the rapid growth of leukemia cells. However, some patients develop mutations in the Bcr-Abl enzyme, resulting in a steep decline in Gleevec's effectiveness.

The new compound, AMN107, retains half the chemical composition of Gleevec while the other half of its makeup is designed to guarantee tighter binding to Bcr-Ab1. This increases the potency of AMN107 compared to Gleevec and potentially overcomes the resistance issues caused by Bcr-Abl mutations.

In one study, researchers at the Oregon Health and Science University compared the potency of AMN107 to Gleevec by testing cells expressing 16 different Gleevec-resistant, mutant versions of Bcr-Abl. They found that AMN107 was at least 20 times more potent than Gleevec against most of these mutations.

"Our findings show that 15 of the 16 mutants would be predicted to be sensitive to AMN107, while one mutant remains insensitive that would require a different, as yet undiscovered, inhibitor," research specialist Thomas O'Hare said in a prepared statement.

"These data indicate that AMN107 is a highly active Bcr-Abl inhibitor that may have clinical utility in patients with Gleevec-refractory CML," O'Hare said.

In related news, University of Texas M.D. Anderson Cancer Center researchers reported initial findings from an ongoing international study that found more than 70 percent of patients with advanced CML have shown a response to AMN107. Patients with early CML have shown a response rate of more than 90 percent.

The study is being funded by Novartis, which makes both AMN107 and Gleevec.

More information

The U.S. National Cancer Institute has more about CML treatment.

SOURCE: American Association for Cancer Research, news release, April 19, 2005
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