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AMN107 has potent activity in leukemia resistant to Gleevec

The targeted agent AMN107 can produce dramatic benefits in patients with some forms of leukemia that are resistant to Gleevec, the standard therapy for these cancers, say researchers at The University of Texas M. D. Anderson Cancer Center (meeting abstract #37).

At the 47th Annual Meeting of the American Society of Hematology (ASH), the investigators reported marked improvement in outcome in all three phases of chronic myeloid leukemia (CML) as well as benefit in treating a form of acute lymphocytic leukemia (ALL) that shares the same genetic abnormality as CML, the Philadelphia chromosome.

"This drug is very promising and appears at this point to offer an effective option for patients who do not achieve an optimal response to Gleevec therapy," says Hagop Kantarjian, M.D., professor and chair of the Department of Leukemia.

If additional studies continue to show such results, Kantarjian says, he believes AMN107, which is taken in pill form, "will either replace Gleevec as the standard of care in the future or will be used in combination with it."

Both CML and Philadelphia-positive ALL is caused by the swapping of genetic material in bone marrow stem cells between two chromosomes, which produces an abnormality called the Philadelphia chromosome. This new gene then produces a novel tyrosine kinase (Bcr-Abl) that signals the abnormal cell growth that leads to development of leukemia.

While both Gleevec and AMN107 shut down the activity of Bcr-Abl, laboratory experiments with AMN107 show it is up to 50 times more potent because it binds more efficiently to the enzyme than does Gleevec.

In the phase I clinical trial being reported, 119 patients who were resistant to Gleevec were given AMN107, and in some cases the dose was increased up to twelve fold. The researchers found that the range of response varied, depending on the form of the cancer and the presence of genetic mutations. For example, hematologic response fr
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Contact: Nancy Jensen
nwjensen@mdanderson.org
713-794-1584
University of Texas M. D. Anderson Cancer Center
10-Dec-2005


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