Tosedostat Appears to Be Effective Leukemia Treatment

At 130 mg, is well tolerated and has substantial antileukemic activity

THURSDAY, Aug. 26 (HealthDay News) -- Tosedostat, a novel metalloenzyme inhibitor, appears to be well tolerated at 130 mg daily and to have a favorable risk-benefit profile for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome, according to research published online Aug. 23 in the Journal of Clinical Oncology.

Bob Löwenberg, M.D., of the Erasmus University Medical Center in Rotterdam, Netherlands, and colleagues conducted a phase I trial of 16 patients to define the maximum-tolerated dose of tosedostat and a phase II trial of 41 patients to evaluate the therapeutic effect of the maximum-acceptable dose of the drug in elderly and/or relapsing patients with myelodysplastic syndrome or AML.

The researchers found that three patients in the phase I trial, in which patients received 60 mg to 180 mg tosedostat for 28 days, reported dose-limiting toxicities. Patients in the phase II trial received 130 mg of the drug. Seven of the 51 AML patients in the study achieved complete marrow response, three of whom achieved complete remission; seven more achieved a partial marrow response, for an overall response rate of 27 percent. The most common severe adverse event was reduced platelet count.

"This phase I/II study demonstrates that oral once daily dosing with 130 mg tosedostat is well tolerated and has significant antileukemic activity. The favorable risk-benefit profile suggests that further clinical trials are warranted," the authors write.

Several authors disclosed financial relationships with Chroma Therapeutics, which supported the research.

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