Dasatinib Effective Against Difficult-to-Treat Acute Lymphoblastic Leukemia Adapted from the NCI Cancer Bulletin, vol. 4/no.18, May 29, 2007 (see the current issue).
The results of a 36-patient phase II clinical trial indicate that the the multitargeted drug dasatinib (Sprycel ™) may be extremely beneficial in adult patients with a form of acute lymphoblastic leukemia (ALL) who have developed resistance or do not respond to another targeted agent, imatinib mesylate (Gleevec®). The drug's effectiveness did not appear to be hampered by most of the mutations in a key protein that have been associated with imatinib resistance.
Patients in the trial had a specific chromosomal translocation, often referred to as the Philadelphia chromosome, that is associated with a rapid course of disease after ALL diagnosis and poor survival. The translocation creates a fused protein known as BCR-ABL, the same protein typically seen in chronic myelogenous leukemia, for which imatinib has proven to be an effective treatment.
"These data are highly significant given the refractory nature of patients enrolled in this trial to current treatment modalities, including imatinib," wrote study leader Dr. Olivier Ottmann from Johann Wolfgang Goethe University in Germany and colleagues in a May 11 early online release in Blood.
In the study, patients given dasatinib at 70 mg twice daily had strong hematologic and cytogenetic response rates - meaning a return of normal white blood cell counts and a significantly reduced number of cells positive for the Philadelphia chromosome, respectively. At 8 months, 42 percent of patients had a major hematologic response, of whom two-thirds exhibited no disease progression; 58 percent of patients had complete cytogenetic responses.
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