Posted on October 14th, 2011 by
Treatment with the investigational drug bosutinib produced promising rates of response among patients with chronic-phase chronic myeloid leukemia (CML) that had previously been treated with Gleevec® (imatinib). The results of this Phase I/II trial were published in Blood.
Each year in the United States, approximately 5,000 people are diagnosed with CML. Most cases of CML are characterized by a chromosomal abnormality—the Philadelphia chromosome—in which genetic material is exchanged between chromosome 9 and chromosome 22. This exchange brings together two genes: BCR and ABL. The combination of these two genes into the single BCR-ABL gene results in the production of a protein that contributes to uncontrolled cell growth.
Recognition of the pivotal role of the BCR-ABL protein in CML led to the development of Gleevec, which blocks the activity of this protein. Gleevec produced high rates of remission among patients with chronic-phase CML and dramatically changed the treatment of this disease. Newer drugs that target the BCR-ABL protein include Tasigna® (nilotinib) and Sprycel® (dasatinib). Both Tasigna and Sprycel appear to be superior to Gleevec for the initial treatment of patients with CML and are approved by the FDA for this purpose.
Bosutinib is a third-generation tyrosine kinase inhibitor that targets both Abl and Src kinases. Targeting of Src by bosutinib is thought to be important as over-expression of Src kinases has been associated with resistance to Gleevec.
To evaluate bosutinib among CML patients who were resistant to Gleevec or who could not tolerate Gleevec, researchers conducted a Phase I/II clinical trial among 288 patients. All had CML in chronic phase and all had previously been treated with Gleevec.
These results suggest that bosutinib may be effective and generally well tolerated for the treatment of chronic-phase CML that has previously been treated with Gleevec.
Reference: Cortes JE, Kantarjian HM, Brummendorf TH et al. Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive CML patients with resistance or intolerance to imatinib. Blood. Early online publication August 24, 2011.
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