Posted on June 17th, 2011 by
Researchers involved in an international study have reported that a new tyrosine kinase inhibitor, bosutinib, appears to be superior to Gleevec® (imatinib) for the initial therapy of patients with chronic myeloid leukemia (CML). The early results of this randomized trial were presented at the 2011 meeting of the American Society of Clinical Oncology.
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. Bosutinib is said to be 30 times more potent than Gleevec and has been effective in the treatment of patients who have failed Gleevec and Sprycel or Gleevec and Tasigna. Bosutinib has also been effective in treating accelerated and blast phases of CML including patients who have failed stem cell transplantation. Targeting of Src by bosutinib is thought to be important as over-expression of Src kinases has been associated with resistance to Gleevec.
The current study randomly allocated 502 patients with newly diagnosed CML to treatment with Gleevec or bosutinib. These are early results (median of 16 months of treatment) and more follow-up will be needed for accurate comparison.
These data suggest that bosutinib may soon be added to approved drugs for the treatment of CML. The role of bosutinib as initial therapy will be defined with further follow-up of the current study.
Gambacorti-Passerini C, Cortes JE, Kim D, et al. Bosutinib (BOS) versus imatinib (IM) in patients (pts) with chronic phase chronic myeloid leukemia (CP CML) in the BELA trial: 18 month follow-up. Journal of Clinical Oncology 29;2011 (suppl;abstract 6509)
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