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The Food and Drug Administration has approved the use of Bosulif (bosutinib) to treat patients with chronic, accelerated, or blast-phase Philadelphia chromosome-positive chronic myelogenous leukemia (CML) who are resistant to or cannot tolerate other therapies, including imatinib.


Bosulif is a kinase inhibitor that limits cancer cell growth by inhibiting the Abl and Src signaling pathways.


"With the approval of tyrosine kinase inhibitors, we are seeing improvements in the treatment of CML based on a better understanding of the molecular basis of the disease," said Richard Pazdur, MD, Director of the FDA's Office of Hematology and Oncology Products. "These improvements have been observed in chronic and accelerated phases of CML."


This approval follows the previously approved drugs for CML-imatinib, approved in 2001, dasatinib in 2006, and nilotinib in 2007.


The safety and effectiveness of Bosulif, made by Pfizer, were evaluated in a single clinical trial of 546 adults with chronic, accelerated, or blast-phase CML. All patients had disease that had progressed after treatment with imatinib or imatinib followed by dasatinib and/or nilotinib, or who could not tolerate the side effects of previous treatment.


In patients with chronic-phase CML, efficacy was determined by the number of patients who had a major cytogenetic response (MCyR) within the first 24 weeks of treatment. A total of 34 percent of patients who had been previously treated with imatinib achieved a MCyR after 24 weeks. Of the patients who had an MCyR at any time, about 53 percent had a response that lasted for at least 18 months.

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Among patients previously treated with imatinib followed by dasatinib and/or nilotinib, about 27 percent achieved an MCyR within the first 24 weeks of treatment. Of those who achieved MCyR at any time, about 51 percent had their the MCyR last at least nine months.


In patients with accelerated CML previously treated with at least imatinib, 33 percent had their blood counts return to a normal range (i.e., a complete hematologic response) and 55 percent had normal blood counts with no evidence of leukemia (overall hematologic response) within the first 48 weeks of treatment. Meanwhile, 15 and 28 percent of patients with blast-phase CML achieved a complete hematologic response and an overall hematologic response, respectively.


"Bosulif is an important new addition to the CML treatment landscape," said Jorge E. Cortes, MD, a lead investigator of the Pfizer-sponsored registration study and Deputy Chair and Professor of Medicine in the Department of Leukemia at the University of Texas MD Anderson Cancer Center. "Despite recent advances, an unmet need remains for many CML patients who are refractory to one or more tyrosine kinase inhibitors."


The most common side effects observed in patients receiving Bosulif were diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, fever, and fatigue.


The recommended dose, a news release notes, is 500 mg, orally, taken once daily, with food.