On June 28, 2006, the U.S. Food and Drug Administration approved dasatinib (Sprycel; Bristol-Myers Squibb), a new small-molecule inhibitor of multiple tyrosine kinases, for the treatment of adults with chronic phase, accelerated phase, or myeloid or lymphoid blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) with resistance or intolerance to prior therapy including imatinib. The approval was based on four single-arm multicenter studies that combined 445 patietns and supported the efficacy and safety of dasatinib.
The FDA approval was for newly diagnosed patients; however, there is evidence that Sprycel is effective in patients who fail imatinib as well. Study CALGB 180-034 was designed to assess the efficacy and safety of dasatinib following intolerance or resistance to imatinib. With six years fo followup, thirty-one percent of patients randomised to receive dasatinib 100 mg once daily remained on treatment.
In patients with chronic phase CML, the six-year data shows progression-free survival of 49.3% and an overall survival of 71% for patients randomised to dasatinib 100 mg once daily (n=167), with 6% of patients (n=10) progressing to accelerated or blast phase on study at six years of follow-up. The primary efficacy end point in chronic phase CML was major cytogenetic response. Common toxicities with dasatinib included myelosuppression, bleeding, and fluid retention.
Sprycel is FDA indicted for first line, and for second line, it is supported by the CALGB-180-34 results.
nccn, CML 2014
Brave M, Goodman V, Kaminskas E, Farrell A, Timmer W, Pope S, Harapanhalli R, Saber H, Morse D, Bullock J, Men A, Noory C, Ramchandani R, Kenna L, Booth B, Gobburu J, Jiang X, Sridhara R, Justice R, Pazdur R.Sprycel for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to or intolerant of imatinib mesylate. Clin Cancer Res. 2008 Jan 15;14(2):352-9.
Shah, N., et al. Six-year follow-up of patients with imatinib-resistant
or -intolerant chronic-phase chronic myeloid leukemia (CML-CP) receiving dasatinib. Oral Presentation at: 2012 American Society of Clinical Oncology Annual Meeting. 3.Macmillan Cancer Support. Leukaemia Overview. Available at: http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Leukaemia/Leukaemiaoverview.aspx
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