Dasatinib: in chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia

BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
Susan J Keam

Abstract

Dasatinib is a small-molecule inhibitor of multiple tyrosine kinases, including BCR-ABL, SRC, c-KIT, ephrin A receptor and platelet-derived growth factor-beta receptor kinases, at nanomolar concentrations. In vitro, dasatinib is 325-fold more potent than imatinib against cells expressing wild-type BCR-ABL. The efficacy and tolerability of oral dasatinib has been established in the START phase II trials in adults with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) who were intolerant or resistant to imatinib, and optimal dasatinib dosage regimens were identified in phase III randomized trials. In patients with chronic phase CML, the major cytogenetic response rate in the START-C trial (median follow-up 15.2 months) was 59% with dasatinib, and in the randomized START-R trial (median follow-up 15 months), was greater with dasatinib than with high-dose imatinib (52% vs 33%). Major hematologic response rates with dasatinib were 63% in patients with accelerated phase CML (follow-up > or =9 months; START-A trial), 34% in patients with myeloid blast phase CML and 35% in those with lymphoid blast phase CML (follow-up > or =12 months; START-B and START-L trials), and 41% ...Continue Reading

Citations

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