Dasatinib for the treatment of Philadelphia chromosome-positive chronic myelogenous leukaemia after imatinib failure

Abstract

Dasatinib, a potent, oral kinase inhibitor, is presently approved for Philadelphia-positive chronic myelogenous leukaemia (CML) following imatinib failure. In an in vitro study, dasatinib had 325-fold greater potency than imatinib for inhibiting unmutated BCR-ABL. Phase I and II data show that dasatinib 70 mg b.i.d. is effective after imatinib failure in various phases of CML. Comparative data of dasatinib versus high-dose imatinib in patients with resistance or intolerance to imatinib demonstrated that dasatinib was associated with improved response rates and progression-free survival. Side effects of dasatinib, including pleural effusions, are manageable with modification of dose or schedule. Phase III dose optimisation studies and future indications are also discussed.