ABSTRACT Dasatinib is an orally bioavailable potent inhibitor of multiple tyrosine kinases, including ABL and SRC. Preclinical studies have shown dasatinib to be a much more potent inhibitor of BCR-ABL than imatinib is, and to harbor efficacy against nearly all imatinib-resistant BCR-ABL mutants. Phase I clinical studies have been conducted in imatinib-resistant and -intolerant chronic myeloid leukemia and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia. No dose-limiting toxicity was observed at doses that harbored substantial clinical efficacy. Multinational phase II studies have confirmed the phase I experience and have led to accelerated approval by the U.S. Food and Drug Administration for the treatment of imatinib-resistant and -intolerant chronic myeloid leukemia as well as its full approval for the treatment of therapy-resistant Ph+ acute lymphoblastic leukemia.
- SourceAvailable from: ncbi.nlm.nih.govOchsner Journal 01/2007; 7(2):61-4.
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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.Expert Opinion on Pharmacotherapy 01/2008; 8(18):3257-64. DOI:10.1517/146565184.108.40.20657 · 3.09 Impact Factor