signature=b3d79d176c8d30ce9c6503d7253fab5b,Dasatinib

摘要：

Dasatinib is an orally available short-acting dual ABL/SRC tyrosine kinase inhibitor (TKI). It potently inhibits BCR-ABL and SRC family kinases (SRC, LCK, YES, FYN), but also c-KIT, PDGFR-α and PDGFR-β, and ephrin receptor kinase. Dasatinib is an effective treatment for chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Both diseases are characterized by a constitutively active tyrosine kinase; BCR-ABL. Dasatinib inhibits BCR-ABL with greater potency compared with other BCR-ABL inhibitors and is active in CML resistant or intolerant to imatinib. Dasatinib is approved for the treatment of CML (all phases) and for the treatment of Ph+ ALL, resistant or intolerant to prior imatinib treatment. Randomized trial data in CML show that first-line dasatinib provides superior responses compared with imatinib and enables patients to achieve early, deep responses, correlated with improved longer-term outcomes. A once-daily dose of 100 mg in chronic phase CML results in high hematologic and molecular remission rates and prolongation of survival. In accelerated and blastic phase of CML, as well as in Ph+ ALL, complete hematologic and cytogenetic remissions frequently occur. Remissions however are very short. In these patients, once-daily 140 mg is the recommended dose. The effect of dasatinib in other malignancies including solid tumors is subject of clinical studies. Regardless of many clinical trials in different tumor types and in different combinations of dasatinib with other agents, the role of dasatinib in the treatment of solid tumors has not yet been defined. Side effects of dasatinib are frequent but mostly moderate and manageable and include cytopenias and pleural effusions. The review presents the preclinical and clinical activity of dasatinib with a focus on clinical studies in CML.

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