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Dasatinib

  • Markus Lindauer
  • Andreas Hochhaus
Chapter
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 212)

Abstract

Dasatinib is an oral available short-acting inhibitor of multiple tyrosine kinases. It was designed to inhibit ABL and SRC, but also has activity in multiple other kinases, including c-KIT, PDGFR-α, PDGFR-β, and ephrin receptor kinases. Dasatinib is a very potent inhibitor of BCR-ABL and an effective treatment for the BCR-ABL-driven diseases chronic myeloid leukemia (CML) and Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), characterized by the constitutively active tyrosine kinase, BCR-ABL. Dasatinib is approved for the treatment of CML (all phases) including children and for the treatment of Ph+ ALL, resistant or intolerant to prior imatinib treatment. Randomized trials in CML comparing dasatinib with imatinib show that first-line dasatinib causes significantly deeper and faster molecular remissions. In accelerated and blastic phase CML, as well as in Ph+ ALL, dasatinib frequently induces complete hematologic and cytogenetic remissions even in imatinib pretreated patients. Remissions however are often short. Dasatinib is administered independent of food intake as a once-daily dose of 100 mg in chronic phase CML and 140 mg in Ph+ ALL or blastic phase. 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.

Keyword

Chronic myeloid leukemia Tyrosine kinase inhibitor Dasatinib 

Abbreviations

ALL

Acute lymphoblastic leukemia

AML

Acute myeloid leukemia

AP

Accelerated phase

BID

Twice daily

BP

Blast phase

CCyC

Complete cytogenetic response

CEL

Chronic eosinophilic leukemia

CHR

Complete hematologic response

CLL

Chronic lymphocytic leukemia

CML

Chronic myeloid leukemia

CMML

Chronic myelomonocytic leukemia

CP

Chronic phase

CR

Complete response

CRI

Complete response with incomplete hematologic recovery

CRPC

Castration-resistant prostate cancer

HES

Hypereosinophilic syndrome

MDS

Myelodysplastic syndrome

MMR

Major molecular response

OS

Overall survival

PFS

Progression-free survival

Ph+

Philadelphia chromosome positive

PMF

Primary myelofibrosis

PR

Partial remission

QD

Daily

SD

Stable disease

SM

Systemic mastocytosis

TKI

Tyrosine kinase inhibitor

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Klinik für Innere Medizin IIIKlinikum am GesundbrunnenHeilbronnGermany
  2. 2.Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin IIUniversitätsklinikum JenaJenaGermany

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