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Dasatinib

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Small Molecules in Hematology

Part of the book series: Recent Results in Cancer Research ((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.

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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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  1. Klinik für Innere Medizin III, Klinikum am Gesundbrunnen, Am Gesundbrunnen 20–24, 74078, Heilbronn, Germany

    Markus Lindauer

  2. Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Erlanger Allee 101, 07740, Jena, Germany

    Andreas Hochhaus

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    Uwe M. Martens

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Lindauer, M., Hochhaus, A. (2018). Dasatinib. In: Martens, U. (eds) Small Molecules in Hematology. Recent Results in Cancer Research, vol 212. Springer, Cham. https://doi.org/10.1007/978-3-319-91439-8_2

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