Dasatinib (Sprycel®) is an orally administered small molecule inhibitor of multiple
tyrosine kinases, including BCR-ABL and
SRC family kinases, which is indicated for the treatment of adults with newly diagnosed chronic-phase chronic myeloid leukaemia (CML), CML (chronic-, accelerated- or
blast-phase) with resistance or intolerance to prior
therapy, including
imatinib, or
Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) with resistance or intolerance to prior
therapy.
Dasatinib is ≈325-fold more active than
imatinib in inhibiting wild-type ABL
kinase in vitro and is active against a wide variety of
imatinib-resistant BCR-ABL mutants, except for T315I. This article reviews the efficacy and tolerability of
dasatinib in the treatment of patients with newly diagnosed chronic-phase CML or
imatinib-resistant or -intolerant CML or Ph+ ALL, as well as summarizing its pharmacological properties. In clinical trials, oral
dasatinib was effective in achieving major or complete cytogenetic responses in both newly diagnosed and
imatinib-resistant or -intolerant chronic-phase CML.
Dasatinib was likewise effective in achieving major or overall haematological responses in
imatinib-resistant or -intolerant, accelerated- or
blast-phase CML, or Ph+ ALL. Responses were rapidly achieved within 1-3 months and were durable over 1-5 years of follow-up. The majority of adverse events with
dasatinib were of mild to moderate severity. Fluid retention (including
pleural effusion) was the most common adverse event. Haematological abnormalities were common and
cytopenias were the most common grade 3/4 adverse events.
Dasatinib 100 mg administered once daily was as effective as
dasatinib 70 mg administered twice daily, and was better tolerated, being associated with lower incidences of
pleural effusion and grade 3/4
thrombocytopenia, in particular.
Dasatinib was more effective than high-dose
imatinib in the treatment of patients with
imatinib-resistant chronic-phase CML and was more effective than standard dosages of
imatinib, as well as being associated with less frequent fluid retention, in patients with newly diagnosed chronic-phase CML.
Dasatinib was generally equally effective in patients with or without BCR-ABL mutations at baseline. Therefore, oral
dasatinib is a highly effective once-daily
therapy for the first-line treatment of newly diagnosed patients with chronic-phase CML, as well as for the treatment of patients with
imatinib-resistant or -intolerant chronic- and advanced-phase CML or Ph+ ALL.