Dasatinib (BMS-354825, Sprycel®) is an oral, multitargeted inhibitor of
receptor tyrosine kinases (RTKs), including
BCR-ABL fusion protein,
stem cell factor receptor (c-KIT),
platelet-derived growth factor receptor (PDGFR), and
Src family kinases (SFKs). Several early- and late-phase clinical trials for chronic myelogeneous leukaemia (CML) have demonstrated the direct inhibition of
BCR-ABL fusion protein and SFKs, which led to
dasatinib approval by the Food and Drug Administration (FDA) and the European Union for the treatment of
imatinib-resistant or -intolerant CML, and
Philadelphia chromosome-positive
acute lymphoblastic leukemia (Ph+ ALL). Phase III dose-optimization study was performed to compare different regimens, stating that
dasatinib 100 mg once daily is now the recommended schedule for patients with chronic CML, and 140 mg once daily for patients with accelerated phase or myeloid or lymphoid
blast phase CML, and for patients with Ph+ ALL until progression. Because of the myriad of critical roles of SFKs in biological processes, SFKs inhibition could induce numerous
biological responses. Ongoing clinical trials evaluate
dasatinib in the treatment of several solid tumours, including gastrointestinal stromal tumours (GIST),
prostate cancer,
malignant pleural mesothelioma,
sarcomas, NSCLC,
colorectal cancer,
glioblastoma and other haematologic
malignancies as
multiple myeloma. Ongoing pre-clinical studies assess the therapeutic potential of
dasatinib in other solid tumours, including
melanoma,
head and neck cancer,
breast cancer and
ovarian cancer.
Dasatinib is generally well tolerated. Myelosuppression is the common adverse event which is, however, reversible by
dose reduction, discontinuation, or interruption.
Thrombocytopenia is more significant than
neutropenia and associated to gastrointestinal
bleeding and CNS haemorrhage. The most common non-haematologic adverse events include gastrointestinal symptoms (diarrhoea,
nausea,
vomiting,
abdominal pain and
anorexia),
headache, peripheral
edema, and
pleural effusion. In respect of these encouraging studies investigating
dasatinib in the treatment of patients with GIST,
prostate cancer,
multiple myeloma and
sarcomas, ongoing phase III clinical trials warrant the
drug evaluation as recommended agent for the treatment of these diseases, also in association with
chemotherapy or other targeted
therapies.