Dasatinib

General information

Dasatinib (BMS-354825), a thiazole carboximide derivative, is structurally related to imatinib. It targets src kinase and imatinib-resistant bcr–abl kinase and has impressive activity in patients with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia [ , ].

Although dasatinib has been approved for these indications in a dosage of 70 mg bd, the search for the optimal dose regimen continues [ ]. Preliminary data suggest that 100 mg/day may offer a more favorable benefit to harm balance in patients with chronic myeloid leukemia that is resistant to imatinib or in whom imatinib causes unacceptable adverse effects. Compared with conventional twice daily dosing, intermittent tyrosine kinase inhibition produces clinical remissions with improved safety, with the lowest incidence of pleural effusion (all grades), neutropenia (grades 3–4), and thrombocytopenia (grades 3–4). In addition, the use of dasatinib 100 mg/day makes dosage reductions less necessary than dosage schedules based on 50 mg bd [ ], 140 mg/day, or 70 mg bd. However, the accelerated phase or blast crisis makes doses of up to 100 mg bd necessary.

The main adverse effects of dasatinib include grade 3–4 hematological toxicity (for example neutropenia and thrombocytopenia), liver abnormalities, diarrhea, headache, peripheral edema, and hypocalcemia. In addition, pleural effusion is of clinical concern and may need treatment with diuretics and thoracentesis or pleurodesis.