Dasatinib dosing strategies in Philadelphia chromosome-positive leukemia

Abstract

Introduction. Imatinib resistance has emerged as a significant clinical issue in the treatment of chronic myelogenous leukemia (CML) and Philadelphia chromosome positive acute lymphocytic leukemia (Ph+ ALL). Imatinib intolerance is also a concern. Dasatinib is approved for the treatment of patients with imatinib-resistant or -intolerant CML or Ph+ ALL and has helped address these concerns. Here, we review the clinical profile of dasatinib and discuss dosing strategies to manage these adverse events. Methods. References were obtained through literature searches on PubMed as well as from the Proceedings of Annual Meetings of the American Society of Clinical Oncology, the American Society of Hematology, and European Hematology Association. Results. Initial studies of dasatinib showed that 70 mg twice-daily resulted in impressive hematologic and cytogenetic responses in patients with all phases of CML and Ph+ ALL. Aside from hematologic events, the most common drug-related toxicities (mostly grade 1—2) in dasatinib clinical trials were fluid retention (including pleural effusion), diarrhea, skin rash, headache, hemorrhage, fatigue, nausea and dyspnea. A Phase III dose optimization study showed that the safety profile of dasatinib is improved and efficacy maintained when administered on a 100 mg once-daily dosing schedule compared with the 70 mg twice-daily schedule in patients with chronic phase (CP) CML. Conclusion. The safety profile of dasatinib is manageable. A 100 mg once-daily dose is now approved for use in patients with CP CML. A dose of 70 mg twice daily remains the recommended dosage for use in patients with advanced phase CML or Ph+ ALL. J Oncol Pharm Practice (2009) 15: 17—27.