A phase I dose-escalation study of MSC1992371A, an oral inhibitor of aurora and other kinases, in advanced hematologic malignancies

A phase I dose-escalation study of MSC1992371A, an oral aurora kinase inhibitor, was carried out inpatients with hematologic malignancies. Patients received escalating doses either on days 1-3 and 8-10 (n = 36) or on days 1-6 (n = 39) of a 21-day cycle. The maximum tolerated doses were 37 and 28 mg/m(2)/day, respectively. Dose-limiting toxicities included severe neutropenia with infection and sepsis, mucositis/stomatitis, and diarrhea. Complete responses occurred in 3 patients. Four disease-specific expansion cohorts then received the dose and schedule dictated by the escalation phase but the study was prematurely discontinued due to hematologic and gastrointestinal toxicity at clinically effective doses. (C) 2013 Elsevier Ltd. All rights reserved.