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

作者：Graux Carlos^*; Sonet Anne; Maertens Johan; Duyster Justus; Greiner Jochen; Chalandon Yves; Martinelli Giovanni; Hess Dagmar; Heim Dominik; Giles Francis J; Kelly Kevin R; Gianella Borradori Athos; Longerey Blandine; Asatiani Ekaterine; Rejeb Narmyn; Ottmann Oliver G

来源：Leukemia Research, 2013, 37(9): 1100-1106.

DOI：10.1016/j.leukres.2013.04.025

• Aurora kinase inhibitor
• MSC1992371A
• Phase l
• 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.

• 出版日期2013-9