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

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• 作者：Carlos Graux ; Anne Sonet ; Johan Maertens ; Justus Duyster ; Jochen Greiner ; Yves Chal ; on ; Giovanni Martinelli ; Dagmar Hess ; Dominik Heim ; Francis J. Giles ; Kevin R. Kelly ; Athos Gianella-Borradori ; Bl ; ine Longerey ; Ekaterine Asatiani ; Narmyn Rejeb ; Oliver G. Ottmann
• 关键词：Aurora kinase inhibitor ; MSC1992371A ; Phase l ; Hematologic malignancies
• 刊名：Leukemia Research
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：37
• 期：9
• 页码：1100-1106
• 全文大小：526 K

文摘

A phase I dose-escalation study of MSC1992371A, an oral aurora kinase inhibitor, was carried out in patients 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/m²/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.