title: A phase I dose-escalation study of MSC1992371A, an oral inhibitor of aurora and other kinases, in advanced hematologic malignancies.
abstract: 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/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.
authors.affiliation: Mont-Godinne University Hospital (UCL), Yvoir, Belgium. carlos.graux@uclouvain.be
authors.forename: Carlos
authors.initials: C
authors.lastname: Graux
authors.forename: Anne
authors.initials: A
authors.lastname: Sonet
authors.forename: Johan
authors.initials: J
authors.lastname: Maertens
authors.forename: Justus
authors.initials: J
authors.lastname: Duyster
authors.forename: Jochen
authors.initials: J
authors.lastname: Greiner
authors.forename: Yves
authors.initials: Y
authors.lastname: Chalandon
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Dagmar
authors.initials: D
authors.lastname: Hess
authors.forename: Dominik
authors.initials: D
authors.lastname: Heim
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Kelly
authors.forename: Athos
authors.initials: A
authors.lastname: Gianella-Borradori
authors.forename: Blandine
authors.initials: B
authors.lastname: Longerey
authors.forename: Ekaterine
authors.initials: E
authors.lastname: Asatiani
authors.forename: Narmyn
authors.initials: N
authors.lastname: Rejeb
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Ottmann
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012074:Remission Induction; D014018:Tissue Distribution
chemical_list: D047428:Protein Kinase Inhibitors
keywords: Aurora kinase inhibitor; Hematologic malignancies; MSC1992371A; Phase l