A Phase I and Pharmacodynamic Study of AT9283, a Small-Molecule Inhibitor of Aurora Kinases in Patients With Relapsed/Refractory Leukemia or Myelofibrosis

Micro-Abstract Aurora kinase (AK) inhibitors are active in a variety of leukemic models. A dose-escalation study of AK inhibitor AT9283 was performed in patients with relapsed or refractory leukemias. Dose-limiting toxicities included multiorgan failure, hypertension, and myocardial infarction. The...

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Bibliographic Details
Published in:Clinical lymphoma, myeloma and leukemia myeloma and leukemia, 2014-06, Vol.14 (3), p.223-230
Main Authors: Foran, James, Ravandi, Farhad, Wierda, William, Garcia-Manero, Guillermo, Verstovsek, Srdan, Kadia, Tapan, Burger, Jan, Yule, Murray, Langford, Gillian, Lyons, John, Ayrton, John, Lock, Victoria, Borthakur, Gautham, Cortes, Jorge, Kantarjian, Hagop
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Benzimidazoles - therapeutic use
Blood cancer
Clinical
Disease Progression
Dose escalation
Drug Administration Schedule
Female
Hematology, Oncology and Palliative Medicine
Humans
Leukemia - diagnosis
Leukemia - drug therapy
Leukemia - pathology
Male
Maximum Tolerated Dose
Middle Aged
Primary Myelofibrosis - diagnosis
Primary Myelofibrosis - drug therapy
Primary Myelofibrosis - pathology
Protein Kinase Inhibitors - pharmacology
Protein Kinase Inhibitors - therapeutic use
Recurrence
Response
Tolerability
Treatment Outcome
Urea - analogs & derivatives
Urea - therapeutic use
Young Adult
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Summary:Micro-Abstract Aurora kinase (AK) inhibitors are active in a variety of leukemic models. A dose-escalation study of AK inhibitor AT9283 was performed in patients with relapsed or refractory leukemias. Dose-limiting toxicities included multiorgan failure, hypertension, and myocardial infarction. The maximum tolerated dose was identified as 324 mg/m2 /72 h. Approximately one-third of patients with acute myeloid leukemia experienced significant reduction in bone marrow blasts; no durable responses were seen.
ISSN:2152-2650
2152-2669
DOI:10.1016/j.clml.2013.11.001