Investigational Aurora A kinase inhibitor alisertib (MLN8237) as an enteric-coated tablet formulation in non-hematologic malignancies: Phase 1 dose-escalation study
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چکیده
منابع مشابه
An exploratory phase 2 study of investigational Aurora A kinase inhibitor alisertib (MLN8237) in acute myelogenous leukemia and myelodysplastic syndromes
Alisertib (MLN8237) is an investigational, oral, selective, Aurora A kinase (AAK) inhibitor. In this phase 2 trial, 57 patients with acute myeloid leukemia (AML) or high-grade myelodysplastic syndrome received alisertib 50 mg BID for 7 days in 21-day cycles. Responses in 6/35 AML patients (17% response rate with an additional 49% stable disease, 34% transfusion independence) included 1 complete...
متن کاملCharacterization of Alisertib (MLN8237), an investigational small-molecule inhibitor of aurora A kinase using novel in vivo pharmacodynamic assays.
PURPOSE Small-molecule inhibitors of Aurora A (AAK) and B (ABK) kinases, which play important roles in mitosis, are currently being pursued in oncology clinical trials. We developed three novel assays to quantitatively measure biomarkers of AAK inhibition in vivo. Here, we describe preclinical characterization of alisertib (MLN8237), a selective AAK inhibitor, incorporating these novel pharmaco...
متن کاملA 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 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 seps...
متن کاملPhase I study of aurora A kinase inhibitor MLN8237 in advanced solid tumors: safety, pharmacokinetics, pharmacodynamics, and bioavailability of two oral formulations.
PURPOSE This phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of the investigational oral drug MLN8237 (alisertib), a small-molecule Aurora A kinase (AAK) inhibitor, in 87 adult patients with advanced solid tumors. EXPERIMENTAL DESIGN Sequential cohorts of patients received MLN8237 5 to 150 mg orally once daily or twice daily for 7, 14, or 21 days, followed...
متن کاملTranslational exposure-efficacy modeling to optimize the dose and schedule of taxanes combined with the investigational Aurora A kinase inhibitor MLN8237 (alisertib).
Aurora A kinase orchestrates multiple key activities, allowing cells to transit successfully into and through mitosis. MLN8237 (alisertib) is a selective Aurora A inhibitor that is being evaluated as an anticancer agent in multiple solid tumors and heme-lymphatic malignancies. The antitumor activity of MLN8237 when combined with docetaxel or paclitaxel was evaluated in in vivo models of triple-...
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ژورنال
عنوان ژورنال: Investigational New Drugs
سال: 2014
ISSN: 0167-6997,1573-0646
DOI: 10.1007/s10637-014-0121-6