Translational Exposure–Efficacy Modeling to Optimize the Dose and Schedule of Taxanes Combined with the Investigational Aurora A Kinase Inhibitor MLN8237 (Alisertib)
نویسندگان
چکیده
منابع مشابه
Translational 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-...
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 کاملAn 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 کاملEffect of Food on the Pharmacokinetics of the Investigational Aurora A Kinase Inhibitor Alisertib (MLN8237) in Patients with Advanced Solid Tumors
OBJECTIVE This study was conducted to characterize the effects of food on single-dose pharmacokinetics (PK) of the investigational Aurora A kinase inhibitor alisertib (MLN8237) in patients with advanced solid tumors. METHODS Following overnight fasting for 10 h, a single 50 mg enteric-coated tablet (ECT) of alisertib was administered under either fasted (alisertib with 240 mL of water) or fed...
متن کاملScientific Rationale Supporting the Clinical Development Strategy for the Investigational Aurora A Kinase Inhibitor Alisertib in Cancer
Alisertib (MLN8237) is a selective small molecule inhibitor of Aurora A kinase that is being developed in multiple cancer indications as a single agent and in combination with other therapies. A significant amount of research has elucidated a role for Aurora A in orchestrating numerous activities of cells transiting through mitosis and has begun to shed light on potential non-mitotic roles for ...
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ژورنال
عنوان ژورنال: Molecular Cancer Therapeutics
سال: 2014
ISSN: 1535-7163,1538-8514
DOI: 10.1158/1535-7163.mct-14-0027