Abstract
MK-0457, an Aurora kinase and BCR-ABL inhibitor, was studied on a Phase I/II study in 77 patients with refractory hematologic malignancies. The average number of cycles per patient was 3 (range 1-21). Maximum tolerated doses for a 5-day short infusion and continuous infusion regimens were 40 mg/m(2)/h and 144 mg/m(2)/h, respectively. Drug-related adverse events (AEs) included transient mucositis and alopecia. Eight of 18 patients with BCR-ABL T315I-mutated chronic myelogenous leukemia (44%) had hematologic responses and one of three patients (33%) with Philadelphia chromosome-positive acute lymphoblastic leukemia obtained complete remission. MK-0457 has important activity in patients with leukemias expressing the highly resistant T315I BCR-ABL mutation.
Publication types
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Clinical Trial, Phase I
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Clinical Trial, Phase II
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Aged
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Aged, 80 and over
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Aurora Kinases
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Drug Resistance, Neoplasm / drug effects
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Drug Resistance, Neoplasm / genetics
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Female
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Follow-Up Studies
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Fusion Proteins, bcr-abl / antagonists & inhibitors*
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Humans
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
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Leukemia, Myeloid, Acute / drug therapy*
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Leukemia, Myeloid, Acute / genetics
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Male
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Maximum Tolerated Dose
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Middle Aged
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Mutation / genetics*
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Neoplasm Staging
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Philadelphia Chromosome
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Piperazines / therapeutic use*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
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Prognosis
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Protein Kinase Inhibitors / therapeutic use*
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Remission Induction
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Young Adult
Substances
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Piperazines
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Protein Kinase Inhibitors
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tozasertib
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Fusion Proteins, bcr-abl
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Aurora Kinases
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Protein Serine-Threonine Kinases