MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia.

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.

• Authors: F J Giles, R T Swords, A Nagler, A Hochhaus, O G Ottmann, D A Rizzieri, M Talpaz, J Clark, P Watson, A Xiao, B Zhao, D Bergstrom, P D Le Coutre, S J Freedman, J E Cortes
• Journal: Leukemia (Leukemia) Vol. 27 Issue 1 Pg. 113-7 (Jan 2013) ISSN: 1476-5551 [Electronic] England
• PMID: 22772060 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Piperazines
• Protein Kinase Inhibitors
• tozasertib
• Fusion Proteins, bcr-abl
• Aurora Kinases
• Protein Serine-Threonine Kinases

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Aurora Kinases
• Drug Resistance, Neoplasm (drug effects, genetics)
• Female
• Follow-Up Studies
• Fusion Proteins, bcr-abl (antagonists & inhibitors)
• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, genetics)
• Leukemia, Myeloid, Acute (drug therapy, genetics)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Mutation (genetics)
• Neoplasm Staging
• Philadelphia Chromosome
• Piperazines (therapeutic use)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, genetics)
• Prognosis
• Protein Kinase Inhibitors (therapeutic use)
• Protein Serine-Threonine Kinases (antagonists & inhibitors)
• Remission Induction
• Young Adult