Subject(s)
Cyclopentanes/adverse effects , Enzyme Inhibitors/adverse effects , Leukemia, Myeloid, Acute/drug therapy , Myelodysplastic Syndromes/drug therapy , Pyrimidines/adverse effects , Adult , Aged , Aged, 80 and over , Cyclopentanes/administration & dosage , Enzyme Inhibitors/administration & dosage , Female , Humans , Male , Maximum Tolerated Dose , Middle Aged , NEDD8 Protein/antagonists & inhibitors , Pyrimidines/administration & dosage , Young AdultABSTRACT
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.
