Assuntos
Ciclopentanos/efeitos adversos , Inibidores Enzimáticos/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Pirimidinas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclopentanos/administração & dosagem , Inibidores Enzimáticos/administração & dosagem , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Proteína NEDD8/antagonistas & inibidores , Pirimidinas/administração & dosagem , Adulto JovemRESUMO
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.