RESUMO
MGCD0103 is an isotype-selective inhibitor of histone deacetylases (HDACs) targeted to isoforms 1, 2, 3, and 11. In a phase 1 study in patients with leukemia or myelodysplastic syndromes (MDS), MGCD0103 was administered orally 3 times weekly without interruption. Twenty-nine patients with a median age of 62 years (range, 32-84 years) were enrolled at planned dose levels (20, 40, and 80 mg/m(2)). The majority of patients (76%) had acute myelogenous leukemia (AML). In all, 24 (83%) of 29 patients had received 1 or more prior chemotherapies (range, 0-5), and 18 (62%) of 29 patients had abnormal cytogenetics. The maximum tolerated dose was determined to be 60 mg/m(2), with dose-limiting toxicities (DLTs) of fatigue, nausea, vomiting, and diarrhea observed at higher doses. Three patients achieved a complete bone marrow response (blasts Assuntos
Benzamidas/administração & dosagem
, Benzamidas/farmacocinética
, Inibidores de Histona Desacetilases
, Leucemia/tratamento farmacológico
, Pirimidinas/administração & dosagem
, Pirimidinas/farmacocinética
, Administração Oral
, Adulto
, Idoso
, Idoso de 80 Anos ou mais
, Benzamidas/toxicidade
, Células Cultivadas
, Relação Dose-Resposta a Droga
, Feminino
, Histona Desacetilases/metabolismo
, Histonas/metabolismo
, Humanos
, Leucemia/complicações
, Leucemia Mieloide Aguda/complicações
, Leucemia Mieloide Aguda/tratamento farmacológico
, Masculino
, Dose Máxima Tolerável
, Pessoa de Meia-Idade
, Farmacocinética
, Pirimidinas/toxicidade