A phase-1 study of dasatinib plus all-trans retinoic acid in acute myeloid leukemia.
Leuk Lymphoma
; 59(11): 2595-2601, 2018 11.
Article
em En
| MEDLINE
| ID: mdl-29616864
ABSTRACT
Src family kinases (SFKs) are hyperactivated in acute myeloid leukemia (AML). SFKs impede the retinoic acid receptor, and SFK inhibitors enhance all-trans retinoic acid (ATRA)-mediated cellular differentiation in AML cell lines and primary blasts. To translate these findings into the clinic, we undertook a phase-I dose-escalation study of the combination of the SFK inhibitor dasatinib and ATRA in patients with high-risk myeloid neoplasms. Nine subjects were enrolled six received 70 mg dasatinib plus 45 mg/m2 ATRA daily, and three received 100 mg dasatinib plus 45 mg/m2 ATRA daily for 28 days. Headache and QTc prolongations were the only two grade 3 adverse events observed. No significant clinical responses were observed. We conclude that the combination of 70 mg dasatinib and 45 mg/m2 ATRA daily is safe with acceptable toxicity. Our results provide the safety profile for further investigations into the clinical efficacy of this combination therapy in myeloid malignancies.
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MEDLINE
Assunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
/
Leucemia Mieloide
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article