A phase-1 study of dasatinib plus all-trans retinoic acid in acute myeloid leukemia.

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 dasa

SUBMITTER: Redner RL 

PROVIDER: S-EPMC6201295 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature