%0 Clinical Trial, Phase I
%T A phase-1 study of dasatinib plus all-trans retinoic acid in acute myeloid leukemia.
%A Redner RL
%A Beumer JH
%A Kropf P
%A Agha M
%A Boyiadzis M
%A Dorritie K
%A Farah R
%A Hou JZ
%A Im A
%A Lim SH
%A Raptis A
%A Sehgal A
%A Christner SM
%A Normolle D
%A Johnson DE
%J Leuk Lymphoma
%V 59
%N 11
%D 11 2018
%M 29616864
暂无%R 10.1080/10428194.2018.1443330
%X 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.