{Reference Type}: Clinical Trial, Phase I
{Title}: A phase-1 study of dasatinib plus all-trans retinoic acid in acute myeloid leukemia.
{Author}: Redner RL;Beumer JH;Kropf P;Agha M;Boyiadzis M;Dorritie K;Farah R;Hou JZ;Im A;Lim SH;Raptis A;Sehgal A;Christner SM;Normolle D;Johnson DE;
{Journal}: Leuk Lymphoma
{Volume}: 59
{Issue}: 11
{Year}: 11 2018
暂无{DOI}: 10.1080/10428194.2018.1443330
{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.