Yazarlar : Wang ES, Yee K, Koh LP, Hogge D, Enschede S, Carlson DM, Dudley M, Glaser K, McKeegan E, Albert DH, Li X, Pradhan R, Stock W.

Yayın : Leuk Lymphoma.

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/22280537

Konu : Lösemi

Literatür İçeriği :  

Abstract

Abstract Linifanib, a potent oral inhibitor of fms-like tyrosine kinase 3 (FLT3) and vascular endothelial growth factor receptor tyrosine kinases, has demonstrated promising preclinical single-agent and synergistic anti-leukemic activity in combination with cytarabine. In this phase-1, multi-center, open-label, dose-escalation study, 45 adults with relapsed/refractory acute myeloid leukemia (AML) received linifanib alone in Arm A (n=29) and linifanib plus intermediate-dose cytarabine in Arm B (n=16). Median treatment duration was 21 days (range 5-110). Linifanib was well tolerated overall. The most common Grade 3/4 events were fatigue (Arm A) and febrile neutropenia (Arm B). The recommended phase-2 dose was 15 mg (alone), and 10 mg (with cytarabine). Evidence of on-target kinase inhibition in FLT3-mutant and wild-type AML patients was seen. Decreased phosphorylated FLT3 was seen in 3/3 FLT3-ITD patients with peripheral blast reductions and in 8/24 (33%) patients with wild-type, D835, or unknown FLT3 mutation. Eight/29 (28%) patients had decreased phosphorylated ERK.

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