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Report of a phase 1/2 study of a combination of azacitidine and cytarabine in acute myelogenous leukemia and high-risk myelodysplastic syndromes

2009; Taylor & Francis; Volume: 51; Issue: 1 Linguagem: Inglês

10.3109/10428190903318329

1042-8194

Gautam Borthakur, Xuelin Huang, Hagop M. Kantarjian, Stefan Faderl, Farhad Ravandi, Alessandra Ferrajoli, Ritva Torma, Gail Morris, Donald A. Berry, Jean‐Pierre J. Issa,

Acute Lymphoblastic Leukemia research

Cytarabine resistance characterizes relapsed and refractory acute myelogenous leukemia (AML). Restoration of cytarabine sensitivity can potentially improve treatment outcome in this setting. Acquired hypermethylation of gene promoters and associated silencing of gene expression has been implicated in chemo resistance, and drug-induced hypomethylation can improve sensitivity to cytarabine in vitro. We conducted an adaptively randomized study of a combination of azacitidine, a hypomethylating agent, and cytarabine in 34 patients with AML. The combination administered in a concomitant fashion is safe at full doses of azacitidine and cytarabine, without unexpected toxicities. However, in this advanced AML population, it was difficult to deliver more than one cycle of therapy, and minimal anti-leukemia activity was seen in patients with relapsed/refractory disease. Complete remission was achieved in 2 of 6 minimally pre-treated patients. We conclude that the combination of azacitidine and cytarabine is feasible but has limited activity in relapsed/refractory AML.