NDLI: The mTOR inhibitor everolimus in combination with azacitidine in patients with relapsed/refractory acute myeloid leukemia: a phase Ib/II study.

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The mTOR inhibitor everolimus in combination with azacitidine in patients with relapsed/refractory acute myeloid leukemia: a phase Ib/II study.

Content Provider	Europe PMC
Author	Tan, Peter Tiong, Ing Soo Fleming, Shaun Pomilio, Giovanna Cummings, Nik Droogleever, Mark McManus, Julie Schwarer, Anthony Catalano, John Patil, Sushrut Avery, Sharon Spencer, Andrew Wei, Andrew
Copyright Year	2017
Abstract	Therapeutic options are limited in relapsed/refractory acute myeloid leukemia (AML). We evaluated the maximum tolerated dose (MTD) and preliminary efficacy of mammalian target of rapamycin (mTOR) inhibitor, everolimus (days 5–21) in combination with azacitidine 75 mg/m2 subcutaneously (days 1–5 and 8–9 every 28 days) in 40 patients with relapsed (n = 27), primary refractory (n = 11) or elderly patients unfit for intensive chemotherapy (n = 2). MTD was not reached following everolimus dose escalation (2.5, 5 or 10 mg; n = 19) to the 10 mg dose level which was expanded (n = 21). Major adverse events (grade > 2) were mostly disease-related: neutropenia (73%), thrombocytopenia (67%), mucositis (24%) and febrile neutropenia (19%). Overall survival (OS) of the entire cohort was 8.5 months, and overall response rate (ORR; including CR/CRi/PR/MLFS) was 22.5%. Furthermore, a landmark analysis beyond cycle 1 revealed superior OS and ORR in patients receiving 2.5 mg everolimus with azoles, compared to those without azoles (median OS 12.8 vs. 6.0 months, P = 0.049, and ORR 50% vs. 16%, P = 0.056), potentially due to achievement of higher everolimus blood levels. This study demonstrates that everolimus in combination with azacitidine is tolerable, with promising clinical activity in advanced AML.
Journal	Oncotarget
Volume Number	8
PubMed Central reference number	PMC5581027
Issue Number	32
PubMed reference number	28881728
e-ISSN	19492553
DOI	10.18632/oncotarget.13699
Language	English
Publisher	Impact Journals LLC
Publisher Date	2016-11-29
Access Restriction	Open
Rights License	This article is distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. Copyright: © 2017 Tan et al.
Subject Keyword	acute myeloid leukemia everolimus azacitidine mTOR clinical trial
Content Type	Text
Resource Type	Article
Subject	Oncology

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