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A phase I dose escalation study of oral bexarotene in combination with intravenous decitabine in patients with AML
Author(s) -
Welch John S.,
Niu Haixia,
Uy Geoffrey L.,
Westervelt Peter,
Abboud Camille N.,
Vij Ravi,
StockerlGoldstein Keith E.,
Jacoby Meagan,
Pusic Iskra,
Schroeder Mark A.,
Dipersio John F.,
Cashen Amanda F.
Publication year - 2014
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23735
Subject(s) - bexarotene , decitabine , medicine , myeloid leukemia , in vivo , oncology , retinoid x receptor , myeloid , pharmacology , retinoid , retinoic acid , chemistry , biology , nuclear receptor , gene expression , dna methylation , biochemistry , microbiology and biotechnology , transcription factor , gene
The response rate of non‐M3 acute myeloid leukemia (AML) to all trans retinoic acid has been limited. Using Affymetrix expression arrays, we found that in diverse AML blasts RXRA was expressed at higher levels than RARA and that mouse Ctsg‐PML‐RARA leukemia responded to bexarotene, a ligand for RXRA. We therefore performed a phase I study of combination bexarotene and decitabine in elderly and relapsed AML patients. We found that this combination was well tolerated, although outcomes were modest (1 CRi, and 3 PR among 19 patients). Correlative studies found that patients with clinical response had increased differentiation to bexarotene both in vivo and ex vivo, suggesting that pre‐treatment analysis might identify a more susceptible subgroup of patients. Am. J. Hematol. 89:E103–E108, 2014. © 2014 Wiley Periodicals, Inc.