A phase I dose escalation study of oral bexarotene in combination with intravenous decitabine in patients with AML

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...

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Bibliographic Details
Published in:American journal of hematology 2014-08, Vol.89 (8), p.E103-E108
Main Authors: Welch, John S., Niu, Haixia, Uy, Geoffrey L., Westervelt, Peter, Abboud, Camille N., Vij, Ravi, Stockerl‐Goldstein, Keith E., Jacoby, Meagan, Pusic, Iskra, Schroeder, Mark A., Dipersio, John F., Cashen, Amanda F.
Format: Article
Language:English
Subjects:
Administration, Oral
Aged
Aged, 80 and over
Animals
Anticarcinogenic Agents - therapeutic use
Antimetabolites, Antineoplastic - therapeutic use
Azacitidine - analogs & derivatives
Azacitidine - therapeutic use
Bexarotene
Decitabine
Drug Administration Schedule
Drug Therapy, Combination
Female
Gene Expression
Gene Expression Profiling
Hematology
Humans
Injections, Intravenous
Leukemia, Promyelocytic, Acute - drug therapy
Leukemia, Promyelocytic, Acute - genetics
Leukemia, Promyelocytic, Acute - metabolism
Leukemia, Promyelocytic, Acute - pathology
Male
Mice
Middle Aged
Receptors, Retinoic Acid - genetics
Receptors, Retinoic Acid - metabolism
Recurrence
Retinoic Acid Receptor alpha
Retinoid X Receptor alpha - genetics
Retinoid X Receptor alpha - metabolism
Tetrahydronaphthalenes - therapeutic use
Tumor Cells, Cultured
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Summary: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.
ISSN:0361-8609
1096-8652
1096-8652
DOI:10.1002/ajh.23735