Conflicts of Interest: The authors declare no relevant conflicts of interest.
A phase I dose escalation study of oral bexarotene in combination with intravenous decitabine in patients with AML
Article first published online: 28 APR 2014
© 2014 Wiley Periodicals, Inc.
American Journal of Hematology
Volume 89, Issue 8, pages E103–E108, August 2014
How to Cite
Welch, J. S., Niu, H., Uy, G. L., Westervelt, P., Abboud, C. N., Vij, R., Stockerl-Goldstein, K. E., Jacoby, M., Pusic, I., Schroeder, M. A., Dipersio, J. F. and Cashen, A. F. (2014), A phase I dose escalation study of oral bexarotene in combination with intravenous decitabine in patients with AML. Am. J. Hematol., 89: E103–E108. doi: 10.1002/ajh.23735
- Issue published online: 14 JUL 2014
- Article first published online: 28 APR 2014
- Accepted manuscript online: 10 APR 2014 04:47AM EST
- Manuscript Accepted: 7 APR 2014
- Manuscript Revised: 4 APR 2014
- Manuscript Received: 31 MAR 2014
- Eisai pharmaceuticals (IIS grant)
- NIH. Grant Numbers: K99/R00 HL103975-03, P50 CA171963-01A1 (PI: DC Link; Project 1 Co-Leader)
- NCI Cancer Center Support Grant (the Siteman Cancer Center). Grant Number: #P30 CA91842
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.