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. 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.
Division of Oncology, Department of Internal Medicine, Washington University, St Louis, Missouri.
John S
JS
Welch
Haixia
H
Niu
Geoffrey L
GL
Uy
Peter
P
Westervelt
Camille N
CN
Abboud
Ravi
R
Vij
Keith E
KE
Stockerl-Goldstein
Meagan
M
Jacoby
Iskra
I
Pusic
Mark A
MA
Schroeder
John F
JF
Dipersio
Amanda F
AF
Cashen
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077610:Bexarotene; D000077209:Decitabine; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007275:Injections, Intravenous; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D000072482:Retinoic Acid Receptor alpha; D047490:Retinoid X Receptor alpha / Q000235:genetics / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D000964:Antimetabolites, Antineoplastic; C000607071:RARA protein, human; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047490:Retinoid X Receptor alpha; D013764:Tetrahydronaphthalenes; D000077209:Decitabine; D000077610:Bexarotene; D001374:Azacitidine