In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e18012-e18012
Abstract:
e18012 Background: Valproic acid (VPA, 2-propylpentanoic acid) is a histone deacetylase inhibitors (HDACi), which has in vitro activity against Acute Myeloid Leukemia (AML) blasts. HDACi produce epigenetic modifications, and may have antineoplastic effects in AML by activating transcriptional silenced genes. The mammalian target of rapamycin (mTOR) pathways constitutive activation has been involved in the pathogenesis of various cancers, including AML. We present a series of two cases of poor risk de novo and refractory elderly AML patients treated with a combination of HDACi VPA and mTOR inhibitor sirolimus (S). Methods: This is a retrospective chart review garnered data on two patients with de novo AML and refractory AML who were treated with a combination therapy of VPA 500 mg three times a day with sirolimus 1 mg by mouth daily. Patients continued to receive treatment until disease progression. Results: Patient 1 achieved transfusion independence and a 6 month CR with ECOG PS 1 without hospitalizations. Repeat BM demonstrated no morphologic or immunophenotypic evidence of AML. Persistent disease was still detectable by FISH. Patient 2 was started on the regimen after persistent disease was detected by day 14 bone marrow, post standard 7 + 3 induction. Repeat bone marrow after 23 days of treatment with VPA and Sirolimus showed no immunophenotypic, morphological or cytogenetic evidence of AML. The patient remained in remission for 9 months on therapy with normal blood counts. Conclusions: We postulate that the use of VPA with sirolimus, is an active combination therapy for elderly, poor risk AML patients who may not otherwise tolerate intensive chemotherapy. The mechanism of action may involve activation of the mTORC2 pathway by HDAC1. Given our observations, further studies are warranted to better define the activity of this or similar combination therapies in elderly AML patients. [Table: see text]
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.15_suppl.e18012
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
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