Clinical outcome of treatment with a combined regimen of decitabine and aclacinomycin/cytarabine for patients with refractory acute myeloid leukemia.

Abstract

We conducted a clinical trial of low-dose decitabine plus aclacinomycin/cytarabine (AA) treatment (DAA) for 20 patients with refractory/relapsed de novo acute myeloid leukemia (AML) or AML transformed from myelodysplastic syndrome (MDS/AML) in order to examine its efficacy and tolerability. Additionally, P15(ink4b) methylation status was analyzed (for 15 patients) pre- and post-DAA treatment, and in vitro drug sensitivity tests were performed for seven patients (AA or AA + decitabine) to explore the role of decitabine in this combination treatment regimen. A total of 11 patients (55.0 %) achieved complete remission (CR) after DAA treatment, including 7 of whom reached CR after only one treatment course. The other two patients achieved partial remission. The median overall survival (OS) was 10 months for all 20 patients. The median OS for those who achieved CR was significantly longer than that of patients with no response (NR; P = 0.01). The treatment regimen was well tolerated, and there was no treatment-related mortality. The mean levels of P15(ink4b) methylation decreased significantly in six patients who achieved CR, whereas very few changes in P15 (ink4b) methylation were detected for the five patients with NR following DAA treatment. The data from the methyl thiazolyl tetrazolium assays showed that the inhibition rates of AA and DAA for tumor cells were identical. We conclude that induction therapy with DAA for refractory/relapsed de novo AML or MDS/AML achieved high levels of CR and improved OS and demonstrated adequate tolerance. Moreover, the decitabine component of DAA may function through a demethylation effect.

• Authors: Lu Xi Song, Li Xu, Xiao Li, Chun Kang Chang, Yi Zhang, Ling Yun Wu, Qi He, Qing Xia Zhang, Xiang Li
• Journal: Annals of hematology (Ann Hematol) Vol. 91 Issue 12 Pg. 1879-86 (Dec 2012) ISSN: 1432-0584 [Electronic] Germany
• PMID: 22895556 (Publication Type: Controlled Clinical Trial, Journal Article)

Chemical References

• CDKN2B protein, human
• Cyclin-Dependent Kinase Inhibitor p15
• Enzyme Inhibitors
• aclacinomycins
• Cytarabine
• Aclarubicin
• Decitabine
• DNA Modification Methylases
• Azacitidine

Topics

• Aclarubicin (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Azacitidine (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Cell Survival (drug effects)
• Cyclin-Dependent Kinase Inhibitor p15 (genetics, metabolism)
• Cytarabine (administration & dosage, adverse effects, therapeutic use)
• DNA Methylation (drug effects)
• DNA Modification Methylases (antagonists & inhibitors)
• Decitabine
• Drug Resistance, Neoplasm
• Enzyme Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Female
• Humans
• Leukemia, Myeloid, Acute (drug therapy, metabolism)
• Leukocytes, Mononuclear (drug effects)
• Male
• Middle Aged
• Recurrence
• Remission Induction
• Survival Analysis
• Tumor Cells, Cultured
• Young Adult