Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome

摘要: In this Phase 2 study, we evaluated the efficacy of combination 5-azacitidine (AZA), valproic acid (VPA), and all-trans retinoic (ATRA) in patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Treatment consisted six cycles AZA VPA for 7 days, followed by ATRA 21 days. Sixty-five were enrolled (median age, 72 years; 55 AML including 13 relapsed/refractory patients, 10 MDS; 30 unfavorable karyotypes). Best responses included 14 CR 3 PR (26%), 75% responders 36% non-responders achieving an erythroid response. Median overall survival (OS) was 12.4 months. Untreated had a longer OS than patients. who fulfilled 6 planned cycles, did not appear to depend on CR/PR achievement, suggesting that stable disease while on-treatment would be surrogate approach. During therapy, early platelet response demethylation FZD9, ALOX12, HPN, CALCA genes associated clinical Finally, there no evidence restoration ATRA-induced differentiation during therapy. Epigenetic modulation deserves prospective comparisons conventional care AML, at least those presenting previously untreated low blast count.