title: Efficacy and tolerability of treatment with azacitidine for 5 days in elderly patients with acute myeloid leukemia.
abstract: Acute myeloid leukemia (AML) patients aged ≥ 60 years tolerate standard induction chemotherapy poorly. Therapy with azacitidine at a dose of 75 mg/m(2)/day for 7 days appears to be better tolerated, and is approved by the Food and Drug Administration (FDA) for the treatment of elderly AML patients with bone marrow (BM) blast counts of 20-30%. Here, we report the results of a prospective, phase 2, open-label study that evaluated the tolerability and efficacy of a 5-day regimen of single-agent subcutaneous azacitidine 100 mg/m(2)/day administered every 28 days in 15 elderly patients with newly diagnosed AML, 14 of whom had BM blast counts >30%. The overall response rate was 47%. Complete remission, partial remission, and hematologic improvement were achieved by 20, 13, and 13% of patients, respectively. Median overall survival was 355 days for the entire cohort, and 532 days for responders. Median time to best response was 95 days, and median treatment duration was 198 days (range = 13-724 days). Grade 3-4 hematologic toxicities comprised predominantly febrile neutropenia (40%) and thrombocytopenia (20%). Febrile neutropenia was the most common cause of hospitalization. Nonhematologic toxicities, consisting of injection-site skin reactions and fatigue (Grades 1-2), occurred in 73% (n = 11) of patients. No treatment-related deaths occurred during the study. The dose and schedule of therapy remained constant in all but four patients. The findings of this study suggest that administration of subcutaneous azacitidine 100 mg/m(2)/day for 5 days every 28 days is a feasible, well-tolerated, and effective alternative to standard induction chemotherapy in elderly patients with AML.
authors.affiliation: Division of Hematology and Cellular Therapy, Allegheny Health Network, Pittsburgh, Pennsylvania, 15224.
authors.forename: Santhosh K
authors.initials: SK
authors.lastname: Sadashiv
authors.forename: Christie
authors.initials: C
authors.lastname: Hilton
authors.forename: Cyrus
authors.initials: C
authors.lastname: Khan
authors.forename: James M
authors.initials: JM
authors.lastname: Rossetti
authors.forename: Heather L
authors.initials: HL
authors.lastname: Benjamin
authors.forename: Salman
authors.initials: S
authors.lastname: Fazal
authors.forename: Entezam
authors.initials: E
authors.lastname: Sahovic
authors.forename: Richard K
authors.initials: RK
authors.lastname: Shadduck
authors.forename: John
authors.initials: J
authors.lastname: Lister
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D001374:Azacitidine / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D007279:Injections, Subcutaneous; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine
keywords: Azacitidine; acute myeloid leukemia; aged; outpatients; subcutaneous injections