title: A multicenter phase II trial of decitabine as first-line treatment for older patients with acute myeloid leukemia judged unfit for induction chemotherapy.
abstract: BACKGROUND
  The treatment of acute myeloid leukemia of older, medically non-fit patients still poses a highly unmet clinical need, and only few large, prospective studies have been performed in this setting. Given the established activity of hypomethylating agents such as 5-aza-2'-deoxycytidine (decitabine) in myelodysplastic syndromes and acute myeloid leukemia with 20-30% bone marrow blasts, we investigated whether this drug is also active in patients with more than 30% blasts.
  
  
  METHODS
  To evaluate the efficacy and toxicity of decitabine in patients over 60 years old with untreated acute myeloid leukemia ineligible for induction chemotherapy, 227 patients (median age, 72 years), many with comorbidities, adverse cytogenetics and/or preceding myelodysplastic syndrome were treated with this hypomethylating agent. During the initial decitabine treatment (135 mg/m(2) total dose infused intravenously over 72 hours every 6 weeks), a median of two cycles was administered (range, 1-4). All-trans retinoic acid was administered to 100 patients during course 2. Fifty-two patients who completed four cycles of treatment subsequently received a median of five maintenance courses (range, 1-19) with a lower dose of decitabine (20 mg/m(2)) infused over 1 hour on 3 consecutive days every 4-6 weeks.
  
  
  RESULTS
  The complete and partial remission rate was 26%, 95% CI (20%, 32%), and an antileukemic effect was noted in 26% of patients. Response rates did not differ between patients with or without adverse cytogenetics; patients with monosomal karyotypes also responded. The median overall survival from the start of decitabine treatment was 5.5 months (range, 0-57.5+) and the 1-year survival rate was 28%, 95%CI (22%,34%). Toxicities were predominantly hematologic.
  
  
  CONCLUSIONS
  Decitabine is well tolerated by older, medically non-fit patients with acute myeloid leukemia; myelosuppression is the major toxicity. The response rate and overall survival were not adversely influenced by poor-risk cytogenetics or myelodysplastic syndrome. Because of these encouraging results, randomized studies evaluating single-agent decitabine versus conventional treatment are warranted. The study is registered with the German Clinical Trials Registry, number DRKS00000069.
authors: Dept. of Medicine, Div. Hematology/Oncology, University of Freiburg Medical Center, Hugstetter Str. 55, D-79106 Freiburg, Germany. michael.luebbert@uniklinik-freiburg.de
authors: Michael
authors: M
authors: Lübbert
authors: Björn H
authors: BH
authors: Rüter
authors: Rainer
authors: R
authors: Claus
authors: Claudia
authors: C
authors: Schmoor
authors: Mathias
authors: M
authors: Schmid
authors: Ulrich
authors: U
authors: Germing
authors: Andrea
authors: A
authors: Kuendgen
authors: Volker
authors: V
authors: Rethwisch
authors: Arnold
authors: A
authors: Ganser
authors: Uwe
authors: U
authors: Platzbecker
authors: Oliver
authors: O
authors: Galm
authors: Wolfram
authors: W
authors: Brugger
authors: Gerhard
authors: G
authors: Heil
authors: Björn
authors: B
authors: Hackanson
authors: Barbara
authors: B
authors: Deschler
authors: Konstanze
authors: K
authors: Döhner
authors: Anne
authors: A
authors: Hagemeijer
authors: Pierre W
authors: PW
authors: Wijermans
authors: Hartmut
authors: H
authors: Döhner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015897:Comorbidity; D000077209:Decitabine; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine