title: Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia.
abstract: The purpose of our study was (i) to evaluate the impact of all-trans retinoic acid (ATRA) given as adjunct to chemotherapy and (ii) to compare second consolidation vs maintenance therapy in elderly patients with acute myeloid leukemia (AML). A total of 242 patients aged >or=61 years (median, 66.6 years) with AML were randomly assigned to ATRA beginning on day +3 after the initiation of chemotherapy (ATRA-arm, n=122) or no ATRA (standard-arm, n=120) in combination with induction and first consolidation therapy. A total of 61 patients in complete remission (CR) were randomly assigned to second intense consolidation (n=31) or 1-year oral maintenance therapy (n=30). After induction therapy the intention-to-treat analysis revealed a significant difference in CR rates between the ATRA- and the standard-arm (52 vs 39%; P=0.05). Event-free (EFS) and overall survival (OS) were significantly better in the ATRA-compared to the standard-arm (P=0.03 and 0.01, respectively). OS after second randomization was significantly better for patients assigned to intensive consolidation therapy (P<0.001). The multivariate model for survival revealed lactate dehydrogenase, cytogenetic risk group, age, and first and second randomization as prognostic variables. In conclusion, the addition of ATRA to induction and consolidation therapy may improve CR rate, EFS and OS in elderly patients with AML.
authors.affiliation: Department of Internal Medicine III, University of Ulm, Ulm, Germany. Richard.Schlenk@medizin.uni-ulm.de <Richard.Schlenk@medizin.uni-ulm.de>
authors.forename: R F
authors.initials: RF
authors.lastname: Schlenk
authors.forename: S
authors.initials: S
authors.lastname: Fröhling
authors.forename: F
authors.initials: F
authors.lastname: Hartmann
authors.forename: J Th
authors.initials: JT
authors.lastname: Fischer
authors.forename: A
authors.initials: A
authors.lastname: Glasmacher
authors.forename: F
authors.initials: F
authors.lastname: del Valle
authors.forename: W
authors.initials: W
authors.lastname: Grimminger
authors.forename: K
authors.initials: K
authors.lastname: Götze
authors.forename: C
authors.initials: C
authors.lastname: Waterhouse
authors.forename: R
authors.initials: R
authors.lastname: Schoch
authors.forename: H
authors.initials: H
authors.lastname: Pralle
authors.forename: H G
authors.initials: HG
authors.lastname: Mergenthaler
authors.forename: M
authors.initials: M
authors.lastname: Hensel
authors.forename: E
authors.initials: E
authors.lastname: Koller
authors.forename: H
authors.initials: H
authors.lastname: Kirchen
authors.forename: J
authors.initials: J
authors.lastname: Preiss
authors.forename: H
authors.initials: H
authors.lastname: Salwender
authors.forename: H G
authors.initials: HG
authors.lastname: Biedermann
authors.forename: S
authors.initials: S
authors.lastname: Kremers
authors.forename: F
authors.initials: F
authors.lastname: Griesinger
authors.forename: A
authors.initials: A
authors.lastname: Benner
authors.forename: B
authors.initials: B
authors.lastname: Addamo
authors.forename: K
authors.initials: K
authors.lastname: Döhner
authors.forename: R
authors.initials: R
authors.lastname: Haas
authors.forename: H
authors.initials: H
authors.lastname: Döhner
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000754:Anemia, Refractory, with Excess of Blasts / Q000628:therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007951:Leukemia, Myeloid / Q000628:therapy*; D008875:Middle Aged; D011379:Prognosis; D012074:Remission Induction; D015996:Survival Rate; D014184:Transplantation, Homologous; D014212:Tretinoin / Q000008:administration & dosage
chemical_list: D003561:Cytarabine; D014212:Tretinoin; D005047:Etoposide; D015255:Idarubicin