title: Chemomodulation of sequential high-dose cytarabine by fludarabine in relapsed or refractory acute myeloid leukemia: a randomized trial of the AMLCG.
abstract: Chemomodulation of cytarabine by fludarabine has been attributed with a higher antileukemic efficacy, but randomized trials to address this question are rare. We therefore conducted a multicenter, randomized phase III study to evaluate the antileukemic efficacy of adding fludarabine to sequential high-dose cytarabine+idarubicin (SHAI) re-induction chemotherapy in relapsed or refractory acute myeloid leukemia (AML). Patients (n=326, of which 281 were evaluable) were randomly assigned to SHAI (cytarabine, 1 g/m(2) bid, days 1-2 and 8-9 (3 g/m(2) for patients ≤ 60 years with refractory AML or ≥ 2nd relapse); idarubicin 10 mg/m(2) daily, days 3-4 and 10-11) or F-SHAI (SHAI with fludarabine, 15 mg/m(2), 4 h before cytarabine). Although complete remission (CR) rates (35% SHAI and 44% F-SHAI) and overall survival did not differ between both regimens, fludarabine prolonged time to treatment failure from 2.04 to 3.38 months (median, P<0.05). Twenty-seven percent of patients proceeded to allogeneic stem cell transplantation, with a significantly higher number of patients in CR or incomplete remission in the F-SHAI group (22 vs 10%, P<0.01). In conclusion, fludarabine has a beneficial, although moderate, impact on the antileukemic efficacy of high-dose cytarabine-based salvage therapy for relapsed and refractory AML.
authors.affiliation: Department of Internal Medicine III, University Hospital of Munich, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Fiegl
authors.affiliation: Department of Internal Medicine III, University Hospital of Munich, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Unterhalt
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Kern
authors.affiliation: Department of Hematology and Oncology, Klinikum Barmherzige Brüder, Regensburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Braess
authors.affiliation: Department of Internal Medicine III, University Hospital of Munich, Munich, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Spiekermann
authors.affiliation: Department of Hematology and Oncology, St-Antonius-Hospital, Eschweiler, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Staib
authors.affiliation: Department of Hematology and Oncology, Vivantes Klinikum Berlin-Neukölln, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Grüneisen
authors.affiliation: German Society for Hematology and Oncology, Berlin, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Wörmann
authors.affiliation: Department of Hematology and Oncology, Helios Klinikum Berlin Buch, Berlin, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Schöndube
authors.affiliation: Department of Hematology and Oncology, J.W. Goethe-University, Frankfurt, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Serve
authors.affiliation: Department of Internal Medicine II, University Hospital of Regensburg, Regensburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Reichle
authors.affiliation: Department of Hematology and Oncology, Krankenhaus Harlaching, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hentrich
authors.affiliation: Department of Hematology and Oncology, Krankenhaus Harlaching, Munich, Germany.
authors.forename: X
authors.initials: X
authors.lastname: Schiel
authors.affiliation: Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Sauerland
authors.affiliation: Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Heinecke
authors.affiliation: Department of Internal Medicine III, University Hospital of Munich, Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Rieger
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, University of Essen, Essen, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Beelen
authors.affiliation: Department of Medicine A, Hematology and Oncology, University of Muenster, Muenster, Germany.
authors.forename: W E
authors.initials: WE
authors.lastname: Berdel
authors.affiliation: Department of Medicine A, Hematology and Oncology, University of Muenster, Muenster, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Büchner
authors.affiliation: Department of Internal Medicine III, University Hospital of Munich, Munich, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Hiddemann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D016019:Survival Analysis; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D003561:Cytarabine; D014740:Vidarabine; C024352:fludarabine