title: Results of a randomized double-blind placebo-controlled trial evaluating sequential high-dose cytosine arabinoside/mitoxantrone chemotherapy with or without granulocyte/macrophage-colony-stimulating factor in high-risk myelodysplastic syndromes.
abstract: A prospective, randomized, double-blind placebo-controlled trial was designed to evaluate the impact of granulocyte/macrophage-colony-stimulating factor (GM-CSF) on the efficacy of sequential high-dose cytosine arabinoside/mitoxantrone chemotherapy (S-HAM) in adult patients with high-risk myelodysplastic syndromes (MDS). GM-CSF or placebo was given subcutaneously once daily at a dose of 250 microg/m2, starting 48 h prior to chemotherapy, and continued until neutrophil recovery. Owing to high toxicity and slow patient recruitement the study was closed and unblinded after 31 patients had been enrolled; 15 were randomized to receive placebo and 16 to receive GM-CSF. A total of 29 patients were evaluable for response; their median age was 57 years. Ten patients achieved a complete remission (34.5%), 9 patients had persistent MDS (31%), 10 patients died within 6 weeks after the onset of treatment (early death) (34.5%). The median remission duration was 190 days (range: 2.5-45 months). Among the 29 evaluable patients no significant differences could be found between the two study arms regarding complete remission rate [GM-CSF: 31% (5/16) versus placebo: 38% (5/13) P = 0.45], rate of persistent MDS [GM-CSF: 25% (4/16) versus 38% (5/13) P = 0.35), early death rate [44% (7/16) versus 23% (3/13) P = 0.22] and remission duration (GM-CSF: 87 days versus placebo 221 days). Duration of granulocytopenia (median: 33 days with GM-CSF) versus 35 days with placebo) and frequency of infectious episodes were not significantly influenced by GM-CSF. The small number of patients finally analyzed means that no definite conclusions about the effect of GM-CSF can be reached.
authors.affiliation: Department of Hematology/Oncology, Georg-August-University Göttingen, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Verbeek
authors.forename: B
authors.initials: B
authors.lastname: Wörmann
authors.forename: P
authors.initials: P
authors.lastname: Koch
authors.forename: C
authors.initials: C
authors.lastname: Aul
authors.forename: H F
authors.initials: HF
authors.lastname: Hinrichs
authors.forename: L
authors.initials: L
authors.lastname: Balleisen
authors.forename: J M
authors.initials: JM
authors.lastname: Rowe
authors.forename: J
authors.initials: J
authors.lastname: Bennett
authors.forename: D
authors.initials: D
authors.lastname: Haase
authors.forename: C
authors.initials: C
authors.lastname: Fonatsch
authors.forename: A
authors.initials: A
authors.lastname: Heinecke
authors.forename: T
authors.initials: T
authors.lastname: Büchner
authors.forename: W
authors.initials: W
authors.lastname: Hiddemann
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D004311:Double-Blind Method; D005069:Evaluation Studies as Topic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006403:Hematologic Tests; D006801:Humans; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000401:mortality; D009503:Neutropenia / Q000188:drug therapy; D010919:Placebos; D012074:Remission Induction / Q000379:methods; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D010919:Placebos; D003561:Cytarabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008942:Mitoxantrone