title: A randomized placebo-controlled phase III study of granulocyte-macrophage colony-stimulating factor in adult patients (> 55 to 70 years of age) with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490).
abstract: The treatment of adult patients greater than 55 to 70 years of age with acute myelogenous leukemia (AML) is associated with a treatment-related mortality of approximately 25%. This prospective, double-blind randomized study was designed to see if the use of granulocyte-macrophage colony stimulating factor (GM-CSF; yeast-derived) could shorten the period of neutropenia and to determine any effect this would have on therapy-related morbidity and mortality. A total of 124 patients entered this study. Induction consisted of standard daunorubicin and cytarabine. A day-10 bone marrow was examined; if this was aplastic without leukemia, patients received blinded placebo or GM-CSF from day 11 until neutrophil recovery. Patients who entered complete remission received the identical study medication (blinded GM-CSF or placebo) in consolidation that they had received during induction. The overall complete remission rate was 52%; 60% for the GM-CSF arm and 44% for the placebo arm (P = .08). Median times to neutrophil recovery were significantly shortened on the GM-CSF arm. The overall treatment-related toxicity from start of GM-CSF/placebo was reduced on the GM-CSF arm (P = .049). Similarly, the infectious toxicity was significantly reduced on the GM-CSF arm (P = .015). The median survival for all patients was 10.6 months in the GM-CSF group and 4.8 months in the placebo arm (P = .048). It appears that GM-CSF is safe and efficacious for adult patients greater than 55 to 70 years of age with AML; its major impact is in reducing the duration of neutropenia and therapy-related mortality and morbidity. This may result in a better response rate.
authors.affiliation: Hematology Unit, University of Rochester Medical Center, NY 14642, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Rowe
authors.forename: J W
authors.initials: JW
authors.lastname: Andersen
authors.forename: J J
authors.initials: JJ
authors.lastname: Mazza
authors.forename: J M
authors.initials: JM
authors.lastname: Bennett
authors.forename: E
authors.initials: E
authors.lastname: Paietta
authors.forename: F A
authors.initials: FA
authors.lastname: Hayes
authors.forename: D
authors.initials: D
authors.lastname: Oette
authors.forename: P A
authors.initials: PA
authors.lastname: Cassileth
authors.forename: E A
authors.initials: EA
authors.lastname: Stadtmauer
authors.forename: P H
authors.initials: PH
authors.lastname: Wiernik
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001856:Bone Marrow Examination; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007902:Length of Stay; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000628:therapy*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors; D011994:Recombinant Proteins; D003561:Cytarabine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003630:Daunorubicin