title: A randomized, double-blind, placebo-controlled study with pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) as an adjunct to chemotherapy for adults with de novo acute myeloid leukemia.
abstract: To determine the safety, biologic, and clinical benefits of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF; Amgen, Thousand Oaks, CA) after myelosuppressive chemotherapy in acute myeloid leukemia (AML), 108 adult patients with de novo AML were randomized to receive either PEG-rHuMGDF (2.5 microg/kg/d or 5 microg/kg/d) for up to 21 doses (group A), a single dose of 2.5 microg/kg PEG-rHuMGDF, 7 daily doses of 2.5 microg/kg PEG-rHuMGDF (group B), or placebo. The greatest biologic activity was seen in group A with a median peak platelet count of 1,084 x 10(9)/L, occurring at a median 9 days after the last dose of study drug, compared with 517 x 10(9)/L and 390 x 10(9)/L in group B and placebo group, respectively. Thrombocytosis (platelets >1,000 x 10(9)/L) was seen at rates of 52%, 8%, and 9% in groups A, B, and placebo, respectively, but were not associated with any adverse event. There was no effect on median time to transfusion independent platelet recovery (> or = 20 x 10(9)/L). The median time to neutrophil recovery (> or = 500/microL) and red blood cell transfusion requirements were similar in all groups, and there was no apparent stimulation of leukemia. PEG-rHuMGDF was biologically active and well tolerated. Further investigation of dose and scheduling is required, specifically earlier dosing before and during chemotherapy.
authors.affiliation: Hôpital Edouard Herriot, Lyon, France.
authors.forename: E
authors.initials: E
authors.lastname: Archimbaud
authors.forename: O G
authors.initials: OG
authors.lastname: Ottmann
authors.forename: J A
authors.initials: JA
authors.lastname: Yin
authors.forename: K
authors.initials: K
authors.lastname: Lechner
authors.forename: H
authors.initials: H
authors.lastname: Dombret
authors.forename: M A
authors.initials: MA
authors.lastname: Sanz
authors.forename: G
authors.initials: G
authors.lastname: Heil
authors.forename: P
authors.initials: P
authors.lastname: Fenaux
authors.forename: W
authors.initials: W
authors.lastname: Brugger
authors.forename: A
authors.initials: A
authors.lastname: Barge
authors.forename: C
authors.initials: C
authors.lastname: O'Brien-Ewen
authors.forename: J
authors.initials: J
authors.lastname: Matcham
authors.forename: D
authors.initials: D
authors.lastname: Hoelzer
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D013926:Thrombopoietin / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D011092:Polyethylene Glycols; D013926:Thrombopoietin