title: Therapeutic effects and pharmacokinetics of recombinant human granulocyte-macrophage colony-stimulating factor in childhood cancer patients receiving myelosuppressive chemotherapy.
abstract: Twenty-five children with refractory solid tumors were given recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in escalated doses of 60 to 1,500 micrograms/m2 as 2-hour intravenous infusions, beginning 24 hours after myelosuppressive treatment with cisplatin and etoposide. Tolerance to rhGM-CSF was exceptional even at dose levels that exceeded the maximum-tolerated dosage (MTD) reported for adults. The agent produced dose-related increases in platelet and neutrophil counts, resulting in significantly shorter durations of severe neutropenia and thrombocytopenia (P less than .01 for each analysis). At the higher dosages (greater than or equal to 750 micrograms/m2), treatment with rhGM-CSF reduced the median number of days of antibiotic therapy for fever and neutropenia by approximately one half. We conclude that rhGM-CSF is well tolerated by leukopenic children in doses as high as 1,500 micrograms/m2. An MTD was not reached in this study. The ability of the growth factor to reduce severe neutropenia and thrombocytopenia suggests it will have an important role in the management of childhood solid tumors.
authors.affiliation: Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN 38101-0318.
authors.forename: W L
authors.initials: WL
authors.lastname: Furman
authors.forename: D L
authors.initials: DL
authors.lastname: Fairclough
authors.forename: R D
authors.initials: RD
authors.lastname: Huhn
authors.forename: C B
authors.initials: CB
authors.lastname: Pratt
authors.forename: N
authors.initials: N
authors.lastname: Stute
authors.forename: W P
authors.initials: WP
authors.lastname: Petros
authors.forename: W E
authors.initials: WE
authors.lastname: Evans
authors.forename: L C
authors.initials: LC
authors.lastname: Bowman
authors.forename: E C
authors.initials: EC
authors.lastname: Douglass
authors.forename: V M
authors.initials: VM
authors.lastname: Santana
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006207:Half-Life; D006760:Hospitalization; D006801:Humans; D007223:Infant; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control*; D009504:Neutrophils / Q000187:drug effects; D010976:Platelet Count / Q000187:drug effects; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D011994:Recombinant Proteins; D005047:Etoposide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002945:Cisplatin