title: Phase 1 safety trial of Filgrastim (r-metHuG-CSF) in non-neutropenic patients with severe community-acquired pneumonia.
abstract: The objectives of the present study were to: (1) evaluate the safety of Filgrastim therapy in non-neutropenic patients with severe community-acquired pneumonia; (2) determine the absolute neutrophil count (ANC) response to various dosages of Filgrastim in non-neutropenic patients with active infection; and (3) describe the impact of therapy with Filgrastim in combination with antibiotics on selected pneumonia-related clinical parameters. The study design was an open-label, dose-ranging, clinical trial, set in the General Clinical Research Unit of a large, public community hospital. The study population consisted of 30 patients who had presented to the Emergency Department with severe, community-acquired pneumonia. One of five dosages (75, 150, 300, 450 or 600 micrograms day-1) of Filgrastim (r-metHuG-CSF) was given subcutaneously daily for 10 days, until discharge or until the absolute neutrophil count > 75 x 10(9) l(-1), whichever was earlier. Vital signs, pulse oximetry, arterial blood gases, daily complete blood counts with differential, serum chemistries, coagulation profiles, electrocardiograms, chest radiographs, plasma G-CSF concentrations and duration of hospitalization were measured. There was no evidence of Filgrastim-related lung injury or evidence of extra-pulmonary toxicity. There was no apparent dose-response effect of Filgrastim on pneumonia-related clinical variables. Dosages of Filgrastim between 150 and 600 micrograms day-1 had similar effects on increasing the ANC. Filgrastim appeared to be safe in non-neutropenic patients with severe, community-acquired pneumonia when given in dosages of 75-600 micrograms day-1 in combination with appropriate antibiotic therapy. Further study is needed to determine the effect of Filgrastim on morbidity, mortality and duration of symptoms in this patient population.
authors.affiliation: Department of Medicine, Louisiana State University Medical School, New Orleans, USA.
authors.forename: B P
authors.initials: BP
authors.lastname: deBoisblanc
authors.forename: C M
authors.initials: CM
authors.lastname: Mason
authors.forename: J
authors.initials: J
authors.lastname: Andresen
authors.forename: E
authors.initials: E
authors.lastname: Logan
authors.forename: M B
authors.initials: MB
authors.lastname: Bear
authors.forename: S
authors.initials: S
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Shellito
authors.forename: W R
authors.initials: WR
authors.lastname: Summer
authors.forename: S
authors.initials: S
authors.lastname: Nelson
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D017714:Community-Acquired Infections / Q000097:blood / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005334:Fever / Q000628:therapy; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D007902:Length of Stay; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology*; D018410:Pneumonia, Bacterial / Q000097:blood / Q000628:therapy*; D011994:Recombinant Proteins
chemical_list: D000900:Anti-Bacterial Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim