title: Randomized placebo-controlled trial of granulocyte-macrophage colony-stimulating factor in patients with chemotherapy-related febrile neutropenia.
abstract: OBJECTIVE
  To determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) used in addition to standard inpatient antibiotic therapy shortens the period of hospitalization due to chemotherapy-induced neutropenic fever.
  
  
  METHODS
  One hundred thirty-four patients with a hematologic (n = 47) or solid tumor (n = 87) who had severe neutropenia (< 0.5 x 10(9)/L) and fever (> 38.5 degrees C once or > 38 degrees C twice over a 12-hour observation period) were randomly assigned to receive GM-CSF 5 micrograms/kg/d (n = 65) or placebo (n = 69) in conjunction with broad-spectrum antibiotics for a minimum of 4 days and a maximum of 14 days. GM-CSF/placebo and antibiotics were stopped if the neutrophil count was greater than 1.0 x 10(9)/L and temperature less than 37.5 degrees C during 2 consecutive days, or for a leukocyte count > or = 10 x 10(9)/L, both followed by a 24-hour observation period (hospitalization period).
  
  
  RESULTS
  Compared with placebo, GM-CSF enhanced neutrophil recovery. Median neutrophil counts at day 4 were 2.5 x 10(9)/L (range, 0 to 25) in the GM-CSF arm and 1.3 x 10(9)/L (range, 0 to 9) in the placebo arm (P < .001). No significant difference was observed with regard to median number of days with less than 1.0 x 10(9)/L neutrophils (4 v 4) or days of fever (3 v 3). The median number of days patients were hospitalized while on study was comparable in the GM-CSF and placebo groups at 6 (range, 3 to 14) versus 7 (range, 4 to 14), respectively, according to an intention-to-treat analysis (P = .27). Quality-of-life scores in 90 patients demonstrated significant differences in favor of the placebo group. Hospital costs were significantly higher for GM-CSF-treated patients if GM-CSF was included in the price (median costs, $4,140 [US] for GM-CSF v $590 for placebo; P < .05).
  
  
  CONCLUSIONS
  These results indicate that GM-CSF does not affect the number of days for resolution of fever or the hospitalization period for this patient group, although a significant effect of GM-CSF was observed on neutrophil recovery.
authors.affiliation: Department of Hematology, University Hospital Groningen, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Vellenga
authors.forename: C A
authors.initials: CA
authors.lastname: Uyl-de Groot
authors.forename: R
authors.initials: R
authors.lastname: de Wit
authors.forename: H J
authors.initials: HJ
authors.lastname: Keizer
authors.forename: B
authors.initials: B
authors.lastname: Löwenberg
authors.forename: M A
authors.initials: MA
authors.lastname: ten Haaft
authors.forename: T J
authors.initials: TJ
authors.lastname: de Witte
authors.forename: C A
authors.initials: CA
authors.lastname: Verhagen
authors.forename: G J
authors.initials: GJ
authors.lastname: Stoter
authors.forename: F F
authors.initials: FF
authors.lastname: Rutten
authors.forename: N H
authors.initials: NH
authors.lastname: Mulder
authors.forename: W M
authors.initials: WM
authors.lastname: Smid
authors.forename: E G
authors.initials: EG
authors.lastname: de Vries
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000009:adverse effects*; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D005334:Fever; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007902:Length of Stay; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications; D009503:Neutropenia / Q000139:chemically induced / Q000191:economics / Q000628:therapy*; D011788:Quality of Life
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D016207:Cytokines; D016179:Granulocyte Colony-Stimulating Factor