title: Improving treatment of chemotherapy-induced neutropenic fever by administration of colony-stimulating factors.
abstract: BACKGROUND
  Several randomized trials have tested the use of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in relieving chemotherapy-induced bone marrow suppression. However, the use of CSFs in the treatment of neutropenic fever remains virtually unexplored.
  
  
  OBJECTIVE
  This study evaluated the benefits of adding CSF therapy to the standard antibiotic treatments given to cancer patients for chemotherapy-induced neutropenic fever. The usefulness of CSFs was quantified in terms of reducing the following: (a) the duration of neutropenia, (b) the length of hospitalization, and (c) the overall cost of the treatment.
  
  
  METHODS
  A randomized trial was conducted to test whether the administration of either G-CSF or GM-CSF improved the outcome of standard antibiotic therapy (ceftazidime plus amikacin) in nonleukemic cancer patients with fever (> 38 degrees C) and grade IV neutropenia (absolute neutrophil count [ANC] < 500/mm3) induced by standard-dose chemotherapy. Of 121 patients who entered the trial, 39 received G-CSF (5 micrograms/kg body weight per day), 39 received GM-CSF (5 micrograms/kg body weight per day), and 43 received a placebo beginning just after the first dose of antibiotics. Treatments were continued for at least 5 days (7 days with clinically or microbiologically documented infections) or until 2 days after fever subsided and ANCs rose above 1000/mm3.
  
  
  RESULTS
  The median duration of grade IV neutropenia (ANC of < 500/mm3) was 2 days in both CSF arms and 3 days in the placebo arm (P < .001). The median duration of neutropenia with an ANC of less than 1000/mm3 was also significantly shorter in patients receiving G-CSF or GM-CSF (P < .001). The median duration of fever was similar in the three arms. The median hospital stay was 5 days (range, 5-14 days) in the G-CSF arm, 5 days (range, 5-10 days) in the GM-CSF arm, and 7 days (range, 5-34 days) in the placebo arm (P < .001). The median time on CSF was 4 days in both treatment arms. The mean cost of overall treatment was reduced by $1300-$1400 in the CSF arms compared with the placebo arm (P = .11 for G-CSF versus placebo; P = .06 for GM-CSF versus placebo; P = .7 for G-CSF versus GM-CSF).
  
  
  CONCLUSIONS
  Adding G-CSF or GM-CSF therapy to antibiotic treatment shortens the duration of neutropenia and the duration of hospitalization in patients with neutropenic fever. A statistically nonsignificant trend toward lower cost was observed in the CSF arms as compared with the placebo arm.
  
  
  CONCLUSIONS
  The benefits of CSFs to cancer patients with chemotherapy-induced neutropenic fever merit further evaluation in large randomized trials.
authors.affiliation: Division of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: J I
authors.initials: JI
authors.lastname: Mayordomo
authors.forename: F
authors.initials: F
authors.lastname: Rivera
authors.forename: M T
authors.initials: MT
authors.lastname: Díaz-Puente
authors.forename: P
authors.initials: P
authors.lastname: Lianes
authors.forename: R
authors.initials: R
authors.lastname: Colomer
authors.forename: M
authors.initials: M
authors.lastname: López-Brea
authors.forename: E
authors.initials: E
authors.lastname: López
authors.forename: L
authors.initials: L
authors.lastname: Paz-Ares
authors.forename: R
authors.initials: R
authors.lastname: Hitt
authors.forename: I
authors.initials: I
authors.lastname: García-Ribas
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D016009:Chi-Square Distribution; D003362:Cost-Benefit Analysis; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000191:economics / Q000517:prevention & control*; D016179:Granulocyte Colony-Stimulating Factor / Q000191:economics / Q000627:therapeutic use*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000191:economics / Q000627:therapeutic use*; D006801:Humans; D007902:Length of Stay; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000191:economics / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor