title: Filgrastim in patients with chemotherapy-induced febrile neutropenia. A double-blind, placebo-controlled trial.
abstract: OBJECTIVE
  To determine if filgrastim (recombinant human methionyl granulocyte colony-stimulating factor) used in addition to standard inpatient antibiotic therapy accelerated recovery from infection associated with chemotherapy-induced neutropenia.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled trial.
  
  
  METHODS
  Hematology and oncology wards of four teaching hospitals.
  
  
  METHODS
  218 patients with cancer who had fever (temperature > 38.2 degrees C) and neutropenia (neutrophil count < 1.0 x 10(9)/L) after chemotherapy.
  
  
  METHODS
  Patients were randomly assigned to receive filgrastim (12 micrograms/kg of body weight per day) (n = 109) or placebo (n = 107) beginning within 12 hours of empiric therapy with tobramycin and piperacillin. Patients received treatment and remained in the study until the neutrophil count was greater than 0.5 x 10(9)/L and until 4 days without fever (temperature < 37.5 degrees C) had elapsed.
  
  
  METHODS
  Days of neutropenia and fever and days in the study (hospitalization); time to resolution of fever and febrile neutropenia; and frequency of the use of alternative antibiotics.
  
  
  RESULTS
  Compared with placebo, filgrastim reduced the median number of days of neutropenia (3.0 compared with 4.0 days of a neutrophil count of < 0.5 x 10(9)/L; P = 0.005) and the time to resolution of febrile neutropenia (5.0 compared with 6.0 days; P = 0.01) but not days of fever (3.0 days for both groups). The frequency of the use of alternative antibiotics was similar in the two groups (46% compared with 41%; P = 0.48). The median number of days patients were hospitalized while on study was the same (8.0 days; P = 0.09); however, filgrastim decreased the risk for prolonged hospitalization (> 11 days, 4th quartile) by half (relative risk, 2.1 [95% CI, 1.1 to 4.1]; P = 0.02). In exploratory subset analyses, filgrastim appeared to provide the greatest benefit in patients with documented infection and in patients presenting with neutrophil counts of less than 0.1 x 10(9)/L.
  
  
  CONCLUSIONS
  Filgrastim treatment used with antibiotics at the onset of febrile neutropenia in patients with cancer who have received chemotherapy accelerated neutrophil recovery and shortened the duration of febrile neutropenia.
authors.affiliation: Melbourne Tumor Biology Branch, Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Victoria, Australia.
authors.forename: D W
authors.initials: DW
authors.lastname: Maher
authors.forename: G J
authors.initials: GJ
authors.lastname: Lieschke
authors.forename: M
authors.initials: M
authors.lastname: Green
authors.forename: J
authors.initials: J
authors.lastname: Bishop
authors.forename: R
authors.initials: R
authors.lastname: Stuart-Harris
authors.forename: M
authors.initials: M
authors.lastname: Wolf
authors.forename: W P
authors.initials: WP
authors.lastname: Sheridan
authors.forename: R F
authors.initials: RF
authors.lastname: Kefford
authors.forename: J
authors.initials: J
authors.lastname: Cebon
authors.forename: I
authors.initials: I
authors.lastname: Olver
authors.forename: J
authors.initials: J
authors.lastname: McKendrick
authors.forename: G
authors.initials: G
authors.lastname: Toner
authors.forename: K
authors.initials: K
authors.lastname: Bradstock
authors.forename: M
authors.initials: M
authors.lastname: Lieschke
authors.forename: S
authors.initials: S
authors.lastname: Cruickshank
authors.forename: D K
authors.initials: DK
authors.lastname: Tomita
authors.forename: E W
authors.initials: EW
authors.lastname: Hoffman
authors.forename: R M
authors.initials: RM
authors.lastname: Fox
authors.forename: G
authors.initials: G
authors.lastname: Morstyn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007239:Infections / Q000188:drug therapy* / Q000209:etiology; D007902:Length of Stay; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy*; D009504:Neutrophils; D010878:Piperacillin / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D014031:Tobramycin / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim; D014031:Tobramycin; D010878:Piperacillin