Filgrastim in patients with chemotherapy-induced febrile neutropenia. A double-blind, placebo-controlled trial

D. W. Maher*, G. J. Lieschke, M. Green, J. Bishop, R. Stuart-Harris, M. Wolf, W. P. Sheridan, R. F. Kefford, J. Cebon, I. Olver, J. McKendrick, G. Toner, K. Bradstock, M. Lieschke, S. Cruickshank, D. K. Tomita, E. W. Hoffman, R. M. Fox, G. Morstyn

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

218 Citations (Scopus)


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. Design: Randomized, double-blind, placebo-controlled trial. Setting: Hematology and oncology wards of four teaching hospitals. Patients: 218 patients with cancer who had fever (temperature > 38.2°C) and neutropenia (neutrophil count < 1.0 x 109/L) after chemotherapy. Intervention: Patients were randomly assigned to receive filgrastim (12 μg/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 109/L and until 4 days without fever (temperature < 37.5°C) had elapsed. Measurements: 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 109/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 109/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.

Original languageEnglish
Pages (from-to)492-501
Number of pages10
JournalAnnals of Internal Medicine
Issue number7
Publication statusPublished - 1994
Externally publishedYes


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