FILGRASTIM IN PATIENTS WITH CHEMOTHERAPY-INDUCED FEBRILE NEUTROPENIA - A DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

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 degrees C) and neutropenia (neutrophil count <1.0 x 10(9)/L) after chemotherapy. Intervention: Patients were randomly assigned to receive filgrastim (12 mu g/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. 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 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.