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

Objective: To determine if filgrastim (recombinant human methionyl gra nulocyte colony-stimulating factor) used in addition to standard inpat ient antibiotic therapy accelerated recovery from infection associated with chemotherapy-induced neutropenia. Design: Randomized, double-bli nd, placebo-controlled trial. Setting: Hematology and oncology wards o f 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 random ly 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 th erapy with tobramycin and piperacillin. Patients received treatment an d 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 i n the study (hospitalization); time to resolution of fever and febrile neutropenia; and frequency of the use of alternative antibiotics. Res ults: Compared with placebo, filgrastim reduced the median number of d ays of neutropenia (3.0 compared with 4.0 days of a neutrophil count o f <0.5 x 10(9)/L; P = 0.005) and the time to resolution of febrile neu tropenia (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 an tibiotics was similar in the two groups (46% compared with 41%; P = 0. 48). The median number of days patients were hospitalized while on stu dy was the same (8.0 days; P = 0.09); however, filgrastim decreased th e 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 su bset analyses, filgrastim appeared to provide the greatest benefit in patients with documented infection and in patients presenting with neu trophil counts of less than 0.1 x 10(9)/L. Conclusions: Filgrastim tre atment used with antibiotics at the onset of febrile neutropenia in pa tients with cancer who have received chemotherapy accelerated neutroph il recovery and shortened the duration of febrile neutropenia.