Darryl W. Maher, MMB, BS, PhD; Graham J. Lieschke, BMedSci, MB, BS; Michael Green, MB, BS; James Bishop, MD; Robin Stuart-Harris, MD; Max Wolf, MB, BS; William P. Sheridan, MB, BS; Richard F. Kefford, MB, BS, PhD; Jonathan Cebon, MB, BS, PhD; Ian Olver, MD; Joseph McKendrick, MB, BS, DM; Guy Toner, MB, BS; Kenneth Bradstock, MB, BS, PhD; Marian Lieschke, BA, RN; Scott Cruickshank, MA; Dianne K. Tomita, MPH; Eric W. Hoffman, PharmD; Richard M. Fox, MB, BS, PhD; George Morstyn, MB, BS, PhD
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.
Randomized, double-blind, placebo-controlled trial.
Hematology and oncology wards of four teaching hospitals.
218 patients with cancer who had fever (temperature >38.2 °C) and neutropenia (neutrophil count <1.0 × 109/L) after chemotherapy.
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 × 109/L and until 4 days without fever (temperature <37.5 °C) had elapsed.
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.
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 × 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 × 109/L.
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.
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Maher DW, Lieschke GJ, Green M, Bishop J, Stuart-Harris R, Wolf M, et al. Filgrastim in Patients with Chemotherapy-Induced Febrile Neutropenia: A Double-Blind, Placebo-Controlled Trial. Ann Intern Med. 1994;121:492-501. doi: 10.7326/0003-4819-121-7-199410010-00004
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Published: Ann Intern Med. 1994;121(7):492-501.
Hematology/Oncology, Hospital Medicine, Prevention/Screening.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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