Granulocyte Colony-Stimulating Factor in the Treatment of High-Risk Febrile Neutropenia: a Multicenter Randomized Trial

• Published in: JNCI : Journal of the National Cancer Institute Vol. 93; no. 1; pp. 31 - 38
• Main Authors: García-Carbonero, Rocio, Mayordomo, José I., Tornamira, María V., López-Brea, Marta, Rueda, Antonio, Guillem, Vicente, Arcediano, Alberto, Yubero, Alfonso, Ribera, Fernando, Gómez, Carlos, Trés, Alejandro, Pérez-Gracia, José L., Lumbreras, Carlos, Hornedo, Javier, Cortés-Funes, Hernan, Paz-Ares, Luis
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 03.01.2001; Oxford Publishing Limited (England)
• Subjects: Aged; Anti-Bacterial Agents - therapeutic use; Antibiotics; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; Chemotherapy; Clinical trials; Cost-Benefit Analysis; Drug Administration Schedule; Drug toxicity and drugs side effects treatment; Female; Fever - chemically induced; Fever - etiology; Fever - microbiology; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte Colony-Stimulating Factor - economics; Granulocyte Colony-Stimulating Factor - therapeutic use; Humans; Infections; Length of Stay; Male; Medical sciences; Middle Aged; Mortality; Neoplasms - drug therapy; Neutropenia - chemically induced; Neutropenia - complications; Neutropenia - drug therapy; Pharmacology. Drug treatments; Proportional Hazards Models; Prospective Studies; Spain; Survival Analysis; Time Factors; Toxicity: blood; Treatment Outcome; Europe; Spain; Antineoplastic agent; Human; Leukopenia; Toxicity; Treatment efficiency; Multicenter study; Cytokine; Hemopathy; Malignant tumor; Fever; Chemotherapy; Granulocyte colony stimulating factor; Randomization; Treatment; Polypeptide; Health economy; Complication; Clinical trial; Cost efficiency analysis; Neutropenia
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/93.1.31

Background: Granulocyte colony-stimulating factors (G-CSFs) have been shown to help prevent febrile neutropenia in certain subgroups of cancer patients undergoing chemotherapy, but their role in treating febrile neutropenia is controversial. The purpose of our study was to evaluate—in a prospective multicenter randomized clinical trial—the efficacy of adding G-CSF to broad-spectrum antibiotic treatment of patients with solid tumors and high-risk febrile neutropenia. Methods: A total of 210 patients with solid tumors treated with conventional-dose chemotherapy who presented with fever and grade IV neutropenia were considered to be eligible for the trial. They met at least one of the following high-risk criteria: profound neutropenia (absolute neutrophil count <100/mm3), short latency from previous chemotherapy cycle (<10 days), sepsis or clinically documented infection at presentation, severe comorbidity, performance status of 3–4 (Eastern Cooperative Oncology Group scale), or prior inpatient status. Eligible patients were randomly assigned to receive the antibiotics ceftazidime and amikacin, with or without G-CSF (5 μg/kg per day). The primary study end point was the duration of hospitalization. All P values were two-sided. Results: Patients randomly assigned to receive G-CSF had a significantly shorter duration of grade IV neutropenia (median, 2 days versus 3 days; P = .0004), antibiotic therapy (median, 5 days versus 6 days; P = .013), and hospital stay (median, 5 days versus 7 days; P = .015) than patients in the control arm. The incidence of serious medical complications not present at the initial clinical evaluation was 10% in the G-CSF group and 17% in the control group (P = .12), including five deaths in each study arm. The median cost of hospital stay and the median overall cost per patient admission were reduced by 17% (P = .01) and by 11% (P = .07), respectively, in the G-CSF arm compared with the control arm. Conclusions: Adding G-CSF to antibiotic therapy shortens the duration of neutropenia, reduces the duration of antibiotic therapy and hospitalization, and decreases hospital costs in patients with high-risk febrile neutropenia.