García-Carbonero, RocíoMayordomo, Jose IgnacioTornamira, María VLópez-Brea, MartaRueda Domínguez, AntonioGuillém, VicenteArcediano, AlbertoYubero, AlfonsoRibera, FernandoGómez, CarlosTrés, AlejandroPérez-Gracia, José LLumbreras, CarlosHornedo, JavierCortés-Funes, HernanPaz-Ares, Luis2013-01-142013-01-142001-01-03García-Carbonero R, Mayordomo JL, Tornamira MV, López-Brea M, Rueda Domínguez A, Guillém V, et al. Granulocyte colony-stimulating factor in the treatment of high-risk febrile neutropenia: a multicenter randomized trial. J. Natl. Cancer Inst.. 2001; 93(1):31-80027-8874http://hdl.handle.net/10668/741Presented in part at the 35th American Society of Clinical Oncology meeting. Atlanta (GA); 1999. Clinical Trial; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't;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/mm(3)), 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 microg/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 = 0.0004), antibiotic therapy (median, 5 days versus 6 days; P = 0.013), and hospital stay (median, 5 days versus 7 days; P = 0.015) 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 = 0.12), 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 = 0.01) and by 11% (P = 0.07), 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.enAntibacterianosProtocolos de Quimioterapia Combinada AntineoplásicaAnálisis Costo-BeneficioEsquema de MedicaciónFiebreFactor Estimulante de Colonias de GranulocitosTiempo de InternaciónNeoplasiasEspañaModelos de Riesgos ProporcionalesAnálisis de SupervivenciaFactores de TiempoResultado del TratamientoMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial AgentsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Clinical Protocols::Antineoplastic Protocols::Antineoplastic Combined Chemotherapy ProtocolsMedical Subject Headings::Health Care::Health Care Economics and Organizations::Economics::Costs and Cost Analysis::Cost-Benefit AnalysisMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Administration ScheduleMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Temperature Changes::FeverMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Hematopoietic Cell Growth Factors::Colony-Stimulating Factors::Granulocyte Colony-Stimulating FactorMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Health Care::Health Care Facilities, Manpower, and Services::Health Services::Patient Care::Hospitalization::Length of StayMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Diseases::NeoplasmsMedical Subject Headings::Diseases::Hemic and Lymphatic Diseases::Hematologic Diseases::Leukocyte Disorders::Leukopenia::Agranulocytosis::NeutropeniaMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Proportional Hazards ModelsMedical Subject Headings::Geographicals::Geographic Locations::Europe::SpainMedical Subject Headings::Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Survival AnalysisMedical Subject Headings::Phenomena and Processes::Physical Phenomena::Time::Time FactorsMedical Subject Headings::Health Care::Health Services Administration::Quality of Health Care::Outcome and Process Assessment (Health Care)::Outcome Assessment (Health Care)::Treatment OutcomeMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Agedresearch article11136839open access10.1093/jnci/93.1.311460-2105