Randomized comparison between antibiotics alone and antibiotics plus granulocyte-macrophage colony-stimulating factor (Escherichia coli-derived) in cancer patients with fever and neutropenia (original) (raw)
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JNCI Journal of the National Cancer Institute, 2001
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 µg/kg per day). The primary study end point was the duration of hospitalization. All P values were twosided. 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.
Kansenshogaku zasshi, 1996
The present multicenter study was performed to evaluate the effect of recombinant human granulocyte-colony stimulating factor (rhG-CSF) on combination therapy using aztreonam (AZT) and clindamycin (CLDM) to treat severe infection in neutropenic patients with hematologic diseases. Forty-three neutropenic patients with infections (rhG-CSF group) were treated with AZT (2 g) and CLDM (600 mg) 2-3 times daily as well as rhG-CSF (Lenograstim or Filgrastim: 2-5 id/kg/day). The clinical efficacy of this regimen was compared to that obtained in 44 febrile neutropenic patients, with hematologic diseases, who received only AZT and CLDM in a previous study (historical control group). The overall efficacy rate was 69.8% (30/43) in the rhG-CSF group and 65.9% (29/44) in the historical control group. Although the neutrophil count was significantly increased and C-reactive protein tended to be lower in the rhG-CSF group, the daily maximum body temperature profiles of the 2 groups were nearly the same. These results suggest that rhG-CSF is of little benefit in the treatment of single infectious episodes in neutropenic patients, and that appropriate antibiotic therapy is more important.
The clinical utility of granulocyte colony‐stimulating factor: Early achievements and future promise
Stem Cells, 1994
Recombinant granulocyte colonystimulating factor (rHuG-CSF) is a hematopoietic growth factor that acts selectively on the nentrophil lineage, and has had a major impact on clinical practice. Two forms are in clinical use: filgrastim has been approved for use in more than 45 countries for the amelioration of chemotherapy-induced neutropenia and restoration of granulopoiesis following bone-marrow transplantation and lenograstim has been approved in Europe and Japan. In some countries, rHuG-CSF is also approved for various other indications, such as severe chronic neutropenia. Infection and neutropenia are a major cause of morbidity and mortality following cytotoxic chemotherapy, and there is a known correlation between neutropenia and the risk of infection. Hematopoietic growth factors have been used successfully in the prevention and treatment of nentropenia. There is evidence to suggest that use of rHuG-CSF before the onset of neutropenia allows patients to receive the maximum benefit; however, patients who do not receive rHuG-CSF prophylactically still benefit from the use of rHuG-CSF for the treatment of febrile neutropenia. These patients have an accelerated neutrophil recovery and a shorter duration of febrile neutropenia. These effects seem to translate into a significant reduction in the number of patients requiring prolonged hospitalization. This paper reviews the use of rHuG-CSF in the treatment of febrile neutropenia and describes how it is routinely used by hematologists and oncologists in non-clinical trial settings.
Asian Pacific Journal of Cancer Prevention, 2012
Introduction: Febrile neutropenia is a relatively frequent event in cancer patients treated with chemotherapy and improvement in absolute neutrophil count (ANC) has been linked directly to improved outcome. Evaluation of granulocyte colony stimulating factors (GCSFs) for treatment has shown reduced incidences of episodes of prolonged neutropenia and protracted hospitalization. To determine absolute neutrophil counts with GCSF in febrile neutropenic cancer patients admitted to a tertiary care centre and to co-relate the improvement in ANC with mortality and hospital discharge. Methods: A prospective cross sectional study was carried at an oncology ward at Aga Khan University hospital from January 2010 to June 2011. All adult patients who were admitted and treated with GCSF for chemotherapy induced febrile neutropenia were included. Multivariable regression was conducted to identify the factors related with poor outcomes. Results: A total of 131 patients with febrile neutropenia were identified with mean age of 43.2 (18-85) years, 79 (60%) being ≤50. Seventy-five (57%) had solid tumors and 56 (43%) hematological malignancies, including lymphoma. Fifty seven (43.5%) had an ANC less 100 cells/mm 3 , 34 (26%) one between100-300 cells/mm 3 and 40 (31%) an ANC greater than 300 cells/mm 3. Thirty (23%) patients showed ANC recovery in 1-3 days, and 74(56%) within 4-7 days. Thirteen (10%) patients showed no recovery. The overall mortality was 18 (13.7%) patients. The mean time for ANC recovery seen in hematological malignancies was 6.34 days whereas for solid tumors it was 4.88 days. Patients with ANC <100 cells/mm 3 were more likely to die than patients with ANC >300 cells/mm 3 by a factor of 4.3. Similarly patients >50 years of age were 2.7 times more likely to die than younger patients. Conclusion: Our study demonstrated that use of GCSF, in addition to intravenous antibiotics, in treatment of patients with chemotherapy induced febrile neutropenia accelerates neutrophil recovery, and shortens antibiotic therapy and hospitalization. We propose to risk classify the patients at the time of admission to evaluate the cost effectiveness of this approach in a resource constrained setup.
The colony-stimulating factors: use to prevent and treat neutropenia and its complications
Expert Opinion on Biological Therapy, 2004
The colony-stimulating factors (CSFs) represent the only biological response modifiers used in clinical practice to treat or prevent neutropenia. These pleiotropic cytokines are available in clinical practice as granulocyte CSF (G-CSF), granulocyte-macrophage CSF (GM-CSF) and pegylated G-CSF. Neutropenia and its complications, most importantly febrile neutropenia (FN), remain major and serious side effects of cancer chemotherapy. Several studies and meta-analyses have addressed the clinical applications of CSFs to treat or prevent neutropenia. Guidelines have been developed to foster the appropriate use of CSFs. This article reviews the nature and use of the CSFs, and summarises the critical studies and guidelines. A historical perspective briefly describes the discovery, synthesis and clinical use of CSFs. The major biological and pharmacological characteristics are highlighted. The clinical applications of the CSFs are reviewed, including primary FN prophylaxis, secondary FN prophylaxis, treatment of FN, support of dose-dense chemotherapy regimens, use in leukaemia and myelodysplastic syndromes, utility in stem cell transplantation, and use in elderly and paediatric patients. Finally, clinical efficacy data, as well as the economic impact of the CSFs, are discussed.
Cancer research, 1990
A Phase I study of bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was under taken in 21 patients with advanced malignancy or neutropenia. rhGM-CSF was administered once daily by i.v. bolus injection (0.3 to 3 Mg/kg/ day) or 2-h i.v. infusion (3 to 20 Mg/kg day) for 10 days. rhGM-CSF at all i.v. doses caused an immediate transient decrease in circulating neutrophils, cosinophils, and monocytes. By 6 h after rhGM-CSF, cir culating leukocyte levels were restored. Daily i.v. bolus dosing (0.3 to 3 itg/kg/day) did not elevate leukocyte levels except in one neutropenic patient. Daily 2-h i.v. infusions (10 to 20 ¿ig/kg/day)caused a dosedependent leukocytosis with increased levels of neutrophils (up to 4.3fold), eosinophils (up to 18-fold), and monocytes (up to 3.5-fold). Marrow aspirates showed increased proportions of promyelocytes and myelocytes during rhGM-CSF administration. Retreatment after 10 days without rhGM-CSF resulted in a more marked leukocytosis at doses a 10 Mg/ kg/day. Platelet levels decreased for the first 3 days and then increased during the first course of rhGM-CSF administration. Two patients with chronic lymphocytic leukemia had a transient reduction in lymphocytosis. Serum cholesterol and albumin levels decreased, and vitamin li,. levels increased during rhGM-CSF treatment. At doses of up to 15 ¿ig/kg/day, rhGM-CSF was relatively well tolerated by the patients, but adverse effects included bone pain, lethargy, fever, rash, and weight gain. A first dose reaction characterized by hypoxia and hypotension was identified at dose levels •¿ 1 ¿ig/kg. Dosing i.v. was less potent at inducing a leukocy tosis than previously observed for equivalent s.c. doses and was associated with a higher incidence of generalized rash and first dose reactions. The maximal tolerated dose of i.v. rhGM-CSF was 15 jig/kg/day. Phase II studies in which the desired effect is to raise leukocyte levels should be undertaken at rhGM-CSF doses of 3 to 15 Mg/kg/day.