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Meta-Analysis
. 2014 Oct 30;2014(10):CD003039.
doi: 10.1002/14651858.CD003039.pub2.

Colony-stimulating factors for chemotherapy-induced febrile neutropenia

Rahul Mhaskar  1 , Otavio Augusto Camara Clark, Gary Lyman, Tobias Engel Ayer Botrel, Luciano Morganti Paladini, Benjamin Djulbegovic
Affiliations
Meta-Analysis

Colony-stimulating factors for chemotherapy-induced febrile neutropenia

Rahul Mhaskar et al. Cochrane Database Syst Rev. .

Abstract

Background: Febrile neutropenia is a frequent adverse event experienced by people with cancer who are undergoing chemotherapy, and is a potentially life-threatening situation. The current treatment is supportive care plus antibiotics. Colony-stimulating factors (CSFs), such as granulocyte-CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF), are cytokines that stimulate and accelerate the production of one or more cell lines in the bone marrow. Clinical trials have addressed the question of whether the addition of a CSF to antibiotics could improve outcomes in individuals diagnosed with febrile neutropenia. However, the results of these trials are conflicting.

Objectives: To evaluate the safety and efficacy of adding G-CSF or GM-CSF to standard treatment (antibiotics) when treating chemotherapy-induced febrile neutropenia in individuals diagnosed with cancer.

Search methods: We conducted the search in March 2014 and covered the major electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and SCI. We contacted experts in hematology and oncology and also scanned the citations from the relevant articles.

Selection criteria: We searched for randomized controlled trials (RCTs) that compared CSF plus antibiotics versus antibiotics alone for the treatment of chemotherapy-induced febrile neutropenia in adults and children.

Data collection and analysis: We used the standard methodological procedures expected by The Cochrane Collaboration. We performed meta-analysis of the selected studies using Review Manager 5 software.

Main results: Fourteen RCTs (15 comparisons) including a total of 1553 participants addressing the role of CSF plus antibiotics in febrile neutropenia were included. Overall mortality was not improved by the use of CSF plus antibiotics versus antibiotics alone (hazard ratio (HR) 0.74 (95% confidence interval (CI) 0.47 to 1.16) P = 0.19; 13 RCTs; 1335 participants; low quality evidence). A similar finding was seen for infection-related mortality (HR 0.75 (95% CI 0.47 to 1.20) P = 0.23; 10 RCTs; 897 participants; low quality evidence). Individuals who received CSF plus antibiotics were less likely to be hospitalized for more than 10 days (risk ratio (RR) 0.65 (95% CI 0.44 to 0.95) P = 0.03; 8 RCTs; 1221 participants; low quality evidence) and had more number of participants with a more faster neutrophil recovery (RR 0.52 (95% CI 0.34 to 0.81) P = 0.004; 5 RCTs; 794 participants; moderate quality evidence) than those treated with antibiotics alone. Similarly, participants receiving CSF plus antibiotics had shorter duration of neutropenia (standardized mean difference (SMD) -1.70 (95% CI -2.65 to -0.76) P = 0.0004; 9 RCTs; 1135 participants; moderate quality evidence), faster recovery from fever (SMD -0.49 (95% CI -0.90 to -0.09) P value = 0.02; 9 RCTs; 966 participants; moderate quality evidence) and shorter duration of antibiotics use (SMD -1.50 (95% CI -2.83 to -0.18) P = 0.03; 3 RCTs; 457 participants; low quality evidence) compared with participants receiving antibiotics alone. We found no significant difference in the incidence of deep venous thromboembolism (RR 1.68 (95% CI 0.72 to 3.93) P = 0.23; 4 RCTs; 389 participants; low quality evidence) in individuals treated with CSF plus antibiotics compared with those treated with antibiotics alone. We found higher incidence of bone or joint pain or flu-like symptoms (RR 1.59 (95% CI 1.04 to 2.42) P = 0.03; 6 RCTs; 622 participants; low quality evidence) in individuals treated with CSF plus antibiotics compared with those treated with antibiotics alone. Overall, the methodological quality of studies was moderate to low across different outcomes. The main reasons to downgrade the quality of evidence were inconsistency across the included studies and imprecision of results.

Authors' conclusions: The use of a CSF plus antibiotics in individuals with chemotherapy-induced febrile neutropenia had no effect on overall mortality, but reduced the amount of time participants spent in hospital and improved their ability to achieve neutrophil recovery. It was not clear whether CSF plus antibiotics had an effect on infection-related mortality. Participants receiving CSFs had shorter duration of neutropenia, faster recovery from fever and shorter duration of antibiotics use.

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Conflict of interest statement

OACC ‐ None known BD ‐ None known TEAB ‐ None known GL ‐ PI on research grant to the Fred Hutchinson Cancer Research Center, Seattle, WA, USA RM ‐ None known LMP ‐ None known

Figures

1
1
Study flow diagram.
2
2
1.1
1.1. Analysis
Comparison 1: Benefits and harms ‐ CSF + antibiotics vs antibiotics alone, Outcome 1: Overall mortality
1.2
1.2. Analysis
Comparison 1: Benefits and harms ‐ CSF + antibiotics vs antibiotics alone, Outcome 2: Infection related mortality
1.3
1.3. Analysis
Comparison 1: Benefits and harms ‐ CSF + antibiotics vs antibiotics alone, Outcome 3: Patients with hospitalization for greater than10 days
1.4
1.4. Analysis
Comparison 1: Benefits and harms ‐ CSF + antibiotics vs antibiotics alone, Outcome 4: Time to neutrophil recovery
1.5
1.5. Analysis
Comparison 1: Benefits and harms ‐ CSF + antibiotics vs antibiotics alone, Outcome 5: Duration of grade IV neutropenia
1.6
1.6. Analysis
Comparison 1: Benefits and harms ‐ CSF + antibiotics vs antibiotics alone, Outcome 6: Time to recovering from fever
1.7
1.7. Analysis
Comparison 1: Benefits and harms ‐ CSF + antibiotics vs antibiotics alone, Outcome 7: Time to withdrawal from antibiotics
1.8
1.8. Analysis
Comparison 1: Benefits and harms ‐ CSF + antibiotics vs antibiotics alone, Outcome 8: Deep vein thrombosis
1.9
1.9. Analysis
Comparison 1: Benefits and harms ‐ CSF + antibiotics vs antibiotics alone, Outcome 9: Bone and joint pain or flu‐like symptoms
2.1
2.1. Analysis
Comparison 2: Subgroup analysis ‐ Study population (children vs. adults), Outcome 1: Patients with hospitalization for greater than10 days
2.2
2.2. Analysis
Comparison 2: Subgroup analysis ‐ Study population (children vs. adults), Outcome 2: Time to neutrophil recovery
2.3
2.3. Analysis
Comparison 2: Subgroup analysis ‐ Study population (children vs. adults), Outcome 3: Duration of grade IV neutropenia
2.4
2.4. Analysis
Comparison 2: Subgroup analysis ‐ Study population (children vs. adults), Outcome 4: Time to recovering from fever
3.1
3.1. Analysis
Comparison 3: Subgroup analysis ‐ Type of CSF (G‐CSF vs. GM‐CSF), Outcome 1: Patients with hospitalization for greater than 10 days
3.2
3.2. Analysis
Comparison 3: Subgroup analysis ‐ Type of CSF (G‐CSF vs. GM‐CSF), Outcome 2: Time to neutrophil recovery
3.3
3.3. Analysis
Comparison 3: Subgroup analysis ‐ Type of CSF (G‐CSF vs. GM‐CSF), Outcome 3: Duration of grade IV neutropenia
3.4
3.4. Analysis
Comparison 3: Subgroup analysis ‐ Type of CSF (G‐CSF vs. GM‐CSF), Outcome 4: Time to recovering from fever
3.5
3.5. Analysis
Comparison 3: Subgroup analysis ‐ Type of CSF (G‐CSF vs. GM‐CSF), Outcome 5: Time to withdrawal from antibiotics
4.1
4.1. Analysis
Comparison 4: Subgroup analysis ‐ Hospital discharge criteria (fever resolution), Outcome 1: Patients with hospitalization for greater than 10 days
4.2
4.2. Analysis
Comparison 4: Subgroup analysis ‐ Hospital discharge criteria (fever resolution), Outcome 2: Time to neutrophil recovery
4.3
4.3. Analysis
Comparison 4: Subgroup analysis ‐ Hospital discharge criteria (fever resolution), Outcome 3: Duration of grade IV neutropenia
4.4
4.4. Analysis
Comparison 4: Subgroup analysis ‐ Hospital discharge criteria (fever resolution), Outcome 4: Time to recovering from fever
5.1
5.1. Analysis
Comparison 5: Subgroup analysis ‐ Type of malignancy, Outcome 1: Patients with hospitalisation for greater than10 days
5.2
5.2. Analysis
Comparison 5: Subgroup analysis ‐ Type of malignancy, Outcome 2: Time to neutrophil recovery
5.3
5.3. Analysis
Comparison 5: Subgroup analysis ‐ Type of malignancy, Outcome 3: Duration of grade IV neutropenia
5.4
5.4. Analysis
Comparison 5: Subgroup analysis ‐ Type of malignancy, Outcome 4: Time to recovering from fever
5.5
5.5. Analysis
Comparison 5: Subgroup analysis ‐ Type of malignancy, Outcome 5: Overall mortality
6.1
6.1. Analysis
Comparison 6: Sensitivity analysis ‐ Patients hospitalized for more than 10 days by allocation concealment and blinding, Outcome 1: Adequacy of allocation concealment
6.2
6.2. Analysis
Comparison 6: Sensitivity analysis ‐ Patients hospitalized for more than 10 days by allocation concealment and blinding, Outcome 2: Blinding
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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