Colony stimulating factors for chemotherapy induced febrile neutropenia

Abstract

Background: Febrile neutropenia is a frequent event for cancer patients undergoing chemotherapy and it is potentially a life threatening situation. The current treatment is supportive care plus antibiotics. Colony stimulating factors (CSF) are cytokines that stimulate and accelerate the production of one or more cellular lines in bone marrow. Some clinical trials addressed the question of whether the addition of CSF to antibiotics (ATB) could improve the outcomes of patients with febrile neutropenia. The results of these trials are conflicting and no definitive conclusion could be reached.

Objectives: To evaluate the safety and effectiveness of adding colony stimulating factors to ATB when treating febrile neutropenia caused by cancer chemotherapy.

Search strategy: The search covered the major electronic databases: CANCERLIT, EMBASE, LILACS, MEDLINE, SCI and The Cochrane Controlled Trials Register. Experts were consulted and references from the relevant articles scanned.

Selection criteria: We looked for all randomized controlled trials (RCTs) that compare CSF plus antibiotics versus antibiotics alone for the treatment of established febrile neutropenia in adults and children.

Data collection and analysis: Two of the reviewers independently selected, critically appraised and extracted data from the studies. A meta-analysis of the select studies was performed, using Review Manager.

Main results: More than 8000 references were screened. Thirteen studies were included. The overall mortality was not influenced by the use of CSF [Odds Ratio (OR) = 0.68; 95% Confidence Interval (CI) = 0.43 to 1.08; p=0.1]. A marginally significant result was obtained for the use of CSF in reducing infection related mortality [OR= 0.51; 95% CI = 0.26 to 1.00; p=0.05], but this result was highly influenced by one study. When this study is excluded from our analysis, this possible benefit disappears [OR= 0.85; 95% CI = 0.33 to 2.20; p= 0.7]. The group of patients treated with CSF had a shorter length of hospitalization [Hazard Ratio (HR) = 0.63; 95% CI = 0.49 to 0.82; p=0.0006] and a shorter time to neutrophil recovery [HR= 0.32; 95% CI = 0.23 to 0.46; p < 0.00001].

Reviewer's conclusions: The use of CSF in patients with febrile neutropenia due to cancer chemotherapy does not affect overall mortality, but reduces the amount of time spent in hospital and the neutrophil recovery period. It was not clear whether CSF has an effect on infection-related mortality.