Renner, P., Milazzo, S., Liu, J.P., Zwahlen, M., Birkmann, J., & Horneber, M. (2012). Primary prophylactic colony-stimulating factors for the prevention of chemotherapy-induced febrile neutropenia in breast cancer patients. Cochrane Database of Systematic Reviews, 10, CD007913.

The purpose of this meta-analysis and systematic review was to examine the effects of prophylactic colony-stimulating factors (CSFs) related to reduction in incidence and duration of febrile neutropenia as well as “all-cause” and infection-related mortality in patients with breast cancer undergoing chemotherapy.

Various national and international databases were examined.

Articles were examined if they were randomized, controlled trials (RCTs) comparing CSFs with placebo or no treatment for patients with breast cancer and all stages identified as at-risk for developing febrile neutropenia during chemotherapy

Articles were excluded if they reported on trials for secondary prophylaxis with G-CSF or GM-CSF or primary prophylaxis with G-CSF.

1,023 total references were retrieved

Quality of the evidence was evaluated using the guidelines from the Cochrane Handbook for Systematic Reviews of Interventions for risk of bias. The GRADES levels of evidence were applied to study outcome areas.

• Eight studies were included in the final analysis.
• The sample range across all eight studies was 20–928
• Patients were aged 18-78 years, with a mean age of 50. 
• Patients had a diagnosis of breast cancer and were receiving chemotherapy (any regimen).

• The phase of care was active antitumor treatment  
• Application was for elder care

Effect of primary prophylactic CSF use on rate of febrile neutropenia showed a risk ratio (RR) of 0.27 (95% CI [0.11, 0.7]) in favor of CSF prophylaxis. Evidence in this area was graded as moderate.
Early mortality risk was significantly lower in the intervention group (RR = 0.32; 95% CI [0.13, 0.77].  When one large study was taken out of analysis, accounting for five deaths in the control course and 14 in the control group, the significance was not realized (RR = 0.19; 95% CI [0.03, 1.24]) The grade of evidence in this area was deemed to be low. There was minimal size of effect on the outcome of rate of infection related mortality with (RR = 0.14; 95% CI [0.02, 1.20]). Evidence in this area was graded as low.

Conclusions are difficult to summarize because the studies did not use standard definition of febrile neutropenia, subjects were not homogenous for breast cancer (stage, pathology, treatment, and risk for FN).
No recommendations can be made based on quality and limitations of studies.

Six of the studies identified risk of bias, three of these six had more than one bias risk.  Forty percent of patients included in summary are from one study. Overall, studies were of low to only moderate level of quality. This review includes only studies conducted on patients with breast cancer.

This report does not strengthen evidence already available from guidelines for prophylactic use of CSFs in breast cancer.