Kuderer, N.M. (2011). Meta-analysis of randomized controlled trials of granulocyte colony-stimulating factor prophylaxis in adult cancer patients receiving chemotherapy. Cancer Treatment and Research, 157, 127–143.

The primary purpose of this study was to determine the percentage of patients experiencing febrile neutropenia. A secondary goal was to examine infection-related mortality, all early mortality during chemotherapy, bone pain or musculoskeletal pain, and relative dose intensity.

Medline, EMBASE, Cancerlit, Cochrane, Database of Systematic Reviews,and Cochrane Central Register of Controlled Trials database were reviewed.

Key words include G-CSF, granulocyte–colony-stimulating factor, colony-stimulating factors (CSFs), recombinant G-CSF, lenograstim, filgrastim, pegfilgrastim, and pegylated filgrastim, randomized controlled trials

Inclusion criteria was primary and secondary G-CSF prophylaxis   

Studies were excluded if they encompassed those with granulocyte macrophage–colony-stimulating factor (GM-CSF), RCTs in children, leukemia or multiple myeloma, bone marrow or peripheral blood stem cell transplantation, and studies of established neutropenia or febrile neutropenia.
 

12,128 potentially relevant papers were reviewed.

Cochran’s Q statistic and inconsistency index of Higgins,fixed-effects model, and random effects models.

The Jadad scale was used to evaluate study quality.

17 randomized, controlled trials (RCTs) were included.

The total sample size was 3,493 patients  

The sample across all studies ranged from 31–928

Key characteristics included filgrastim in 10 trials (59%), lenograstim in six trials (35%), and pegfilgrastim in one trial (6%). Eleven trials (65%) involved patients with solid tumors and six (35%) were in patients with lymphoma, including four (24%) limited to older adult patients, eight studies using placebo control, and three that permitted secondary G-CSF in control patients (two prohibited its use and the remaining studies did not specify). Five RCTs prohibited the use of prophylactic antibiotics and three used antibiotic prophylaxis. The remaining did not specify.

Active treatment

Reductions in infection-related and early mortality with G-CSF were seen in patients with solid tumors but not among those with lymphoma.

This analysis and review confirms that primary prophylaxis with G-CSF significantly reduces the risk of febrile neutropenia while sustaining and enhancing chemotherapy dose delivery in patients receiving conventional chemotherapy across a broad range of baseline risk in eligible trials. The most important and previously unreported observation that emerged from this overview is the observed reduction in infection-related (RR = 0.552, p = 0.018) and all-cause (RR = 0.599, p = 0.002) early mortality in patients randomized to receive primary prophylaxis with G-CSF. There were no differences based on whether or not patients also received prophylactic antibiotics or between those receiving G-CSF as primary or secondary prophylaxis. 

• Early mortality was not defined in this analysis.
• Although methods for determination of heterogeneity were discussed, findings regarding heterogeneity were not reported.