Prophylactic G-CSF associated with reduced risk of febrile neutropenia and early death in adult patients with cancer who are receiving chemotherapy

Key Points

The use of prophylactic granulocyte colony-stimulating factors (G-CSF) in adult patients with cancer who are receiving chemotherapy is associated with a reduced risk of early death and febrile neutropenia, according to a systematic review and meta-analysis published in the Journal of Clinical Oncology.

The analysis included 17 randomized controlled trials of patients (N=3,493) with solid tumor (11 trials) or malignant lymphoma (6 trials) who received primary prophylactic G-CSF or placebo or who were included in untreated control groups. Trials that allowed the use of prophylactic antibiotics were included, provided that use was allowed equally in both study arms. Studies of children or of patients with leukemia or multiple myeloma and studies that included the use of granulocyte-macrophage colony-stimulating factor were excluded, as were those that included bone marrow or peripheral-blood stem-cell transplantation or that represented an economic analysis. Studies in which patients received dose-dense or dose-escalation chemotherapy or G-CSF for established neutropenia or febrile neutropenia and studies that allowed variances in drugs, doses, or chemotherapy or G-CSF schedules in different study arms were also excluded.

In all included studies, G-CSF was initiated 1 to 3 days after myelosuppressive chemotherapy was completed in each cycle. The G-CSF included in the trials were filgrastim (10 trials), lenograstim (6 trials), and pegfilgrastim (1 trial). The primary outcome was the proportion of patients with febrile neutropenia. The risk of infection-related mortality, early mortality (all-cause mortality during chemotherapy period), and bone and musculoskeletal pain were also analyzed.

FEBRILE NEUTROPENIA

A total of 3,182 patients were included in trials that reported febrile neutropia as an outcome. In total, 22.4% of patients receiving G-CSF vs 39.5% of control patients were diagnosed at least once with febrile neutropenia, representing a 46% RR reduction with use of G-CSF (weighted summary RR=0.54; 95% CI, 0.43–0.67; P<.0001). Pegfilgrastim was associated with significantly greater efficacy compared with filgrastim and lenograstim (RR=.08; 95% CI, 0.03–0.18; P<.0001). There were no significant efficacy differences between filgrastim and lenograstim.

Use of G-CSF was associated with significant reductions in the risk of febrile neutropenia in subgroup analyses of patients with lymphoma (RR=0.71; 95% CI, 0.59–0.85; P<.001) and patients with solid tumors (RR=0.44; 95% CI, 0.30–0.65; P<.001) and in studies that allowed the use of prophylactic antibiotics (RR=0.49; 95% CI, 0.33–0.72; P<.001).

INFECTION-RELATED MORTALITY

A total of 2,917 patients were included in trials that reported infection-related mortality as an outcome. In total, 1.5% of patients who received G-CSF vs 2.8% of control patients experienced infection-related mortality, representing a 45% RR reduction with use of G-CSF (weighted summary RR=0.55; 95% CI, 0.34–0.90; P=.018). The use of filgrastim was associated with reductions in infection-related mortality (RR=0.53; 95% CI, 0.30–0.92; P=.024) compared with control, but statistically significant reductions were not achieved with the use of lenograstim or pegfilgrastim.

EARLY MORTALITY

A total of 3,122 patients were included in trials that reported early mortality as an oucome. In total, 3.4% of patients who received G-CSF vs 5.7% of control patients experienced early mortality, representing a 40% RR reduction with use of G-CSF (weighted summary RR=0.60; 95% CI, 0.43–0.83; P=.002). The use of filgrastim and pegfilgrastim was associated with reductions in early mortality (RR=0.60; 95% CI, 0.41–0.89; P=.010 and RR=0.36; 95% CI, 0.13–0.99; P=.047, respectively) compared with control; statistically significant reductions were not achieved with lenograstim.

Use of G-CSF was associated with significant reductions in the risk of early mortality in a subgroup analysis of patients with solid tumors (RR=0.55; 95% CI, 0.37–0.84; P=.005) but not in a subgroup analysis of patients with lymphoma.

BONE AND MUSCULOSKELETAL PAIN

A total of 3,029 patients were included in trials that reported bone and musculoskeletal pain as an outcome. In total, 19.6% of patients who received G-CSF vs 10.4% of control patients experienced bone or musculoskeletal pain during the chemotherapy period (RR=4.02; 95% CI, 2.16–7.52; P<.0001).

The authors stated that this study further supports the theory that treatment with G-CSF reduces the risk of febrile neutropenia in this patient population and stated that this is the first report of significant risk reductions for infection-related and early mortality with the use of G-CSF.

SOURCE

Kuderer NM, Dale DC, Crawford J, Lyman GH. Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: A systematic review. J Clin Oncol. 2007;25:3158–3167.