Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis

Abstract

Background: Febrile neutropenia (FN) occurs following myelosuppressive chemotherapy and is associated with morbidity, mortality, costs, and chemotherapy reductions and delays. Granulocyte colony-stimulating factors (G-CSFs) stimulate neutrophil production and may reduce FN incidence when given prophylactically following chemotherapy.

Methods: A systematic review and meta-analysis assessed the effectiveness of G-CSFs (pegfilgrastim, filgrastim or lenograstim) in reducing FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. G-CSFs were compared with no primary G-CSF prophylaxis and with one another. Nine databases were searched in December 2009. Meta-analysis used a random effects model due to heterogeneity.

Results: Twenty studies compared primary G-CSF prophylaxis with no primary G-CSF prophylaxis: five studies of pegfilgrastim; ten of filgrastim; and five of lenograstim. All three G-CSFs significantly reduced FN incidence, with relative risks of 0.30 (95% CI: 0.14 to 0.65) for pegfilgrastim, 0.57 (95% CI: 0.48 to 0.69) for filgrastim, and 0.62 (95% CI: 0.44 to 0.88) for lenograstim. Overall, the relative risk of FN for any primary G-CSF prophylaxis versus no primary G-CSF prophylaxis was 0.51 (95% CI: 0.41 to 0.62). In terms of comparisons between different G-CSFs, five studies compared pegfilgrastim with filgrastim. FN incidence was significantly lower for pegfilgrastim than filgrastim, with a relative risk of 0.66 (95% CI: 0.44 to 0.98).

Conclusions: Primary prophylaxis with G-CSFs significantly reduces FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. Pegfilgrastim reduces FN incidence to a significantly greater extent than filgrastim.

Figure 1

Flow chart for identification of relevant studies.

Figure 2

Primary G-CSFs versus no primary G-CSF: FN incidence. Cancer types for each study are shown after the author and date. CHOP and CNOP = chemotherapy regimens for NHL (see Table 1 footnote); NHL = non-Hodgkin's lymphoma; SCLC = small-cell lung cancer; solid = solid tumours. *Indicates studies in patients aged ≥ 60 or ≥ 65 years.

Figure 3

Pegfilgrastim versus filgrastim: FN incidence. Cancer types for each study are shown after the author and date. HL = Hodgkin's lymphoma; NHL = non-Hodgkin's lymphoma. *Indicates studies in patients aged ≥ 60 or ≥ 65 years. In the Holmes 2002 (phase II) study,[37] FN incidence in the filgrastim arm was reported as 2/25, which was incorrectly converted to 12%. The absolute numbers (2/25) have been used in this analysis. Therefore the resulting relative risk differs slightly from that reported in the previous systematic review by Pinto (2007),[19] which used the 12% figure.