The impact of primary prophylaxis with granulocyte colony-stimulating factors on febrile neutropenia during chemotherapy: a systematic review and meta-analysis of randomized controlled trials

Abstract

PurposeThe study aims to assess the relative efficacy of granulocyte colony-stimulating factor (G-CSF) products administered as primary prophylaxis (PP) to patients with cancer receiving myelosuppressive chemotherapy.MethodsA systematic literature review identified publications (January 1990 to September 2013) of randomized controlled trials evaluating PP with filgrastim, pegfilgrastim, lenograstim, or lipegfilgrastim in adults receiving myelosuppressive chemotherapy for solid tumors or non-Hodgkin lymphoma. Direct, indirect, and mixed-treatment comparison (MTC) were used to estimate the odds ratio and 95 % credible interval of febrile neutropenia (FN) during cycle 1 and all cycles of chemotherapy combined without adjusting for differences in relative dose intensity (RDI) between study treatment arms.ResultsTwenty-seven publications representing 30 randomized controlled trials were included. Using MTC over all chemotherapy cycles, PP with filgrastim, pegfilgrastim, lenograstim, and lipegfilgrastim versus no G-CSF PP or placebo were associated with statistically significantly reduced FN risk. FN risk was also significantly reduced with pegfilgrastim PP versus filgrastim PP. Over all chemotherapy cycles, there was a numerical but statistically nonsignificant increase in the FN risk for lipegfilgrastim PP versus pegfilgrastim PP. Using MTC in cycle 1, PP with filgrastim, pegfilgrastim, and lipegfilgrastim versus no G-CSF PP or placebo were associated with statistically significantly reduced FN risk.ConclusionsIn this meta-analysis, using MTC without adjustment for RDI, PP with all G-CSFs evaluated reduced the FN risk in patients receiving myelosuppressive chemotherapy. Future studies are needed to assess the influence of RDI on FN outcomes and to eliminate potential bias between G-CSF arms receiving more intensive chemotherapy than control arms.Electronic supplementary materialThe online version of this article (doi:10.1007/s00520-015-2686-9) contains supplementary material, which is available to authorized users.

The Effectiveness of Febrile Neutropenia Prophylaxis with Lipegfilgrastim in Routine Clinical Practice

“…It is important to realize that the risk of CHT regimen (in relation to CHT-induced neutropenia) is not the only criterion of G-CSF administration in the prevention of FN. Other very important factors are patient's condition (such as age, comorbidities, performance status) and the mutual cooperation between the patient and doctor (good compliance) (5,19,20). The discussed results proved that the prophylactic administration of lipegfilgrastim can almost eliminate the risk of FN and significantly reduce the risk of CHT dose reduction in the routine clinical practice in cases of a clear high-risk chemotherapy regimen or, in the presence of risk factors (such as age, comorbidities, performance status etc.…”

Granulocyte growth factor use in elderly patients with non-Hodgkin’s lymphoma in the United States: adherence to guidelines and comparative effectiveness

“…Granulocyte growth factors have been shown to be effective in reducing the depth and duration of chemotherapy-induced neutropenia as well as the risks of fever and infection during neutropenia [15]. Despite continuing controversy about which patients' risks of fever and infection justify the expense of these agents, primary prophylaxis with these agents is now recommended for all elderly patients with non-Hodgkin's lymphoma who undergo CHOP-based chemotherapy by professional societies in Europe [20,21] and the USA [22,23].…”

“…These outcomes lead to reduced dose intensity and effectiveness of chemotherapy [11,12]. Clinical trials have shown that administration of prophylactic granulocyte colony-stimulating factors (G-CSFs) improves relative dose intensity and reduces the rate of neutropenic infection in this population [13][14][15]. These findings, published a decade ago, led to specific recommendations from ASCO and NCCN for prophylactic use of G-CSFs among elderly patients receiving doxorubicin-based chemotherapy [16,17].…”

Revisão sistemática e análise de custo- minimização de lipegfilgrastim na profilaxia da neutropenia e da neutropenia febril relacionadas à quimioterapia citotóxica

“…Os comparadores incluídos foram pegfilgrastim (Bond et al, 2015, Bondarenko et al, 2013, Buchner et al, 2014, Volovat et al, 2015, Wang et al, 2015 e filgrastim (Bond et al, 2015, Wang et al, 2015, ambos com administração subcutânea, e assumiu-se eficácia não inferior entre os comparadores.…”

“…Diversos G-CSFs foram avaliados conforme descrito na Tabela 4. A revisão realizada por Wang et al, por meio das metanálises, confirmou o benefício das terapias G-CSFs na redução de risco de NF em comparação a placebo e não utilizar a terapia (Wang et al, 2015). O estudo de Bond et al, por meio de uma metanálise indireta, comparou o lipegfilgrastim com o filgrastim (Bond et al, 2015).…”