Primary Febrile Neutropenia Prophylaxis for Patients Who Receive FEC-D Chemotherapy for Breast Cancer: A Systematic Review

Abstract

PurposeDespite widespread use of fluorouracil, epirubicin, cyclophosphamide, docetaxel (FEC-D) chemotherapy in breast cancer, the optimal strategy for primary febrile neutropenia (FN) prophylaxis remains unknown. A systematic review was therefore performed.MethodsEmbase, Ovid MEDLINE, PubMed, Cochrane Database of Systematic Reviews, Cochrane Register of Controlled Trials, and conference proceedings were searched from 1946 to April 2016 for trials that reported the effectiveness of primary FN prophylaxis with FEC-D chemotherapy. Outcome measures were incidence of FN; treatment-related hospitalizations; chemotherapy dose delays, reductions, and discontinuations; and adverse events from prophylaxis.ResultsOf 2,205 identified citations, eight studies (n = 1,250) met our eligibility criteria. Three additional studies (n = 293) were identified from a prior systematic review. Three randomized controlled trials (n = 576), one phase IV single-arm trial (n = 69), one prospective observational study (n = 37), and six retrospective studies (n = 861) were identified. Agents investigated were pegfilgrastim (n = 108), filgrastim (n = 1,119), and ciprofloxacin (n = 89). The heterogeneity of studies meant that a narrative synthesis of results was performed. Median FN rates for patients who received FEC-D with and without primary prophylaxis were 10.1% (interquartile range [IQR], 3.9% to 22.6%) and 23.9% (IQR, 9.2% to 27.3%), respectively. In the absence of primary prophylaxis, FN was more common during docetaxel than during FEC. Data from six studies showed a median rate of dose reductions and delays of 6.1% (IQR, 3.1% to 14.3%) and 19.3% (IQR, 10.5% to 32.8%), respectively, that occurred as a consequence of FN. Toxicity from prophylaxis itself was rarely reported.ConclusionPrimary FN prophylaxis is effective in patients who receive FEC-D chemotherapy. The paucity of prospective data makes optimal recommendations about the choice and timing of prophylaxis challenging.

Is PEGylated G-CSF superior to G-CSF in patients with breast cancer receiving chemotherapy? A systematic review and meta-analysis

“…G-CSF-type therapeutic agents were widely used in the clinic to reduce CIN and were accepted in different clinical guidelines for patients receiving high FN chemotherapy regimens [8,9]. However, because of its primary clearance through the kidney, human G-CSF shows a short half-life, requiring daily administration intravenously or subcutaneously, which means patients suffer increased rates of injection site infection and display reduced tolerance [10,11]. To extend the half-life, polyethylene glycol (PEG) was introduced into G-CSF (PEGylated G-CSF), which changed the drugs' method of clearance, resulting in a decrease in the systemic clearance of the PEGylated form and a single dose showed efficacy comparable to that of daily injections of normal G-CSF [12,13].…”

A multi-centre study comparing granulocyte-colony stimulating factors to antibiotics for primary prophylaxis of docetaxel-cyclophosphamide induced febrile neutropenia

“…It is challenging to compare our findings with those in the literature, as past studies vary in the type of outcome they report (FN rates, neutropenia rates) and also in the type of analysis reported (by proportion of patients or per cycle of chemotherapy) [ [2] , [3] , [4] , 9 , 23 , [26] , [27] , [28] , [29] ]. As outcome events can be expressed by the rate in the study population overall, and by the total number of chemotherapy cycles received, we chose to present both formats [ 30 ]. With respect to study endpoints, TC is not an innocuous regimen even with G-CSF use, as 33.9% of G-CSF patients experienced at least one event related to the primary or secondary endpoint.…”

Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematologic malignancies and solid tumors: 2020 updated guidelines of the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (AGIHO/DGHO)

“…The modest benefit of antibacterial prophylaxis in MM patients has thus to be weighed carefully against the risk of resistance development, toxicity, and its impact on following therapies. Given the established quality of evidence, after thorough review of the identified literature, it was thus decided that the methodology of most new studies was insufficient to allow relevant new conclusions on prophylactic efficacy [ 55 , 89 – 96 ].…”