Optimal primary febrile neutropenia prophylaxis for patients receiving docetaxel-cyclophosphamide chemotherapy for breast cancer: a systematic review

Due to the high rate of febrile neutropenia (FN) with docetaxel-cyclophosphamide (DC) chemotherapy, primary FN prophylaxis is recommended. However, the optimal choice of prophylaxis [i.e., granulocyte-colony stimulating factors (G-CSF) or antibiotics] is unknown. A systematic review was performed to address this knowledge gap. Embase, Ovid Medline, Pubmed, the Cochrane database of systematic reviews, and Cochrane register of controlled trials were searched from 1946 to April 2016 for studies evaluating primary prophylactic FN treatments in breast cancer patients receiving DC chemotherapy. Outcome measures evaluated included: incidence of FN and treatment-related hospitalizations, chemotherapy dose reduction/delays/discontinuations, and adverse events. Screening and data collection were performed by two independent reviewers. Of 2105 identified records, 7 studies (n = 2535) met the pre-specified eligibility criteria. Seven additional studies (n = 621) were identified from prior systematic reviews. There were 3 randomized controlled trials (RCTs) (n = 2256) and 11 retrospective studies (n = 900). Study sample sizes ranged from 30 to 982 patients (median 99.5), evaluating pegfilgrastim (n = 1274), filgrastim (n = 1758), and oral ciprofloxacin (n = 108). Given the heterogeneity of patients and study design, a narrative synthesis of results was performed. Median FN rates with and without primary prophylaxis were 6.6 % (IQR 3.9-10.6 %) and 31.3 % (IQR 25-33 %), respectively. No FN-related deaths were reported. No RCT directly compared G-CSF with antibiotic interventions. Primary FN prophylaxis reduces the incidence of FN. Despite considerable cost and toxicity differences between G-CSF and antibiotics, there is insufficient data to make a recommendation of one strategy over another.