Affiliation:
1. Ricardo Fernandes, Mohamed F.K. Ibrahim, Shaan Dudani, Kirstin Perdrizet, Habeeb Majeed, and Risa Shorr, The Ottawa Hospital; Ricardo Fernandes, Shaan Dudani, Kirstin Perdrizet, Habeeb Majeed, Brian Hutton, Dean Fergusson, and Mark Clemons, University of Ottawa; Sasha Mazzarello, Carol Stober, Lisa Vandermeer, Brian Hutton, Dean Fergusson, and Mark Clemons, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; and Bishal Gyawali, Nobel Hospital, Sinamangal, Kathmandu, Nepal.
Abstract
Purpose Despite 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. Methods Embase, 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. Results Of 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. Conclusion Primary 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.
Publisher
American Society of Clinical Oncology (ASCO)