Febrile neutropenia is a frequently occurring complication following chemotherapy. It causes significant short-term morbidity, mortality, and is costly. It may also affect subsequent chemotherapy dosing, which in turn, could lead to inferior long-term survival.1 To reduce the incidence of febrile neutropenia and its complications, primary granulocyte-colony stimulating factor (G-CSF) prophylaxis is recommended by international guidelines when the risk of febrile neutropenia is 20% or higher.2 In daily practice, febrile neutropenia rates are based on data from randomised controlled trials, but observational studies consistently report higher incidences of febrile neutropenia.3
In this issue of the Netherlands Journal of Medicine, van Dooijeweert et al.4 describe that in a retrospective cohort of 181 breast cancer patients, the rate of febrile neutropenia following three cycles of 5-fluorouracil, epirubicin, cyclophosphamide (FEC) and three cycles of docetaxel (D) is significantly higher (31.5%) than the commonly assumed rate (10-20%) described in the European Organisation for Research and Treatment of Cancer guideline.5 The occurrence of febrile neutropenia was highest after the first docetaxel cycle (20.9%). The authors conclude that this high percentage of febrile neutropenia following docetaxel treatment justifies starting primary G-CSF prophylaxis during the first docetaxel cycle.
This conclusion adds to the existing literature on the incidence of febrile neutropenia after FEC-D and its prevention by primary G-CSF treatment, as the authors rightly mention. A recent systematic review, also cited by van Dooijeweert et al., summarizes 11 mostly retrospective studies on the rate of febrile neutropenia after FEC-D with and without primary G-CSF prophylaxis. This review concludes that patients who received FEC-D with and without primary prophylaxis, presented median febrile neutropenia rates of 10.1% and 23.9%, respectively.6
Although G-CSF clearly reduces the rate of febrile neutropenia after FEC-D, a remaining question is whether primary G-CSF prophylaxis after FEC-D is cost-effective, and whether preventing febrile neutropenia reduces long-term mortality. These studies are difficult to conduct, and will most likely not be performed anymore because FEC-D is less frequently used. Nonetheless, as is concluded by van Dooijeweert et al., the febrile neutropenia rate of more than 20% justifies, according to international guidelines, the use of primary G-CSF prophylaxis when FEC-D is given, in breast cancer patients in adjuvant and neo-adjuvant settings.