Michael Rader, MD

Neutropenia is the primary dose-limiting toxicity in patients treated with myelosuppressive chemotherapy, leading in some cases to substantial morbidity and early mortality, and disrupting treatment with potentially curative regimens. The use of granulocyte colony-stimulating factors (G-CSFs) such as filgrastim (Neupogen) and pegfilgrastim (Neulasta), as primary prophylaxis starting in the first cycle of chemotherapy, has been shown to reduce the rates of febrile neutropenia (FN) and of FN-related hospitalization, as well as the use of intravenous anti-infectives. A recent meta-analysis has shown significantly lower infection-related mortality with the first-cycle use of G-CSFs. Both filgrastim and pegfilgrastim were originally approved on the basis of their effectiveness in patients treated with chemotherapy regimens that are associated with a 40% or greater risk of FN. Pegfilgrastim, which is given once per cycle, has been shown to reduce the risk of FN by 94% in breast cancer patients treated with docetaxel (Taxotere). In addition, a recent cost-minimization analysis has shown that first-cycle use of pegfilgrastim may be cost-neutral in patients in whom the predicted risk of FN is less than 20%. These findings have important implications for clinical guidelines for preventing chemotherapy-induced neutropenia and FN.