Neutropenia is a serious hematologic toxicity of myelosuppressive
chemotherapy. The discovery that
granulocyte colony-stimulating factor (
G-CSF) could stimulate the production of neutrophils was followed by the purification and molecular cloning of
filgrastim (
Neupogen), the human recombinant form of the
protein, between 1984 and 1986. In this article, we review 20 years of clinical literature with
filgrastim and the more recent experience with
pegfilgrastim (
Neulasta) to support the delivery of
chemotherapy. The earliest clinical studies of
filgrastim showed that it produces immediate transient
leukopenia followed by a sustained, dose-dependent increase in circulating neutrophils. In the two registrational studies of
filgrastim, the cumulative incidence of
febrile neutropenia (FN) was reduced by about 50% compared with placebo. Subsequent clinical trials and meta-analyses established that primary prophylaxis with
filgrastim (beginning in the first cycle of
chemotherapy) reduced the incidence of FN, FN-related hospitalizations, intravenous anti-infective use,
infection-related mortality, and the need for
chemotherapy dose modification, compared with placebo or no treatment, in many
tumor types.
Pegfilgrastim, formed by the addition of a
polyethylene glycol molecule to
filgrastim, has comparable efficacy to
filgrastim when administered only once per
chemotherapy cycle. High-level evidence indicates that both
filgrastim and
pegfilgrastim improve the likelihood of completing dose-dense and dose-intense
chemotherapy. The most recent guidelines from three international
cancer organizations, the European Organization for Research and Treatment of
Cancer, the American Society of Clinical Oncology, and the US National Comprehensive
Cancer Network, are in agreement that
filgrastim or
pegfilgrastim should be given prophylactically when the risk of FN with a
chemotherapy regimen is > or =20%, or when the risk is 10-20% and the patient has other risk factors for FN. The development of
filgrastim and
pegfilgrastim has revolutionized oncology practice. Prophylactic use of these agents has enabled development of more aggressive
chemotherapy regimens, including dose-dense
chemotherapy, and treatment of a broader range of patients.