Use of filgrastim and pegfilgrastim to support delivery of chemotherapy: twenty years of clinical experience.
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.
Renwick
William
W
Department of Haematology and Medical Oncology, Western Hospital, Footscray, Melbourne, Victoria, Australia. william.renwick@mh.org.au
Pettengell
Ruth
R
Green
Michael
M
D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced* / Q000517:prevention & control*; D011092:Polyethylene Glycols; D011994:Recombinant Proteins
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000069585:Filgrastim