Pegfilgrastim -- rational drug design for the management of chemotherapy-induced neutropenia.
Neutropenia is the most important dose-limiting toxicity of myelotoxic chemotherapy. Current guidelines recommend primary prophylactic use of granulocyte colony stimulating factor (G-CSF) with chemotherapy regimens associated with an incidence of febrile neutropenia (FN) of at least 40% and in patients at high risk of infections, such as the elderly. Using prophylactic G-CSF support, planned chemotherapy doses are administered on time more frequently. Pegfilgrastim is a rationally designed recombinant human G-CSF with a sustained duration of action. A once-per-cycle 6-mg fixed dose of pegfilgrastim reduced the duration of severe neutropenia and the incidence of FN as efficiently as daily filgrastim in standard or dose-dense chemotherapy regimens in young and elderly patients with breast cancer, non-small-cell lung cancer and lymphomas. The safety profile of onceper- cycle pegfilgrastim is comparable with that of daily filgrastim. In conclusion, a fixed-dose of pegfilgrastim given once per cycle is a suitable substitute for body weight-based daily dosing of G-CSF, an improvement which should be particularly beneficial for outpatients receiving myelotoxic chemotherapy.
Lüftner
Diana
D
Medizinische Klinik und Poliklinik II mit Schwerpunkt Onkologie und Hämatologie, Charité Campus Mitte, Berlin, Germany. diana.lueftner@charite.de
Possinger
Kurt
K
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015195:Drug Design; D064420:Drug-Related Side Effects and Adverse Reactions; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D009503:Neutropenia / Q000209:etiology* / Q000517:prevention & control*; D011092:Polyethylene Glycols; D017410:Practice Guidelines as Topic; D010818:Practice Patterns, Physicians'; D011994:Recombinant Proteins; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000069585:Filgrastim