Once-per-cycle pegfilgrastim (Neulasta) for the management of chemotherapy-induced neutropenia
Section snippets
Pegfilgrastim: rationale and molecular characteristics
Filgrastim was approved in 1991 to decrease the incidence of infection and febrile neutropenia (FN) in patients with nonmyeloid malignancies treated with myelosuppressive chemotherapy. Since that time, several million patients treated with chemotherapy for cancer have benefited from it. The availability of filgrastim markedly changed the treatment of patients with cancer, for whom the prevailing attitude had been the acceptance of treatment with potentially life-threatening toxicity. Filgrastim
Phase I studies in healthy volunteers and patients with cancer
The pharmacokinetics of pegfilgrastim given by the subcutaneous route have been studied both in healthy adult volunteers and in adult patients with cancer.5, 12 In 32 adult volunteers, pegfilgrastim administered as a single subcutaneous dose ranging from 30 to 300 μg/kg was well tolerated and produced dose-dependent increases in the absolute neutrophil count (ANC).5 The neutrophil counts increased from the pretreatment value in a dose- and time-dependent fashion, producing median peak values of
Conclusion
The commercial availability of pegfilgrastim, a newer colony-stimulating factor with a sustained duration of action, is an advance in neutrophil growth factors. Pegfilgrastim was created by the covalent attachment of a PEG molecule to the filgrastim parent protein in a process known as pegylation. Unlike filgrastim, which undergoes predominantly renal elimination, pegfilgrastim is of sufficient size to minimize renal elimination. Data in patients with cancer show that the primary route of
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Cited by (61)
Chemotherapy-induced neutropenia and emerging agents for prevention and treatment: A review
2022, Cancer Treatment ReviewsCitation Excerpt :PEGylation, which increases the size of the molecule and prevents renal excretion, has been most successful [42]. PEGylation increases the serum half-life of G-CSF by up to 42 h, enabling the dosing schedule to be 1 dose per cycle [43]. The first PEGylated G-CSF agent approved for use was pegfilgrastim in 2002 [44].
Polymer-drug conjugates: Design principles, emerging synthetic strategies and clinical overview
2022, International Journal of PharmaceuticsNanomedicines accessible in the market for clinical interventions
2021, Journal of Controlled ReleaseCitation Excerpt :It was synthesized by PEGylation of parent recombinant protein molecule NEUPOGEN® (Filgrastim) [87]. It is indicated for the treatment of febrile neutropenic patients who underwent myelosuppressive chemotherapy for non-myeloid malignancies [145]. Neulasta® is produced by covalent interaction of PEG with filgrastim, which is a recombinant human Granulocyte-colony stimulating factor (G-CSF) produced from E. coli that leads to a bulky molecule.
Side effects of using granulocyte-colony stimulating factors as prophylaxis of febrile neutropenia in cancer patients: A systematic review
2021, Critical Reviews in Oncology/HematologyCitation Excerpt :Even if the real prevalence of bone pain due to G-CSF is difficult to assess, given the difference in chemotherapy and G-CSF used, overall it could be estimated to range between 25 % and 38 % (Lambertini et al., 2014). This type of pain is generally described as mild or moderate (Biganzoli et al., 2004; Frampton and Keating, 2005; Aapro et al., 2010b; Renwick et al., 2009; Crawford, 2003; Jakubowski and Gabrilove, 1996), involving mainly the sternal, lumbosacral and sacroiliac regions (Van Ryckeghem et al., 2019) and it usually does not lead to the interruption of treatment with G-CSF (Biganzoli et al., 2004). Short-term bone pain is the most frequent adverse effect also in the pediatric setting.
Emergency granulopoiesis promotes neutrophil-dendritic cell encounters that prevent mouse lung allograft acceptance
2011, BloodCitation Excerpt :Accordingly, in our present studies, G-CSF was administered as a single bolus at the time of transplantation to better model the kinetics of G-CSF expression in Ext CI lung recipients. In contrast, when G-CSF is used to mobilize hematopoietic progenitors, it is generally given over the course of up to 5 days or it is PEGylated to increase stability, potentiating prolonged exposure to T cells within the blood and BM.35,36 Therefore, it remains likely that during lung transplantation, direct G-CSF exposure to T cells is relatively transient compared with its use as an agent to promote hematopoietic progenitor isolation.
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Dr Crawford receives grant or research support from, is a consultant to, and is on the speakers bureau of Amgen.