Biological Effects of Pegfilgrastim on Circulating Neutrophils in Breast Cancer Patients Undergoing Dose-Dense Chemotherapy

Invernizzi, Rosangela; Grasso, Donatella; Travaglino, Erica; Benatti, C; Collovà, Elena; Manzoni, M.; Livraghi, Luca; Danova, Marco; Riccardi, Alberto

doi:10.1159/000164588

Cited by 10 publications

(9 citation statements)

References 71 publications

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“…The results of this meta-analysis are supported by a number of individual pegfilgrastim studies [82,83,84,85,86,87,88]. A fixed pegfilgrastim 6-mg dose provided sufficient neutrophilic support to patients with breast cancer or other malignancies receiving dose-dense chemotherapy regimens (typically using one dose of pegfilgrastim in each 2-week chemotherapy cycle) [83,84,85,86,88]. The use of pegfilgrastim or other G-CSF agents has also been shown to facilitate maintenance of chemotherapy dose intensity in elderly patients [89,90,91].…”

Section: Chemotherapy-induced Neutropenia Managementsupporting

confidence: 68%

“…In an analysis of several clinical trials using various G-CSF agents, maintenance of the planned relative dose intensity was associated with G-CSF use [8]. The results of this meta-analysis are supported by a number of individual pegfilgrastim studies [82,83,84,85,86,87,88]. A fixed pegfilgrastim 6-mg dose provided sufficient neutrophilic support to patients with breast cancer or other malignancies receiving dose-dense chemotherapy regimens (typically using one dose of pegfilgrastim in each 2-week chemotherapy cycle) [83,84,85,86,88].…”

Section: Chemotherapy-induced Neutropenia Managementmentioning

confidence: 78%

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Prevention of Chemotherapy-Induced Neutropenia with Pegfilgrastim: Pharmacokinetics and Patient Outcomes

2012

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Patients receiving cytotoxic chemotherapy are at risk for developing chemotherapy-induced neutropenia (CIN). Filgrastim, a recombinant granulocyte colony-stimulating factor (G-CSF) that stimulates the proliferation, differentiation and function of neutrophils, is approved for the prevention of CIN. To eliminate the burden of daily filgrastim injection, pegfilgrastim, a long-acting form of filgrastim, was developed by covalently attaching a 20-kDa polyethylene glycol molecule to filgrastim to increase molecular size and thus reduce renal elimination. Consequently, neutrophil-mediated clearance is the primary mechanism for pegfilgrastim elimination. Therefore, after a single pegfilgrastim injection following chemotherapy treatment, pegfilgrastim concentration is sustained during neutropenia and decreases with neutrophil recovery. Pegfilgrastim has received marketing authorization approval from many regions to reduce the incidence of CIN based on the similar efficacy and safety of a single injection of 6 mg of pegfilgrastim administered once per chemotherapy cycle and 10 to 11 daily injections of filgrastim at 5 µg/kg. The efficient self-regulating clearance of pegfilgrastim allows administration once per chemotherapy cycle, thereby providing a more convenient treatment regimen than filgrastim.

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Section: Chemotherapy-induced Neutropenia Managementsupporting

confidence: 68%

Section: Chemotherapy-induced Neutropenia Managementmentioning

confidence: 78%

Prevention of Chemotherapy-Induced Neutropenia with Pegfilgrastim: Pharmacokinetics and Patient Outcomes

2012

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“…A slight reduction in neutrophil ROS production was observed after treatment with all three forms of rG-CSF (47). Two other studies suggested that there could be changes in neutrophil chemotaxis with pegfilgrastim treatment, as evidenced by the observed abnormalities in actin polymerization in breast cancer patients undergoing chemotherapy and treated with pegfilgrastim (48, 49). However, it is not clear whether this effect was due to chemotherapy or to pegfilgrastim treatment, since decreased neutrophil chemotaxis, which is associated with defects in actin polymerization (48), has also been reported with chemotherapy alone (50).…”

Section: Discussionmentioning

confidence: 96%

Kinetics of Neutrophils in Mice Exposed to Radiation and/or Granulocyte Colony-Stimulating Factor Treatment

et al. 2013

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Astronauts have the potential to develop the hematopoietic syndrome as a result of exposure to radiation from a solar particle event (SPE) during exploration class missions. This syndrome is characterized by a reduction in the number of circulating blood cells (cytopenias). In the present study the effects of SPE-like proton and γ radiation on the kinetics of circulating neutrophils were evaluated during a one-month time period using mice as a model system. The results revealed that exposure to a 2 Gy dose of either SPE-like proton or γ radiation significantly decreased the number of circulating neutrophils, with two nadirs observed on day 4 and day 16 postirradiation. Low circulating neutrophil count (neutropenia) is particularly important because it can increase the risk of astronauts developing infections, which can compromise the success of the mission. Thus, two granulocyte colony-stimulating factors (G-CSFs), filgrastim and pegfilgrastim were evaluated as countermeasures for this endpoint. Both forms of G-CSF significantly increased neutrophil counts in irradiated mice, however, the effect of pegfilgrastim was more potent and lasted longer than filgrastim. Using the expression of CD11b, CD18 and the production of reactive oxygen species (ROS) as markers of neutrophil activation, it was determined that the neutrophils in the irradiated mice treated with pegfilgrastim were physiologically active. Thus, these results suggest that pegfilgrastim could be a potential countermeasure for the reduced number of circulating neutrophils in irradiated animals.

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“…In a dose-ranging pegfilgrastim study in breast cancer patients, it was demonstrated that the exposure to pegfilgrastim was lower in cycle 3 than in cycle 1; however, the ANC nadir improved and the duration of neutropenia decreased in cycle 2 and the subsequent cycles, suggesting an expansion of neutrophil and neutrophil precursors mass in the later cycles that results in an increase in drug clearance [9] . This suggestion was supported by Invernizzi et al [10] , who demonstrated not only an increase in ANC (evaluated on day 14 or later and immediately before next chemotherapy) but also an increase in immature myeloid cells in peripheral blood after the first chemotherapy cycle given with G-CSF support with a relatively constant level in the subsequent cycles. Without G-CSF support, no increase in the neutrophil count immediately before chemotherapy occurs; the count was the lowest around 2 weeks after chemotherapy with return to baseline on day 1 of chemotherapy.…”

Section: Discussionmentioning

confidence: 63%

“…Without G-CSF support, no increase in the neutrophil count immediately before chemotherapy occurs; the count was the lowest around 2 weeks after chemotherapy with return to baseline on day 1 of chemotherapy. Also, progenitor cell apoptosis was significantly higher in case no pegfilgrastim support was given compared with pegfilgrastim support [10,11] . So, an increase in progenitor pool and a decrease in apoptosis could be one factor explaining the differences in blood cell counts between both treatment arms.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Recovery in Breast Cancer Patients Receiving Docetaxel-Containing Chemotherapy with and without Granulocyte Colony-Stimulating Factor Prophylaxis

et al. 2017

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Objective: The primary outcome of the current study is, whether there is a protective effect of prior chemotherapy or of prior granulocyte colony-stimulating factor (G-CSF) on the next cycle blood cell counts. Methods: Hematologic toxicity was evaluated, based on a randomized phase III study in breast cancer patients (n = 167) with >20% risk of febrile neutropenia. The primary endpoint was the nadir blood cell counts for patients treated with G-CSF given during all 6 chemotherapy cycles or limited to the first 2 chemotherapy cycles only. Results: For the present analyses, 47 patients were eligible. In the G-CSF 1-6 arm, the median white blood cell count (WBC) and absolute neutrophil count (ANC) nadir slowly decreased from 10.8 × 10⁹/L in cycle 1 to 7.5 × 10⁹/L in cycle 6 and from 7.1 × 10⁹/L to 5.5 × 10⁹/L, respectively. The median WBC nadir in the G-CSF 1-2 arm decreased from 1.2 × 10⁹/L in cycle 3 to 0.9 × 10⁹/L in cycle 6 and the ANC nadir showed a grade 4 neutropenia of 0.1 × 10⁹/L in cycles 3-6. All patients had ANC recovery to normal levels (≥1.5 × 10⁹/L) without delay on day 1 of the next cycle. Conclusion: We conclude that there is no protective effect of prior G-CSF or prior chemotherapy use on nadir blood cell counts in subsequent cycles.

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Biological Effects of Pegfilgrastim on Circulating Neutrophils in Breast Cancer Patients Undergoing Dose-Dense Chemotherapy

Cited by 10 publications

References 71 publications

Prevention of Chemotherapy-Induced Neutropenia with Pegfilgrastim: Pharmacokinetics and Patient Outcomes

Prevention of Chemotherapy-Induced Neutropenia with Pegfilgrastim: Pharmacokinetics and Patient Outcomes

Kinetics of Neutrophils in Mice Exposed to Radiation and/or Granulocyte Colony-Stimulating Factor Treatment

Neutrophil Recovery in Breast Cancer Patients Receiving Docetaxel-Containing Chemotherapy with and without Granulocyte Colony-Stimulating Factor Prophylaxis

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