A systematic literature review of the efficacy, effectiveness, and safety of filgrastim

Dale, David C.; Crawford, Jeffrey; Klippel, Zandra; Reiner, Maureen; Osslund, Timothy D.; Fan, Ellen; Morrow, Phuong Khanh; Allcott, Kim; Lyman, Gary H.

doi:10.1007/s00520-017-3854-x

Cited by 70 publications

(50 citation statements)

References 52 publications

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“…Availability of the first recombinant human granulocyte-colony stimulating factor (rhG-CSF) in the 1990s (filgrastim) provided a safe and effective means to reduce the considerable burden of infection-related morbidity and mortality associated with chemotherapy-induced neutropenia (CIN). 1 The advent of pegfilgrastim, the first long-acting rhG-CSF, a decade later simplified supportive care for CIN with a once-per-chemotherapy-cycle option. 2 Since then, supportive care options for CIN have not changed other than through the introduction of biosimilar alternatives.…”

Section: Introductionmentioning

confidence: 99%

A comparison of eflapegrastim to pegfilgrastim in the management of chemotherapy‐induced neutropenia in patients with early‐stage breast cancer undergoing cytotoxic chemotherapy (RECOVER): A Phase 3 study

Cobb¹,

Moon

Mezei

et al. 2020

Cancer Medicine

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Eflapegrastim (Rolontis®) is a novel, long‐acting hematopoietic growth factor consisting of a recombinant human granulocyte‐colony stimulating factor (rhG‐CSF) analog conjugated to a human IgG4 Fc fragment via a short polyethylene glycol linker. We report results from a second pivotal, randomized, open‐label, Phase 3 study comparing the efficacy and safety of eflapegrastim to pegfilgrastim for reducing the risk of chemotherapy‐induced neutropenia. Patients with Stage I to IIIA early‐stage breast cancer (ESBC) were randomized 1:1 to fixed‐dose eflapegrastim 13.2 mg (3.6 mg G‐CSF) or pegfilgrastim (6 mg G‐CSF) administered one day after standard docetaxel/cyclophosphamide (TC) therapy for four cycles. The primary objective was to demonstrate noninferiority (NI) of eflapegrastim compared to pegfilgrastim in mean duration of severe neutropenia (DSN; Grade 4) in Cycle 1. A total of 237 eligible patients were randomized 1:1 to receive either eflapegrastim (n = 118) or pegfilgrastim (n = 119). Cycle 1 severe neutropenia was observed in 20.3% (n = 24) of patients receiving eflapegrastim and 23.5% (n = 28) receiving pegfilgrastim. The DSN of eflapegrastim in Cycle 1 was noninferior to pegfilgrastim with a mean difference of −0.074 days (NI P‐value < .0001). Noninferiority was maintained throughout the four treatment cycles (P < .0001 in all cycles). Other efficacy endpoints results were comparable between treatment arms, and adverse events, irrespective of causality and grade, were comparable between treatment arms. The results demonstrate noninferior efficacy and comparable safety for eflapegrastim, at a lower G‐CSF dose, vs pegfilgrastim. The potential for the increased potency of eflapegrastim to deliver improved clinical benefit warrants further clinical study.

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Section: Introductionmentioning

confidence: 99%

A comparison of eflapegrastim to pegfilgrastim in the management of chemotherapy‐induced neutropenia in patients with early‐stage breast cancer undergoing cytotoxic chemotherapy (RECOVER): A Phase 3 study

Cobb¹,

Moon

Mezei

et al. 2020

Cancer Medicine

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“…A recent meta‐analysis of nine randomised clinical trials including 2197 patients (filgrastim, n= 1130; placebo or no treatment, n = 1067) showed that the use of filgrastim led to a decrease in FN incidence (relative risk [RR] 0.63, 95% CI 0.53‐0.75), a result further confirmed in two observational studies . A meta‐analysis of five randomised clinical trials and one non‐randomised clinical trial with a total of 1409 patients (filgrastim, n = 714; placebo or no treatment, n = 695) reported a decreased incidence in grade 3/4 neutropenia with filgrastim (RR 0.50, 95% CI 0.37‐0.68) …”

Section: Discussionmentioning

confidence: 93%

“…The authors reported a reduction in the incidence of FN and in the number of G3‐4 neutropenia events, with a decreased duration of neutropenia in favour of patients treated with filgrastim. The use of G‐CSFs led to a decrease, albeit not significant, in the incidence of infections, use of antibiotic therapy and hospitalisation . In all of the above studies, patients receiving filgrastim showed better maintenance of the planned dose and better compliance with administration timing.…”

Section: Methodsmentioning

confidence: 90%

“…In a recent meta‐analysis, Dale et al assessed the efficacy of G‐CSFs in terms of FN incidence or G3‐4 neutropenia, duration of neutropenia, dose intensity of chemotherapy, incidence of infections, use of antibiotics, hospitalisation and OS . The authors reported a reduction in the incidence of FN and in the number of G3‐4 neutropenia events, with a decreased duration of neutropenia in favour of patients treated with filgrastim.…”

Section: Methodsmentioning

confidence: 99%

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Clinical role of filgrastim in the management of patients at risk of prolonged severe neutropenia: An evidence‐based review

et al. 2019

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Background: Patients undergoing chemotherapy are at risk of toxicity, especially of haematological origin. Granulocyte depletion, although often underestimated, can lead to the occurrence of an event defined as febrile neutropenia (FN). Neutropenic fever syndromes are dangerous because they cause major complications in around 25%-30% of patients and have a mortality rate of up to 11%. Treatment for FN was limited to antibiotics and supportive therapies until filgrastim was approved for use in the 1990s. Objectives:The present systematic review focuses on the efficacy and safety of this haematopoietic growth factor. Data Sources and Methods:For this review, a systematic literature search of electronic databases and references from recent reviews up to December 2018 was carried out to identify clinical trials, observational studies and case reports evaluating filgrastim efficacy and safety. English language was defined as a restriction.Published randomised controlled trials (RCTs), case reports and reviews analysing the effects of filgrastim on severe neutropenia and its limits were considered. Four review authors independently selected the studies, assessed the risk of bias and extracted study data. Results:As reported in ASCO guidelines, the efficacy of filgrastim with respect to placebo or no treatment in RCTs is based on its prevention of FN. A recent meta-analysis analysed nine RCTs with 2197 patients, revealing a reduction in the incidence of FN with filgrastim (risk ratio [RR] 0.63, 95% CI 0.53-0.75). These findings were further confirmed in two observational studies. Bone pain is the most commonly reported adverse event with filgrastim, while other toxicities are associated with filgrastim efficacy and with an increased neutrophil count. Key Findings:In conclusion, our findings attest to the previous results on the efficacy and safety of filgrastim.

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“…El r-met-hu G-CSF no glicosilado, conocido comercialmente como Filgrastim, ha sido utilizado con éxito para estimular la proliferación y la maduración de células hematopoyéticas (Dale et al, 2017). Sin embargo, el papel fisiológico del r-met-hu G-CSF en otros tejidos no hematopoyéticos, tales como el tejido testicular, así como su efecto en la proliferación y diferenciación de las células que lo componen es una incógnita.…”

Section: Introductcionunclassified

EFECTO DE LA APLICACIÓN DEL FACTOR ESTIMULANTE DE COLONIAS DE GRANULOCITOS RECOMBINANTE HUMANO (r-met-hu G-CSF) EN EL DESARROLLO SEXUAL DE CORDEROS PREPÚBERES

Gutierrez-Reinoso¹,

Aponte²,

Ilbay-Caguana³

et al. 2017

SPERMOVA

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The main objective of this study was to analyse the effects of r-met-hu G-CSF application as an inductor of early sexual development in prepubertal ram lambs. 20 Corriedale ram lambs (age= 2 months; ~18 kg l.w.) were divided in 4 groups: a control group (T1; n= 5) and 3 treated groups (T2, T3 and T4; n= 5 each) were administered a subcutaneous injection of r-met-hu G-CSF/Filgrastim daily for 4 consecutive days [(T2; 1 µg/kg l.w.; 18 µg/day; total= 72 µg), (T3; 10 µg/kg l.w.; 180 µg/day; total= 720 µg) y (T4; 20 µg/kg l.w.; 360 µg/day; total= 1.440 µg)]. A haematological analysis (white blood cells) was performed to determine the response of the spinal cord and confirm the hematopoietic effect of r-met-hu G-CSF. The testis weight, testicular morphometry and testicular volume were evaluated as well. To determine the effectiveness of the r-met-hu G-CSF treatment on sexual development, histological alterations (seminiferous tubules, Sertoli cells, gonocytes, spermatogonia, among others) were also evaluated as well as the endocrine response (FSH, LH, testosterone and cortisol) by ELISA. Significant differences were found in the number of leukocytes between the T4 vs. T1, T2 and T3 groups, from day 3 onwards (p<0.05). Lymphocyte percentage was significantly higher in T3 and T4 (p<0.05) compared to control (T1) and T2 from day 2 onwards. In addition, significant differences were observed in the testicular weight between the T1/T2 and the T3/T4 groups (p<0.05), as well as between the T1 and the T3/T4 regarding testicular volume (p<0.05). The hormone levels differed significantly in FSH concentration obtained in T3 compared to the other groups from day 3 onwards (p<0.05). Regarding LH and testosterone, significant differences were found between the T4 and the rest of the groups, which were evident from day 2 (LH) and day 3 (testosterone) (p<0.05). The cortisol did not differ among groups (p>0,05). With regard to histological alterations, T3 showed a more advanced cellular profile presenting primary spermatocytes, while T4 reached the generation of round spermatids. In conclusion, the application of r-met-hu G-CSF (Filgrastim) as a stimulating factor for early sexual development affected fast and positively the white blood cells´ haematopoiesis and the hormonal activity when applied at high concentrations, and accelerated the testicular development in prepubertal lambs, affecting not only endocrine hormone levels but also the testicular weight and volume, as well as the spermatogenic process.Keywords: r-met-hu G-CSF, testicular histopathology, sexual development, hormonal profile, ovine RESUMENEl principal objetivo del presente estudio fue analizar el efecto de la aplicación de r-met-hu G-CSF como inductor al desarrollo sexual temprano en corderos prepúberes. Se utilizaron 20 corderos de la raza Corriedale (edad: 2 meses; ~18 kg p.v.) divididos en 4 grupos: grupo control (T1; n= 5) y 3 grupos tratados (T2, T3 y T4; n= 5 cada uno) con una dosis diaria de r-met-hu G-CSF/Filgrastim durante 4 días consecutivos [(T2; 1...

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A systematic literature review of the efficacy, effectiveness, and safety of filgrastim

Cited by 70 publications

References 52 publications

A comparison of eflapegrastim to pegfilgrastim in the management of chemotherapy‐induced neutropenia in patients with early‐stage breast cancer undergoing cytotoxic chemotherapy (RECOVER): A Phase 3 study

A comparison of eflapegrastim to pegfilgrastim in the management of chemotherapy‐induced neutropenia in patients with early‐stage breast cancer undergoing cytotoxic chemotherapy (RECOVER): A Phase 3 study

Clinical role of filgrastim in the management of patients at risk of prolonged severe neutropenia: An evidence‐based review

EFECTO DE LA APLICACIÓN DEL FACTOR ESTIMULANTE DE COLONIAS DE GRANULOCITOS RECOMBINANTE HUMANO (r-met-hu G-CSF) EN EL DESARROLLO SEXUAL DE CORDEROS PREPÚBERES

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