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BMC Cancer May 2021Pegfilgrastim, a long-acting granulocyte colony-stimulating factor (G-CSF), is commonly used to prevent febrile neutropenia (FN), a potentially life-threatening...
Prophylactic pegfilgrastim to prevent febrile neutropenia among patients receiving biweekly (Q2W) chemotherapy regimens: a systematic review of efficacy, effectiveness and safety.
BACKGROUND
Pegfilgrastim, a long-acting granulocyte colony-stimulating factor (G-CSF), is commonly used to prevent febrile neutropenia (FN), a potentially life-threatening complication, following myelosuppressive chemotherapy. The FDA label for pegfilgrastim specifies that it should not be administered 14 days before or within 24 h of administration of myelosuppressive chemotherapy, precluding the use of pegfilgrastim in biweekly (Q2W) regimens. The National Comprehensive Cancer Network and the European Organisation for Research and Treatment of Cancer guidelines support the use of prophylactic pegfilgrastim in patients receiving Q2W regimens. The objective of this study was to systematically review evidence from randomized clinical trials (RCTs) and observational studies that describe the effectiveness and safety of prophylactic pegfilgrastim in preventing FN among patients receiving Q2W regimens.
METHODS
An Ovid MEDLINE, Embase, and Cochrane Library literature search was conducted to evaluate the evidence regarding efficacy, effectiveness, and safety of prophylactic pegfilgrastim versus no prophylactic pegfilgrastim or prophylaxis with other G-CSF in patients who were receiving Q2W chemotherapy regimens with high (> 20%) or intermediate (10-20%) risk of FN for a non-myeloid malignancy. Studies that addressed absolute or relative risk of FN, grade 1-4 neutropenia, all-cause or any hospitalization, dose delays or dose reductions, adverse events, or mortality were included. Studies where the comparator was a Q3W chemotherapy regimen with primary prophylactic pegfilgrastim were also included.
RESULTS
The initial literature search identified 2258 publications. Thirteen publications met the eligibility criteria, including eight retrospective, one prospective, one phase 1 dose escalation study, and three RCTs. In nine of the 13 studies reporting incidence of FN, and in seven of the nine studies reporting incidence of neutropenia, administration of prophylactic pegfilgrastim in patients receiving Q2W regimens resulted in decreased or comparable rates of FN or neutropenia compared with patients receiving filgrastim, no G-CSF, lipefilgrastim or pegfilgrastim in Q3W regimens. In six of the nine studies reporting safety data, lower or comparable safety profiles were observed between pegfilgrastim and comparators.
CONCLUSIONS
In a variety of non-myeloid malignancies, administration of prophylactic pegfilgrastim was efficacious in reducing the risk of FN in patients receiving high- or intermediate-risk Q2W regimens, with an acceptable safety profile.
TRIAL REGISTRATION
PROSPERO registration no: CRD42019155572 .
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy-Induced Febrile Neutropenia; Drug Administration Schedule; Filgrastim; Humans; Incidence; Polyethylene Glycols; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment
PubMed: 34044798
DOI: 10.1186/s12885-021-08258-w -
BMC Cancer Sep 2011Febrile neutropenia (FN) occurs following myelosuppressive chemotherapy and is associated with morbidity, mortality, costs, and chemotherapy reductions and delays.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Febrile neutropenia (FN) occurs following myelosuppressive chemotherapy and is associated with morbidity, mortality, costs, and chemotherapy reductions and delays. Granulocyte colony-stimulating factors (G-CSFs) stimulate neutrophil production and may reduce FN incidence when given prophylactically following chemotherapy.
METHODS
A systematic review and meta-analysis assessed the effectiveness of G-CSFs (pegfilgrastim, filgrastim or lenograstim) in reducing FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. G-CSFs were compared with no primary G-CSF prophylaxis and with one another. Nine databases were searched in December 2009. Meta-analysis used a random effects model due to heterogeneity.
RESULTS
Twenty studies compared primary G-CSF prophylaxis with no primary G-CSF prophylaxis: five studies of pegfilgrastim; ten of filgrastim; and five of lenograstim. All three G-CSFs significantly reduced FN incidence, with relative risks of 0.30 (95% CI: 0.14 to 0.65) for pegfilgrastim, 0.57 (95% CI: 0.48 to 0.69) for filgrastim, and 0.62 (95% CI: 0.44 to 0.88) for lenograstim. Overall, the relative risk of FN for any primary G-CSF prophylaxis versus no primary G-CSF prophylaxis was 0.51 (95% CI: 0.41 to 0.62). In terms of comparisons between different G-CSFs, five studies compared pegfilgrastim with filgrastim. FN incidence was significantly lower for pegfilgrastim than filgrastim, with a relative risk of 0.66 (95% CI: 0.44 to 0.98).
CONCLUSIONS
Primary prophylaxis with G-CSFs significantly reduces FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. Pegfilgrastim reduces FN incidence to a significantly greater extent than filgrastim.
Topics: Antineoplastic Combined Chemotherapy Protocols; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Neutropenia; Polyethylene Glycols; Recombinant Proteins; Treatment Outcome
PubMed: 21943360
DOI: 10.1186/1471-2407-11-404 -
Supportive Care in Cancer : Official... Nov 2015The study aims to assess the relative efficacy of granulocyte colony-stimulating factor (G-CSF) products administered as primary prophylaxis (PP) to patients with cancer... (Meta-Analysis)
Meta-Analysis Review
The impact of primary prophylaxis with granulocyte colony-stimulating factors on febrile neutropenia during chemotherapy: a systematic review and meta-analysis of randomized controlled trials.
PURPOSE
The study aims to assess the relative efficacy of granulocyte colony-stimulating factor (G-CSF) products administered as primary prophylaxis (PP) to patients with cancer receiving myelosuppressive chemotherapy.
METHODS
A systematic literature review identified publications (January 1990 to September 2013) of randomized controlled trials evaluating PP with filgrastim, pegfilgrastim, lenograstim, or lipegfilgrastim in adults receiving myelosuppressive chemotherapy for solid tumors or non-Hodgkin lymphoma. Direct, indirect, and mixed-treatment comparison (MTC) were used to estimate the odds ratio and 95 % credible interval of febrile neutropenia (FN) during cycle 1 and all cycles of chemotherapy combined without adjusting for differences in relative dose intensity (RDI) between study treatment arms.
RESULTS
Twenty-seven publications representing 30 randomized controlled trials were included. Using MTC over all chemotherapy cycles, PP with filgrastim, pegfilgrastim, lenograstim, and lipegfilgrastim versus no G-CSF PP or placebo were associated with statistically significantly reduced FN risk. FN risk was also significantly reduced with pegfilgrastim PP versus filgrastim PP. Over all chemotherapy cycles, there was a numerical but statistically nonsignificant increase in the FN risk for lipegfilgrastim PP versus pegfilgrastim PP. Using MTC in cycle 1, PP with filgrastim, pegfilgrastim, and lipegfilgrastim versus no G-CSF PP or placebo were associated with statistically significantly reduced FN risk.
CONCLUSIONS
In this meta-analysis, using MTC without adjustment for RDI, PP with all G-CSFs evaluated reduced the FN risk in patients receiving myelosuppressive chemotherapy. Future studies are needed to assess the influence of RDI on FN outcomes and to eliminate potential bias between G-CSF arms receiving more intensive chemotherapy than control arms.
Topics: Adult; Febrile Neutropenia; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Lenograstim; Lymphoma, Non-Hodgkin; Odds Ratio; Polyethylene Glycols; Primary Prevention; Randomized Controlled Trials as Topic; Recombinant Proteins
PubMed: 25821144
DOI: 10.1007/s00520-015-2686-9 -
Scientific Reports Oct 2019The optimum granulocyte colony-stimulating factor (G-CSF) treatment for cancer patients after being treated with cytotoxic chemotherapy remains unknown. Therefore, a... (Meta-Analysis)
Meta-Analysis
The optimum granulocyte colony-stimulating factor (G-CSF) treatment for cancer patients after being treated with cytotoxic chemotherapy remains unknown. Therefore, a systematic review and Bayesian network meta-analysis were performed to assess the efficacy and tolerability of 11 G-CSF drugs on patients after chemotherapy. A total of 73 randomized controlled trials (RCTs) containing 15,124 cancer patients were included for the final network meta-analysis. Compared with pegfilgrastim, there were a higher risk with filgrastim for incidence of febrile neutropenia (FN) (OR [95% CI]: 1.63 [1.07, 2.46]), and a higher risk with short-acting G-CSF (S-G-CSF) biosimilar and lenograstim for incidence of bone pain (BP) (OR [95% CI]: 6.45 [1.10, 65.73], 5.12 [1.14, 26.12], respectively). Mecapegfilgrastim, lipegfilgrastim and balugrastim were best G-CSF drugs in reducing FN (cumulative probabilities: 58%, 15%, 11%, respectively). S-G-CSF biosimilar, empegfilgrastim, and long-acting G-CSF (L-G-CSF) biosimilar were best G-CSF drugs in reducing severe neutropenia (SN) (cumulative probabilities: 21%, 20%, 15%, respectively). Mecapegfilgrastim, balugrastim, lipegfilgrastim and L-G-CSF biosimilar were best G-CSF drugs in reducing BP (cumulative probabilities: 20%, 14%, 8%, 8%, respectively). Mecapegfilgrastim, lipegfilgrastim and balugrastim might be the most appreciate G-CSF drugs with both good efficacy and tolerability when treating cancer patients after cytotoxic chemotherapy.
Topics: Bayes Theorem; Female; Granulocyte Colony-Stimulating Factor; Humans; Male; Neoplasms; Odds Ratio; Treatment Outcome
PubMed: 31653961
DOI: 10.1038/s41598-019-51982-4 -
Granulocyte-colony stimulating factor-associated aortitis in cancer: A systematic literature review.Cancer Treatment and Research... 2021Aortitis following granulocyte-colony stimulating factor (G-CSF) administration has been reported in 0.3-0.47% of cases. To evaluate the characteristics of...
BACKGROUND
Aortitis following granulocyte-colony stimulating factor (G-CSF) administration has been reported in 0.3-0.47% of cases. To evaluate the characteristics of G-CSF-associated aortitis, we systematically reviewed the literature.
METHODS
We searched PubMed and found 49 cases of G-CSF-associated aortitis and cancer comorbidities and analyzed their characteristics and treatments.
RESULTS
Since 2004, cases of G-CSF-associated aortitis have been increasing, particularly in Asia (75.5%). The mean age was 60.1 years; 79.6% of patients were 50 years and older; and most patients were females (91.8%). All patients underwent chemotherapy (taxane, 51.0%). The most frequent symptom was fever, which occurred within 10 days (61.2%) of G-CSF administration, similar to that in febrile neutropenia. The period to remission was within 14 days in 44.9% of cases. Steroids were administered to 59.2% of patients; however, treatment efficacy was not significant. No patients died.
CONCLUSIONS
High levels of inflammatory cytokines might induce aortitis; however, further studies are warranted.
Topics: Adult; Aged; Aortitis; Female; Granulocyte Colony-Stimulating Factor; Humans; Male; Middle Aged; Neoplasms
PubMed: 34530312
DOI: 10.1016/j.ctarc.2021.100454 -
BMC Health Services Research Dec 2022Febrile neutropenia (FN) is a prevalent and potentially life-threatening complication in patients with lymphoma receiving myelosuppressive chemotherapy. Pegfilgrastim is...
BACKGROUND
Febrile neutropenia (FN) is a prevalent and potentially life-threatening complication in patients with lymphoma receiving myelosuppressive chemotherapy. Pegfilgrastim is more effective than filgrastim as prophylaxis for FN. However, its usage has been limited because of its higher cost. Pegfilgrastim's value for money remains unclear.
OBJECTIVE
To systematically review the cost-effectiveness of pegfilgrastim compared to filgrastim as a primary or secondary prophylaxis for chemotherapy-induced FN among patients with lymphoma.
METHODS
A systematic literature search was conducted in PubMed, EMBASE, Cochrane Library databases, and Google Scholar. The most widely used economic evaluations (cost-effectiveness analysis, cost-utility analysis and cost-benefit analysis) were included in the review. Data extraction was guided by the Consolidated Health Economic Evaluation Reporting Standards checklist, and the quality of reviewed articles was assessed using the Joanna Briggs Institute (JBI) checklist. Cost-effectiveness data were rigorously summarized and synthesized narratively. Costs were adjusted to US$ 2020.
RESULTS
We identified eight economic evaluation studies (two cost-utility analyses, three cost-effectiveness analyses, and three studies reporting both cost-effectiveness and cost-utility analyses). Half of these studies were from Europe (n = 4), the other half were from Iran, USA, Canada, and Singapore. Six studies met > 80% of the JBI quality assessment criteria. Cost-effectiveness estimates in the majority (n = 6) of these studies were for Non-Hodgkin Lymphoma patients receiving myelosuppressive chemotherapy with high-risk of FN (> 20%). The studies considered a wide range of baseline FN risk (17-97.4%) and mortality rates (5.8-8.9%). Reported incremental cost-effectiveness ratios ranged from US$ 2199 to US$ 8,871,600 per quality-adjusted life-year (QALY) gained, dominant to US$ 44,358 per FN averted, and US$ 4261- US$ 7251 per life-years gained. The most influential parameters were medication and hospitalization costs, the relative risk of FN, and assumptions of mortality benefit.
CONCLUSIONS
Most studies showed that pegfilgrastim is cost-effective compared to filgrastim as primary and secondary prophylaxis for chemotherapy-induced FN among patients with lymphoma at a cost-effectiveness threshold of US$ 50,000 per QALY gained. The findings could assist clinicians and healthcare decision-makers to make informed decisions regarding resource allocation for the management of chemotherapy-induced FN in settings similar to those studied.
Topics: Humans; Filgrastim; Granulocyte Colony-Stimulating Factor; Cost-Benefit Analysis; Chemotherapy-Induced Febrile Neutropenia; Polyethylene Glycols; Antineoplastic Agents; Lymphoma; Recombinant Proteins; Febrile Neutropenia; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36585648
DOI: 10.1186/s12913-022-08933-z -
Journal of Global Oncology Sep 2018Despite widespread use of fluorouracil, epirubicin, cyclophosphamide, docetaxel (FEC-D) chemotherapy in breast cancer, the optimal strategy for primary febrile... (Meta-Analysis)
Meta-Analysis
PURPOSE
Despite widespread use of fluorouracil, epirubicin, cyclophosphamide, docetaxel (FEC-D) chemotherapy in breast cancer, the optimal strategy for primary febrile neutropenia (FN) prophylaxis remains unknown. A systematic review was therefore performed.
METHODS
Embase, Ovid MEDLINE, PubMed, Cochrane Database of Systematic Reviews, Cochrane Register of Controlled Trials, and conference proceedings were searched from 1946 to April 2016 for trials that reported the effectiveness of primary FN prophylaxis with FEC-D chemotherapy. Outcome measures were incidence of FN; treatment-related hospitalizations; chemotherapy dose delays, reductions, and discontinuations; and adverse events from prophylaxis.
RESULTS
Of 2,205 identified citations, eight studies (n = 1,250) met our eligibility criteria. Three additional studies (n = 293) were identified from a prior systematic review. Three randomized controlled trials (n = 576), one phase IV single-arm trial (n = 69), one prospective observational study (n = 37), and six retrospective studies (n = 861) were identified. Agents investigated were pegfilgrastim (n = 108), filgrastim (n = 1,119), and ciprofloxacin (n = 89). The heterogeneity of studies meant that a narrative synthesis of results was performed. Median FN rates for patients who received FEC-D with and without primary prophylaxis were 10.1% (interquartile range [IQR], 3.9% to 22.6%) and 23.9% (IQR, 9.2% to 27.3%), respectively. In the absence of primary prophylaxis, FN was more common during docetaxel than during FEC. Data from six studies showed a median rate of dose reductions and delays of 6.1% (IQR, 3.1% to 14.3%) and 19.3% (IQR, 10.5% to 32.8%), respectively, that occurred as a consequence of FN. Toxicity from prophylaxis itself was rarely reported.
CONCLUSION
Primary FN prophylaxis is effective in patients who receive FEC-D chemotherapy. The paucity of prospective data makes optimal recommendations about the choice and timing of prophylaxis challenging.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemoprevention; Cyclophosphamide; Docetaxel; Epirubicin; Febrile Neutropenia; Female; Fluorouracil; Humans; Risk Factors; Treatment Outcome
PubMed: 30241156
DOI: 10.1200/JGO.2016.008540 -
Value in Health : the Journal of the... Nov 2014
PubMed: 27202642
DOI: 10.1016/j.jval.2014.08.112