Impact of Primary Prophylaxis With Granulocyte Colony-Stimulating Factor on Febrile Neutropenia and Mortality in Adult Cancer Patients Receiving Chemotherapy: A Systematic Review

2007 ◽  
Vol 25 (21) ◽  
pp. 3158-3167 ◽  
Author(s):  
Nicole M. Kuderer ◽  
David C. Dale ◽  
Jeffrey Crawford ◽  
Gary H. Lyman
Keyword(s):  
Systematic Review ◽  
Febrile Neutropenia ◽  
Musculoskeletal Pain ◽  
Meta Analysis ◽  
Dose Intensity ◽  
Primary Prophylaxis ◽  
The Impact ◽  
Stimulating Factor ◽  
Disease Free ◽  
Related Mortality

Purpose Randomized controlled trials (RCTs) of prophylactic granulocyte colony-stimulating factors (G-CSF) have demonstrated a significant reduction in febrile neutropenia (FN) after systemic chemotherapy. Several RCTs have been published recently that investigate the impact of G-CSF on mortality and relative dose-intensity (RDI). Methods A comprehensive systematic review and meta-analysis of all reported RCTs comparing primary prophylactic G-CSF with placebo or untreated controls in adult solid tumor and malignant lymphoma patients was undertaken without language restrictions, using electronic databases, conference proceedings, and hand-searching techniques. Two reviewers extracted data independently. Summary estimates of relative risk (RR) with 95% CIs were estimated based on the method of Mantel-Haenszel and DerSimonian and Laird. Results Seventeen RCTs were identified including 3,493 patients. For infection-related mortality, RR reduction with G-CSF compared with controls was 45% (RR = 0.55; 95% CI, 0.33 to 0.90; P = .018); for early mortality (all-cause mortality during chemotherapy period), it was 40% (RR = 0.60; 95% CI, 0.43 to 0.83; P = .002); and for FN, it was 46% (RR = 0.54; 95% CI, 0.43 to 0.67; P < .001). Average RDI was significantly higher in patients who received G-CSF compared with control patients (P < .001). Bone or musculoskeletal pain was reported in 10.4% of controls and 19.6% of G-CSF patients (RR = 4.03; 95% CI, 2.15 to 7.52; P < .001). Significant reductions in FN with G-CSF were observed in studies allowing secondary G-CSF prophylaxis in controls and in the three trials with concurrent prophylactic antibiotics in both treatment arms. Conclusion Prophylactic G-CSF reduces the risk of FN and early deaths, including infection-related mortality, while increasing RDI and musculoskeletal pain. There are insufficient data to assess the impact of G-CSF on disease-free and overall survival.

Risk of hematological toxicities and febrile neutropenia in patients with hormone receptor-positive HER2-negative metastatic breast cancer treated with CDK 4/6 inhibitors: A systematic review and meta-analysis of randomized controlled trials.

2017 ◽  
Vol 35 (31_suppl) ◽  
pp. 207-207
Author(s):  
Myo Zaw ◽  
Kyaw Zin Thein ◽  
Aung Tun ◽  
Myat M. Han ◽  
Saba Radhi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Effects ◽  
Febrile Neutropenia ◽  
Randomized Controlled Trials ◽  
Financial Burden ◽  
Meta Analysis ◽  
Neutropenic Fever ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
The Impact

207 Background: Majority of breast cancers express the estrogen receptor or progesterone receptor. CDK4/6 signaling plays a role in endocrine therapy resistance and the benefit of inhibition of these pathways has been proven in studies. Yet the impact of these agents on hematological toxicities and febrile neutropenia is a considerable safety concern. Hence, we performed a systematic review and meta-analysis of randomized controlled trials (RCT). Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through June 2017 were queried. RCTs that mention anemia, thrombocytopenia, leukopenia, neutropenia and neutropenic fever as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% confidence interval (CI). Random effects model was applied. Results: Five RCTs (four phase 3 and one phase 2 studies) with a total of 2671 patients were eligible for analysis. The study arm used palbociclib-letrozole, palbociclib-fulvestrant, ribociclib-letrozole and abemaciclib-fulvestrant while the control arm utilized placebo in combination with letrozole or fulvestrant. The relative risks (RR) of all-grade side effects were as follows: anemia, 3.77 (95% CI: 2.47 – 5.75, p < 0.0001); thrombocytopenia, 9.69 (95% CI: 4.26 – 22.04, p < 0.0001); leukopenia, 11.68 (95% CI: 8.19–16.65; p < 0.0001); and neutropenia, 14.09 (95% CI: 10.73–18.49; p < 0.0001). The RR of high-grade adverse effects were as follows: anemia, 2.66 (95% CI: 1.29 – 5.45, p = 0.008); thrombocytopenia, 7.08 (95% CI: 1.95 – 25.74, p = 0.003); leukopenia, 33.58 (95% CI: 14.49–77.77; p < 0.0001); and neutropenia, 40.33 (95% CI: 19.34–84.10; p < 0.001). The pooled risk of neutropenic fever was statistically significant at 4.26 (95% CI: 1.11–16.26; p = 0.034). Conclusions: CDK 4/6 inhibitors based regimen significantly contributed to all hematological toxicities as well as febrile neutropenia. These toxicities affect patients’ quality of life, add financial burden and may lead to drug dosing inconsistencies.

scholarly journals Gender-Related Differences in Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis

Pulse ◽  
2021 ◽  
Vol 9 (1-2) ◽  
pp. 38-46
Author(s):  
Angkawipa Trongtorsak ◽  
Natchaya Polpichai ◽  
Sittinun Thangjui ◽  
Jakrin Kewcharoen ◽  
Ratdanai Yodsuwan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Hypertrophic Cardiomyopathy ◽  
Cohort Studies ◽  
Meta Analysis ◽  
Phenotypic Expression ◽  
Female Gender ◽  
Increased Risk ◽  
All Cause Mortality ◽  
The Impact ◽  
Related Mortality

<b><i>Background:</i></b> Gender-related differences in phenotypic expression and outcomes have been established in many cardiac conditions; however, the impact of gender in hypertrophic cardiomyopathy (HCM) remains unclear. We conducted a systematic review and meta-analysis to assess the differences in clinical outcomes between female and male HCM patients. <b><i>Methods:</i></b> We searched MEDLINE and EMBASE from inception to October 2020. Included were cohort studies that compared outcomes of interest including all-cause mortality, HCM-related mortality, and worsening heart failure (HF) or HF hospitalization between male and female. Data from each study were combined using the random effects model to calculate pooled odds ratio (OR) with 95% confidence interval (CI). <b><i>Results:</i></b> Eleven retrospective cohort studies with a total of 9,427 patients (3,719 females) were included. Female gender was significantly associated with an increased risk of all-cause mortality (pooled OR = 1.63, 95% CI: 1.26–2.10, <i>p</i> ≤ 0.001), HCM-related mortality (pooled OR = 1.47, 95% CI: 1.08–2.01, <i>p</i> = 0.015), and worsening HF or HF hospitalization (pooled OR = 2.05, 95% CI: 1.76–2.39, <i>p</i> ≤ 0.001). <b><i>Conclusions:</i></b> Female gender was associated with a worse prognosis in HCM. These findings suggest the need for improved care in women including early identification of disease and more possible aggressive management. Moreover, gender-based strategy may benefit in HCM patients.

Impact of Febrile Neutropenia and Colony Stimulating Factor Use on Chemotherapy Delivery in Patients with Lymphoma: Results from the INC-EU Prospective Observational European Neutropenia Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2444-2444
Author(s):  
Ruth Pettengell ◽  
Andre Bosly ◽  
Thomas D. Szucs ◽  
Christian Jackisch ◽  
Robert Leonard ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Hodgkin Lymphoma ◽  
Performance Status ◽  
Dose Intensity ◽  
Primary Prophylaxis ◽  
Routine Practice ◽  
Colony Stimulating Factor ◽  
Ecog Performance Status ◽  
New Guidelines ◽  
Stimulating Factor

Abstract New guidelines from 3 professional organisations (EORTC, ASCO and NCCN) highlight the importance of identifying patients at risk of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) and providing preventative therapy to avert infection-related consequences and impaired treatment delivery. This prospective observational study was conducted to assess the incidence and predictors of CIN, FN and reduced chemotherapy administration in routine practice in Western Europe. Lymphoma patients starting new chemotherapy regimens were enrolled from 34 centres in Belgium, France, Germany, Spain and the UK. Treatment was as per usual clinical practice, except for one additional blood count at cycle 1 neutrophil nadir. Of the total 305 patients, 65 (21%) had Hodgkin lymphoma (HL) and 240 (79%) had non-Hodgkin lymphoma (NHL). Mean age at diagnosis ± SD was 39 ± 17 years for HL and 63 ± 13 years for NHL. Ann Arbour stages were distributed, I 9%; II 52%; III 19%; IV 20% in the HL group. In the NHL group, stages were distributed I 18%; II 26%; III 16%; IV 40%. Chemotherapy regimens for HL patients were mainly ABVD-like (72%), BEACOPP-like (12%) and Stanford V (8%); regimens for NHL patients were 3-weekly CHOP-like (74%), followed by 2-weekly CHOP-like (17%), ACVBP-like (4%) and NHL other (5%). Primary colony stimulating factor (CSF) prophylaxis was used in 18% of HL and 28% of NHL patients; whereas 37% of HL and 29% of NHL patients received secondary CSF prophylaxis. Primary CSF use by regimen type was: ABVD-like 9%; BEACOPP-like 63%; Stanford V 20%; 3-weekly CHOP-like 12%; 2-weekly CHOP-like 76%; ACVBP-like 56%; and NHL other 67%. FN occurred in 15% (95% CI 8–27%) of HL and 22% (CI 17–28%) of NHL patients. FN occurrence was ≥ 20% for BEACOPP-like; Stanford V; 3-weekly CHOP-like; ACVBP-like; and NHL other regimens. Grade 4 CIN was observed in 40% (CI 28–53%) of HL and 54% (CI 47–60%) of NHL patients. Neutropenia-related hospitalisations were reported for 14% of HL and 18% of NHL patients. Mean relative chemotherapy dose intensity (RDI) ± SD compared to plan, taking into account non-administered cycles, was 88 ± 13% for HL and 86 ± 21% for NHL. Low RDI (≤ 85%) was observed in 31% and 32% of HL and NHL patients, respectively. Multivariate logistic regression confirmed first cycle FN and fewer cycles with CSF use as predictors of low RDI (table). In line with new guidelines for CSF support during myelosuppressive chemotherapy, routine European practice should be revised to include primary prophylaxis with CSF for regimens where an FN incidence of ≥ 20% was seen (e.g. 3-weekly CHOP), and where less than optimal RDI was attained. This study was supported by Amgen (Europe) GmbH. Predictors of RDI ≤ 85% Odds ratio (95% CI) † 3-weekly CHOP-like, reference category, p = 0.018 for this set of covariates. Age (per additional 10 years of age) 1.38 (1.13–1.70) ECOG performance status ≥ 2 2.39 (1.12–5.11) Type of chemotherapy regimen †: 2-weekly CHOP-like 2.04 (0.90–4.65) ACVBP-like 9.48 (2.12–42.40) NHL other 1.98 (0.56–6.91) ABVD-like 2.71 (1.09–6.76) HL other 3.19 (0.96–10.65) Cycles with CSF administration (per additional cycle with CSF) 0.85 (0.76–0.96) Cycle 1 FN occurrence 2.82 (1.16–6.86)

Prophylactic Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor Decrease Febrile Neutropenia After Chemotherapy in Children With Cancer: A Meta-Analysis of Randomized Controlled Trials

2004 ◽  
Vol 22 (16) ◽  
pp. 3350-3356 ◽  
Author(s):  
Lillian Sung ◽  
Paul C. Nathan ◽  
Beverly Lange ◽  
Joseph Beyene ◽  
George R. Buchanan
Keyword(s):  
Febrile Neutropenia ◽  
Amphotericin B ◽  
Rate Ratio ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Colony Stimulating Factor ◽  
Weighted Mean ◽  
Parenteral Antibiotic ◽  
Stimulating Factor ◽  
Related Mortality

Purpose To determine whether prophylactic hematopoietic colony-stimulating factors (CSFs) used in children with cancer reduce the rate of febrile neutropenia, hospitalization duration, documented infection rate, parenteral antibiotic duration, amphotericin B use, or infection-related mortality. Methods We included studies in this meta-analysis if their populations consisted of children, if there was randomization between CSFs and placebo or no therapy, if CSFs were administered prophylactically (before neutropenia or febrile neutropenia), and if chemotherapy treatments preceding CSFs and placebo or no therapy were identical. From 971 reviewed study articles, 16 were included. Results The mean rate of febrile neutropenia in the control arms was 57% (range, 39% to 100%). Using a random effects model, CSFs were associated with a reduction in febrile neutropenia, with a rate ratio of 0.80 (95% CI, 0.67 to 0.95; P = .01), and a decrease in hospitalization length, with a weighted mean difference of −1.9 days (95% CI, −2.7 to −1.1 days; P < .00001). CSF use was also associated with reduction in documented infections (rate ratio, 0.78; 95% CI, 0.62 to 0.97; P = .02) and reduction in amphotericin B use (rate ratio, 0.50; 95% CI, 0.28 to 0.87; P = .02). There was no difference in duration of parenteral antibiotic therapy (weighted mean difference, −4.3; 95% CI, −10.6 to 2.0 days; P = .2) or infection-related mortality (rate ratio, 1.02; 95% CI, 0.34 to 3.06; P = .97). Conclusion CSFs were associated with a 20% reduction in febrile neutropenia and shorter duration of hospitalization; however, CSFs did not reduce infection-related mortality.

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

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4850-4850
Author(s):  
Li Wang ◽  
Onur Baser ◽  
Lucie Kutikova ◽  
John H Page ◽  
Richard L Barron
Keyword(s):  
Systematic Review ◽  
Febrile Neutropenia ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Primary Prophylaxis ◽  
Controlled Trials ◽  
Employment Equity ◽  
Myelosuppressive Chemotherapy ◽  
Randomized Controlled ◽  
Equity Ownership

Abstract Introduction Febrile neutropenia (FN) is a dose-limiting toxicity of myelosuppressive chemotherapy that has been associated with decreased chemotherapy relative dose intensity (RDI) and increased morbidity and mortality. In clinical trials, primary prophylaxis (PP) with recombinant human granulocyte colony-stimulating factors (G-CSFs) has been shown to reduce the risk of FN, chemotherapy dose delays/reductions, decreased RDI, antibiotic use, and FN-related hospitalization. This systematic review and meta-analysis assessed the relative efficacy of PP with different G-CSFs to reduce the incidence of FN in cancer patients who received myelosuppressive chemotherapy in randomized controlled trials (RCTs). Methods A systematic literature review identified publications (January 1990 to September 2013) of RCTs assessing PP with filgrastim, pegfilgrastim, lenograstim, or lipegfilgrastim versus placebo, no G-CSF PP, or a different G-CSF in adults who received myelosuppressive chemotherapy for solid tumors or non-Hodgkin's lymphoma. Terms for G-CSFs were searched for in PubMed, Embase, Science Citation Index, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database, and the National Health Service Economic Evaluation Database; original publications were searched manually. Eligible studies enrolled patients who initiated G-CSF PP 1–3 days after completing chemotherapy in each cycle; control patients were eligible for secondary prophylaxis with the same G-CSF after the first cycle. Study exclusion criteria included granulocyte-macrophage colony-stimulating factor use, leukemia or multiple myeloma, bone marrow or peripheral blood stem cell transplantation, G-CSF for established FN, different doses of the same G-CSF in each treatment arm, and investigational or unapproved drugs. Economic analyses and studies published in languages other than English were excluded. A meta-analysis using mixed-treatment comparison (MTC) was used to calculate the odds ratio (OR) and 95% credible interval of FN in all chemotherapy cycles and in cycle 1 without adjustment for differences in RDI between study treatment arms. No adjustment for differences in RDI between arms was made because RDI was not consistently reported between studies. Results Of the 4790 publications initially screened, 27 publications representing 30 studies were included in the meta-analysis (Figure). Over all chemotherapy cycles, there was a statistically significant reduction in the FN risk for PP with filgrastim, pegfilgrastim, lenograstim, and lipegfilgrastim versus no G-CSF PP or placebo, as well as with pegfilgrastim PP versus filgrastim PP (Table). Over all chemotherapy cycles, there was a statistically nonsignificant increase in the FN risk for lipegfilgrastim PP versus pegfilgrastim PP; a statistically significant difference was not expected because of the small sample size (n=306) for lipegfilgrastim (2 studies). During chemotherapy cycle 1, there was a statistically significant reduction in the FN risk for filgrastim PP versus no G-CSF PP or placebo, pegfilgrastim PP versus no G-CSF PP or placebo, and lipegfilgrastim PP versus no G-CSF or placebo (data not shown). Conclusions Using MTC without adjustment for RDI, PP with short-acting and long-acting G-CSFs was associated with a reduced FN risk in patients receiving myelosuppressive chemotherapy for solid tumors or non-Hodgkin's lymphoma. In future studies, consistent reporting of RDI between study arms is needed to adequately assess the influence of RDI on FN outcomes and to eliminate the potential bias in comparisons between G-CSF arms receiving more intensive chemotherapy than control arms. Figure 1 Figure 1. Table Primary prophylaxis comparisons across all cycles Median OR (95% CrI) Filgrastim vs no G-CSF or placebo (11 studies; n=2181) 0.42 (0.30–0.57) Pegfilgrastim vs no G-CSF or placebo (5 studies; n=2060) 0.25 (0.17–0.40) Lenograstim vs no G-CSF or placebo (5 studies; n=467) 0.34 (0.19–0.60) Lipegfilgrastim vs no G-CSF or placebo (1 study; n=375) 0.35 (0.14–0.88) Pegfilgrastim vs filgrastim (6 studies; n=647) 0.61 (0.40–0.98) Lipegfilgrastim vs pegfilgrastim (2 studies; n=306) 1.39 (0.54–3.50) Heterogeneity, between-trial SD logOR, mean (95% CI) 0.41 (0.17–0.69) Mean residual difference 60.01 Disclosures Wang: Amgen Inc.: Consultancy. Baser:Amgen Inc.: Consultancy. Kutikova:Amgen Inc.: Employment, Equity Ownership. Page:Amgen Inc.: Employment, Equity Ownership. Barron:Amgen Inc.: Employment, Equity Ownership.

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