Chemotherapy-induced Febrile Neutropenia Research Articles

Chemotherapy-induced febrile neutropenia (FN): healthcare resource utilization (HCRU) and costs in commercially insured patients in the US

PurposeFebrile neutropenia (FN) is a known side effect of chemotherapy, often requiring hospitalization. Economic burden increases with an FN episode and estimates of cost per episode should be updated from real-world data.MethodsA retrospective claims analysis of FN episodes in patients with non-myeloid malignancies from 2014 to 2021 was performed in IQVIA PharMetrics® Plus database. FN episodes were defined as having same-day claims for neutropenia and fever or infection, plus antibiotic in outpatient settings, following a claim for chemotherapy; index date was defined as the first claim for neutropenia/fever/infection. Patients receiving bone marrow/stem cell transplant and CAR-T therapy were excluded, as were select hematologic malignancies or COVID-19. Healthcare utilization and costs were evaluated and described overall, by episode type (w/wo hospitalization), index year, malignancy type, NCI comorbidity score, and age group.Results7,033 FN episodes were identified from 6,825 patients. Most episodes had a hospitalization (91.2%) and 86% of patients had ≥1 risk factor for FN. Overall, FN episodes had a mean (SD) FN-related cost of $25,176 ($39,943). Episodes with hospitalization had higher average FN-related costs versus those without hospitalization ($26,868 vs $7,738), and costs increased with comorbidity score (NCI=0: $23,095; NCI >0-2: $26,084; NCI ≥2: $26,851).ConclusionsFN continues to be associated with significant economic burden, and varied by cancer type, comorbidity burden, and age. In this analysis, most FN episodes were not preceded by GCSF prophylaxis. The results of this study highlight the opportunity to utilize GCSF in appropriate oncology scenarios.

Therapeutic use of granulocyte colony-stimulating factor (G-CSF) in patients with febrile neutropenia: a comprehensive systematic review for clinical practice guidelines for the use of G-CSF 2022 from the Japan Society of Clinical Oncology.

Febrile neutropenia represents a critical oncologic emergency, and its management is pivotal in cancer therapy. In several guidelines, the use of granulocyte colony-stimulating factor (G-CSF) in patients with chemotherapy-induced febrile neutropenia is not routinely recommended except in high-risk cases. The Japan Society of Clinical Oncology has updated its clinical practice guidelines for the use of G-CSF, incorporating a systematic review to address this clinical question. The systematic review was conducted by performing a comprehensive literature search across PubMed, the Cochrane Library, and Ichushi-Web, focusing on publications from January 1990 to December 2019. Selected studies included randomized controlled trials (RCTs), non-RCTs, and cohort and case-control studies. Evaluated outcomes included overall survival, infection-related mortality, hospitalization duration, quality of life, and pain. The initial search yielded 332 records. Following two rounds of screening, two records were selected for both qualitative and quantitative synthesis including meta-analysis. Regarding infection-related mortality, the event to case ratio was 5:134 (3.73%) in the G-CSF group versus 6:129 (4.65%) in the non-G-CSF group, resulting in a relative risk of 0.83 (95% confidence interval, 0.27-2.58; p = 0.54), which was not statistically significant. Only median values for hospitalization duration were available from the two RCTs, precluding a meta-analysis. For overall survival, quality of life, and pain, no suitable studies were found for analysis, rendering their assessment unfeasible. A weak recommendation is made that G-CSF treatment not be administered to patients with febrile neutropenia during cancer chemotherapy. G-CSF treatment can be considered for patients at high risk.

HSR24-146: Chemotherapy-Induced Febrile Neutropenia (FN) in the US: Healthcare Resource Utilization (HCRU) and Costs.

HSR24-146: Chemotherapy-Induced Febrile Neutropenia (FN) in the US: Healthcare Resource Utilization (HCRU) and Costs.

Effectiveness of G-CSF in chemotherapy for digestive system tumors: a systematic review of the Clinical Practice Guidelines for the Use of G-CSF 2022 delineated by the Japan Society of Clinical Oncology.

Granulocyte colony-stimulating factor (G-CSF) reportedly reduces the risk of neutropenia and subsequent infections caused by cancer chemotherapy. Although several guidelines recommend using G-CSF in primary prophylaxis according to the incidence rate of chemotherapy-induced febrile neutropenia (FN), the effectiveness of G-CSF in digestive system tumor chemotherapy remains unclear. To address these clinical questions, we conducted a systematic review as part of revising the Clinical Practice Guidelines for the Use of G-CSF 2022 published by the Japan Society of Clinical Oncology. This systematic review addressed two main clinical questions (CQ): CQ1: "Is primary prophylaxis with G-CSF effective in chemotherapy?", and CQ2: "Is increasing the intensity of chemotherapy with G-CSF effective?" We reviewed different types of digestive system tumors, including esophageal, gastric, pancreatic, biliary tract, colorectal, and neuroendocrine carcinomas. PubMed, Cochrane Library, and Ichushi-Web databases were searched for information sources. Independent systematic reviewers conducted two rounds of screening and selected relevant records for each CQ. Finally, the working group members synthesized the strength of evidence and recommendations. After two rounds of screening, 5/0/3/0/2/0 records were extracted for CQ1 of esophageal/gastric/pancreatic/biliary tract/colorectal/ and neuroendocrine carcinoma, respectively. Additionally, a total of 2/6/1 records were extracted for CQ2 of esophageal/pancreatic/colorectal cancer, respectively. The strength of evidence and recommendations were evaluated for CQ1 of colorectal cancer; however, we could not synthesize recommendations for other CQs owing to the lack of records. The use of G-CSF for primary prophylaxis in chemotherapy for colorectal cancer is inappropriate.

Pattern of Bacterial Infections in Paediatric Patients with Chemotherapy-Induced Neutropenia

Objectives: To determine the frequency of bacterial infections and their sensitivity to various antibiotics in paediatric cancer patients having chemotherapy-induced neutropenia. Study Design: Cross-sectional study Place and Duration of Study: Paediatric Oncology ward, Combined Military Hospital, Rawalpindi Pakistan, from Jul 2018 to Jan 2019. Methodology: A total of 205 children aged one year to 12 years undergoing chemotherapy and having neutropenic fever were included. Complete history, full physical examination and related blood, microbiological and radiological investigations were undertaken. Antibiotics were given as per protocol. Results: In our study, the bacterial infections in paediatric cancer patients with chemotherapy-induced neutropenia was found in 45(21.95%) patients. Of these, gram-positive organisms were found in 25(55.5%) patients and gram-negative in 20(44.4%). Conclusion: The frequency of bacterial infections in paediatric patients with chemotherapy-induced febrile neutropenia is quite high, with a high percentage of gram-positive bacteria.

ASSOCIATION OF FEBRILE NEUTROPENIA WITH CHEMOTHERAPEUTIC AGENTS IN MALIGNANCIES

Introduction: Chemotherapy-induced febrile neutropenia (FN) is associated with substantial morbidity, mortality, and healthcare costs. The aim of this study was to evaluate episodes of FN in patients with malignancies, to find out the association of FN with various chemotherapeutic regimens, and to identify the microorganisms and the factors affecting the outcome. Methods: All patients with FN were admitted and detailed history was taken with thorough clinical evaluation. Blood, urine, and throat swab cultures and cultures from any other clinically evident site of infection were sent to all the patients. Results: Most common diagnosis was Ca breast and non-Hodgkin’s lymphoma in 13 patients. The ECOG performance status of 2 was seen in 61% of patients. The FN episodes (11%) were associated with carboplatin plus paclitaxel, and in patients with Ca cervix, Ca esophagus, and Ca ovary. The chest was involved in 16% of patients followed by the GI tract in 10%. Pseudomonas aeruginosa organism growth was seen in a 50% sample of throat swabs. The mean number of days of chemotherapy, after which patients reported to have FN, was 3.6, and median (interquartile range [IQR]) days was 2. Granulocyte colony-stimulating factor was administered in all patients in this study. The mean number of days of recovery of the patients was 4.9 and median (IQR) days was 4. Conclusion: The episodes of FN occurred mostly in patients with Ca breast, followed by non-Hodgkin’s lymphoma. FN was more commonly seen with taxanes.

How Asian Breast Cancer Patients Experience Unequal Incidence of Chemotherapy Side Effects: A Look at Ethnic Disparities in Febrile Neutropenia Rates.

The majority of published findings on chemotherapy-induced febrile neutropenia (FN) are restricted to three ethnic groups: Asians, Caucasians, and African Americans. In this two-part study, we examined FN incidence and risk factors in Chinese, Malay, and Indian chemotherapy-treated breast cancer (BC) patients. Hospital records or ICD codes were used to identify patients with FN. In both the Singapore Breast Cancer Cohort (SGBCC) and the Joint Breast Cancer Registry (JBCR), the time of the first FN from the start of chemotherapy was estimated using Cox regression. Multinomial regression was used to evaluate differences in various characteristics across ethnicities. FN was observed in 170 of 1014 patients in SGBCC. The Cox model showed that non-Chinese were at higher risk of developing FN (HRMalay [95% CI]:2.04 [1.44-2.88], p < 0.001; HRIndian:1.88 [1.11-3.18], p = 0.018). In JBCR, FN was observed in 965 of 7449 patients. Univariable Cox models identified ethnicity, a lower baseline absolute neutrophil count, non-luminal A proxy subtypes, and anthracycline-containing regimens as risk factors. Disparities across ethnicities' risk (HRMalay:1.29 [1.07-1.54], p = 0.006; HRIndian:1.50 [1.19-1.88], p < 0.001) remained significant even after further adjustments. Finally, an age-adjusted multinomial model showed that Malays (p = 0.006) and Indians (p = 0.009) were significantly more likely to develop multiple episodes of FN during treatment. Ethnic differences in chemotherapy-induced FN among BC patients exist. Further studies can focus on investigating pharmacogenetic differences across ethnicities.

Eflapegrastim (Rolvedon) for prevention of chemotherapy-induced febrile neutropenia.

Eflapegrastim-xnst (Rolvedon [Spectrum]; previously called Rolontis), a granulocyte colony-stimulating factor (G-CSF) conjugated to an Fc fragment of human IgG4, has been approved by the FDA to decrease the incidence of infection, as manifested by febrile neutropenia, in adults with nonmyeloid malignancies receiving myelosuppressive chemotherapy that can cause clinically significant febrile neutropenia.

The Role of Granulocyte-Colony Stimulating Factor Biosimilars for Supportive Cancer Care: A Year in Review

This year-in-review article provides insights into clinical updates relating to granulocyte-colony stimulating factor (G-CSF) biosimilars research presented at five key congresses in 2022. These include the American Society of Clinical Oncology (ASCO) 55th Annual Meeting (3rd–7th June 2022, Chicago, Illinois, USA), European Society for Medical Oncology (ESMO) Congress (9th–13th September 2022, Paris, France), ESMO Asia Congress (2nd–4th December 2022, Singapore), San Antonio Breast Cancer Symposium (SABCS; 6th–10th December 2022, Texas, USA), and American Society of Hematology (ASH) 64th Annual Meeting and Exposition (10th–13th December 2022, New Orleans, Louisiana, USA). Alongside reviewing the current research presented at these key congresses, with a focus on the use of G-CSF agents and biosimilars in patients undergoing treatment for breast, colorectal, and gynaecological cancers, this article provides an overview of current guidelines on the use of G-CSF in supportive cancer care to manage chemotherapy-induced febrile neutropenia and explores trends in G-CSF biosimilars research.

Risk factors and predictors of adverse outcomes of in paediatric febrile neutropenia

Background: Febrile neutropenia (FN) is the commonest acute complication of cancer treatment in children. The identification of patients at risk for FN as well as adverse outcomes has been described.Aim: To evaluate the prevalence and potential risk factors for FN and describe adverse outcomes in a cohort of children treated for cancer.Setting: The study was carried out in a paediatric oncology unit in a children’s hospital, Cape Town, South Africa.Methods: A retrospective study from 01 January 2017 to 31 December 2019 on children with cancer at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa.Results: Two hundred and sixty-seven episodes of FN occurred in 179 patients. Independent predictors of FN were acute myeloid leukaemia (AML) (p = 0.039), acute lymphocytic leukaemia (ALL) (p = 0.020) and intensive chemotherapy (p ≤ 0.001). Mucositis (p = 0.001), central venous access device (CVAD) placement (p = 0.004), haematologic malignancies (p = 0.040), blood transfusion during FN episode (p 0.001) and severe neutropenia (white cell counts 0.3 × 109 cells/L) (p ≤ 0.001) were risk factors for adverse outcomes. The mortality rate from FN was 3.57%. Independent predictors of adverse outcomes in those with FN were AML (p = 0.001), CVAD placement (p = 0.019) and severe neutropenia (p = 0.005).Conclusion: Treatment related adverse outcomes following chemotherapy-induced FN are likely in children with AML, severe neutropenia and with CVAD placement.Contribution: Adverse outcomes from paediatric febrile neutropenia is high. There is need for clinical decision making aimed at prevention and early identification of individuals at risk.

Clinical factors predicting return emergency department visits in chemotherapy-induced febrile neutropenia patients

BackgroundAlthough chemotherapy-induced febrile neutropenia (FN) is the most common and life-threatening oncologic emergency, the characteristics and outcomes associated with return visits to the emergency department (ED) in these patients are uncertain. Hence, we aimed to investigate the predictive factors and clinical outcomes of chemotherapy-induced FN patients returning to the ED. MethodThis single-center, retrospective observational study spanning 14 years included chemotherapy-induced FN patients who visited the ED and were discharged. The primary outcome was a return visit to the ED within five days. We conducted logistic regression analyses to evaluate the factors influencing ED return visit. ResultsThis study included 1318 FN patients, 154 (12.1%) of whom revisited the ED within five days. Patients (53.3%) revisited the ED owing to persistent fever (56.5%), with no intensive care unit admission and only one mortality case who was discharged hopelessly. Multivariable analysis revealed that shock index >0.9 (odds ratio [OR]: 1.45, 95% confidence interval [CI], 1.01–2.10), thrombocytopenia (<100 × 103/uL) (OR: 1.64, 95% CI, 1.11–2.42), and lactic acid level > 2 mmol/L (OR: 1.51, 95% CI, 0.99–2.25) were associated with an increased risk of a return visit to the ED, whereas being transferred into the ED from other hospitals (OR: 0.08; 95% CI, 0.005–0.38) was associated with a decreased risk of a return visit to the ED. ConclusionHigh shock index, lactic acid, thrombocytopenia, and ED arrival type can predict return visits to the ED in chemotherapy-induced FN patients.

Risk of chemotherapy-induced febrile neutropenia in intermediate-risk regimens: Clinical and economic outcomes of granulocyte colony-stimulating factor prophylaxis.

BACKGROUND: Chemotherapy-induced neutropenia increases the risk of febrile neutropenia (FN) and infection with resultant hospitalizations, with substantial health care resource utilization (HCRU) and costs. Granulocyte-colony stimulating factor (GCSF) is recommended as primary prophylaxis for chemotherapy regimens having more than a 20% risk of FN. Yet, for intermediate-risk (10%-20%) regimens, it should be considered only for patients with 1 or more clinical risk factors (RFs) for FN. It is unclear whether FN prophylaxis for intermediate-risk patients is being optimally implemented. OBJECTIVE: To examine RFs, prophylaxis use, HCRU, and costs associated with incident FN during chemotherapy. METHODS: This retrospective study used administrative claims data for commercial and Medicare Advantage enrollees with nonmyeloid cancer treated with intermediate-risk chemotherapy regimens during January 1, 2009, to March 31, 2020. Clinical RFs, GCSF prophylaxis, incident FN, HCRU, and costs were analyzed descriptively by receipt of primary GCSF, secondary GCSF, or no GCSF prophylaxis. Multivariable Cox regression analysis was used to examine the association between number of RFs and cumulative FN risk. RESULTS: The sample comprised 13,937 patients (mean age 67 years, 55% female). Patients had a mean of 2.3 RFs, the most common being recent surgery, were aged 65 years or greater, and had baseline liver or renal dysfunction; 98% had 1 or more RFs. However, only 35% of patients received primary prophylaxis; 12% received secondary prophylaxis. The hazard ratio of incident FN was higher with increasing number of RFs during the first line of therapy, yet more than 54% of patients received no prophylaxis, regardless of RFs. Use of GCSF prophylaxis varied more by chemotherapeutic regimen than by number of RFs. Among patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine, and prednisone, 76% received primary prophylaxis, whereas only 22% of patients treated with carboplatin/paclitaxel received primary prophylaxis. Among patients with a first line of therapy FN event, 78% had an inpatient stay and 42% had an emergency visit. During cycle 1, mean FN-related coordination of benefits-adjusted medical costs per patient per month ($13,886 for patients with primary prophylaxis and $18,233 for those with none) were driven by inpatient hospitalizations, at 91% and 97%, respectively. CONCLUSIONS: Incident FN occurred more often with increasing numbers of RFs, but GCSF prophylaxis use did not rise correspondingly. Variation in prophylaxis use was greater based on regimen than RF number. Lower health care costs were observed among patients with primary prophylaxis use. Improved individual risk identification for intermediate-risk regimens and appropriate prophylaxis may decrease FN events toward the goal of better clinical and health care cost outcomes. DISCLOSURES: This work was funded by Sandoz Inc., which participated in the design of the study, interpretation of the data, writing and revision of the manuscript, and the decision to submit the manuscript for publication. The study was performed by Optum under contract with Sandoz Inc. The author(s) meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. The authors received no direct compensation related to the development of the manuscript. Dr Li is an employee of Sandoz Inc. Drs Bell and Lal and Mr Peterson-Brandt were employees of Optum at the time of the study. Ms Anderson and Dr Aslam are employees of Optum. Dr Lyman has been primary investigator on a research grant from Amgen to their institution and has consulted for Sandoz, G1 Therapeutics, Partners Healthcare, BeyondSpring, ER Squibb, Merck, Jazz Pharm, Kallyope, Teva; Fresenius Kabi, Seattle Genetics, and Samsung.

Cost-effectiveness of pegfilgrastim versus filgrastim for prevention of chemotherapy-induced febrile neutropenia in patients with lymphoma: a systematic review

BackgroundFebrile 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.ObjectiveTo systematically review the cost-effectiveness of pegfilgrastim compared to filgrastim as a primary or secondary prophylaxis for chemotherapy-induced FN among patients with lymphoma.MethodsA 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.ResultsWe 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.ConclusionsMost 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.

Efficacy of same-day versus next-day administration of pegfilgrastim for the prevention of chemotherapy-induced febrile neutropenia in breast cancer patients receiving dose-dense doxorubicin and cyclophosphamide: A retrospective multi-site analysis.

Administering pegfilgrastim on the same day as chemotherapy can improve patient satisfaction through convenience and may increase the utilization of cost-effective biosimilars compared to next-day administration, but the effect on clinical outcomes with commonly used breast cancer regimens is unclear. This multi-site, retrospective cohort study included breast cancer patients age 18 years or older who received dose-dense doxorubicin and cyclophosphamide (ddAC) and pegfilgrastim between 1 June 2016 and 31 May 2020. Pegfilgrastim was given on the same day as chemotherapy at one site and the day after chemotherapy at the other two sites. The primary endpoint compared the incidence of febrile neutropenia associated with pegfilgrastim administration timing. A total of 360 patients were reviewed (146 same-day administration and 214 next-day administration). In the same-day group 36 patients (24.6%) developed FN compared to 25 patients (11.7%) in the next-day group (p = 0.002). Same-day administration also significantly increased the incidences of additional acute care visits (11.6% vs 2.8%, p = 0.0016), grade ≥ 3 neutropenia (38.4% vs 13.6%, p < 0.0001), chemotherapy dose reductions (21.2% vs 6.1%, p < 0.0001), and antibiotic use (26.7% vs 12.6%, p = 0.001). Same-day administration did not significantly increase the rate of hospitalization (15% vs 11.2%, p = 0.36) and delay of next chemotherapy cycle by ≥1 day (8.2% vs 6.1%, p = 0.57) due to neutropenic complications. Administering pegfilgrastim on the same day as ddAC led to a significant increase in neutropenic complications. This study confirms the need to administer pegfilgrastim the day after chemotherapy in breast cancer patients receiving ddAC.

EPH129 Hospitalizations for Chemotherapy-Induced Febrile Neutropenia in Patients With Lung Cancer in France From 2017 to 2020

EPH129 Hospitalizations for Chemotherapy-Induced Febrile Neutropenia in Patients With Lung Cancer in France From 2017 to 2020

Predictive Factors of Febrile Neutropenia After Primary Prophylactic Pegfilgrastim With DCF Chemotherapy for Esophageal Cancer.

We investigated the predictive factors of febrile neutropenia (FN) after the administration of pegfilgrastim as primary prophylaxis in patients with esophageal cancer who received neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF) to support the appropriate management of FN. We evaluated changes in neutrophil counts and relative dose intensity (RDI) after the incidence of FN. This retrospective study involved 122 patients with esophageal cancer who were treated with DCF and pegfilgrastim at Showa University Hospital, Japan, between April 2016 and August 2021. The primary outcome was FN incidence after cycle 1 of DCF chemotherapy. The significant independent factors associated with FN incidence were selected using the multivariate analysis. Changes in neutrophil counts and RDI were compared between the FN and non-FN groups. One-hundred patients were included in the analysis. The incidence of FN in cycle 1 was 21%. In the multivariate analysis, geriatric nutritional risk index (GNRI) <92 [odds ratio (OR)=13.162, p<0.001] and combination of platelet and neutrophil-to-lymphocyte ratio (COP-NLR) score of 0 (OR=4.619, p=0.012) were independent predictors of FN. The neutrophil count on day 7-10 and RDI in the FN group were lower than those in the non-FN group (all p<0.05). GNRI <92 and COP-NLR score of 0 are important indicators to predict patients at high risk of DCF chemotherapy-induced FN. Furthermore, FN incidence after pegfilgrastim administration had a strong effect on delayed neutrophil recovery and reduced RDI.

COVID-19 Prevention Guidance and the Incidence of Febrile Neutropenia in Patients with Breast Cancer Receiving TAC Chemotherapy with Prophylactic Pegfilgrastim

Chemotherapy-induced febrile neutropenia (FN) is a medical emergency that causes severe adverse effects and death. Respiratory infections are one of the main causes of fever in patients with FN. We studied whether infection prevention and control (IPC) guidance for coronavirus 2019 disease reduced the incidence of FN. We reviewed female patients with breast cancer treated with adjuvant docetaxel, doxorubicin, and cyclophosphamide with prophylactic pegfilgrastim between 2019 and 2021. IPC guidance was implemented in April 2020. There was no difference in the incidence of chemotherapy-induced neutropenia between patients with and without IPC. In patients with IPC, the incidence of FN (9.5%) was lower than that of patients without IPC (27.9%). The hospitalization duration (0.7 ± 1.5 days) and total hospital cost (279.6 ± 42.6 USD) of the IPC group were significantly lower than that of the non-IPC group (2.0 ± 3.8 days and 364.7 ± 271.6 USD, respectively). IPC guidance should be implemented to prevent FN in high-risk patients with breast cancer.

Pre-emptive antifungal therapy versus empirical antifungal therapy for febrile neutropenia in people with cancer.

Intensive cytotoxic chemotherapy for people with cancer can cause severe and prolonged cytopenia, especially neutropenia, a critical condition that is potentially life-threatening. When manifested by fever and neutropenia, it is called febrile neutropenia (FN).Invasive fungal disease (IFD) is one of the serious aetiologies of chemotherapy-induced FN. In pre-emptive therapy, physicians only initiate antifungal therapy when an invasive fungal infection is detected by a diagnostic test. Compared to empirical antifungal therapy, pre-emptive therapy may reduce the use of antifungal agents and associated adverse effects, but may increase mortality. The benefits and harms associated with the two treatment strategies have yet to be determined. OBJECTIVES: To assess the relative efficacy, safety, and impact on antifungal agent use of pre-emptive versus empirical antifungal therapy in people with cancer who have febrile neutropenia. We searched CENTRAL, MEDLINE Ovid, Embase Ovid, and ClinicalTrials.gov to October 2021. We included randomised controlled trials (RCTs) that compared pre-emptive antifungal therapy with empirical antifungal therapy for people with cancer. We identified 2257 records from the databases and handsearching. After removing duplicates, screening titles and abstracts, and reviewing full-text reports, we included seven studies in the review. We evaluated the effects on all-cause mortality, mortality ascribed to fungal infection, proportion of antifungal agent use (other than prophylactic use), duration of antifungal use (days), invasive fungal infection detection, and adverse effects for the comparison of pre-emptive versus empirical antifungal therapy. We presented the overall certainty of the evidence for each outcome according to the GRADE approach. This review includes 1480 participants from seven randomised controlled trials. Included studies only enroled participants at high risk of FN (e.g. people with haematological malignancy); none of them included participants at low risk (e.g. people with solid tumours). Low-certainty evidence suggests there may be little to no difference between pre-emptive and empirical antifungal treatment for all-cause mortality (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.72 to 1.30; absolute effect, reduced by 3/1000); and for mortality ascribed to fungal infection (RR 0.92, 95% CI 0.45 to 1.89; absolute effect, reduced by 2/1000). Pre-emptive therapy may decrease the proportion of antifungal agent used more than empirical therapy (other than prophylactic use; RR 0.71, 95% CI 0.47 to 1.05; absolute effect, reduced by 125/1000; very low-certainty evidence). Pre-emptive therapy may reduce the duration of antifungal use more than empirical treatment (mean difference (MD) -3.52 days, 95% CI -6.99 to -0.06, very low-certainty evidence). Pre-emptive therapy may increase invasive fungal infection detection compared to empirical treatment (RR 1.70, 95% CI 0.71 to 4.05; absolute effect, increased by 43/1000; very low-certainty evidence). Although we were unable to pool adverse events in a meta-analysis, there seemed to be no apparent difference in the frequency or severity of adverse events between groups. Due to the nature of the intervention, none of the seven RCTs could blind participants and personnel related to performance bias. We identified considerable clinical and statistical heterogeneity, which reduced the certainty of the evidence for each outcome. However, the two mortality outcomes had less statistical heterogeneity than other outcomes. For people with cancer who are at high-risk of febrile neutropenia, pre-emptive antifungal therapy may reduce the duration and rate of use of antifungal agents compared to empirical therapy, without increasing over-all and IFD-related mortality; but the evidence regarding invasive fungal infection detection and adverse events was inconsistent and uncertain.

Supportive therapies in the prevention of chemotherapy-induced febrile neutropenia and appropriate use of granulocyte colony-stimulating factors: a Delphi consensus statement

PurposeData indicate that the use of prophylactic granulocyte colony-stimulating factors (G-CSFs) for chemotherapy-induced febrile neutropenia (FN) in routine practice is not consistent with guideline recommendations. The initiative “supportive care for febrile neutropenia prevention and appropriateness of G-CFS use” was undertaken to address the issue of inappropriate prescription of G-CSFs and to improve guideline adherence in the treatment of FN.MethodsIn a two-round Delphi procedure, 36 medical oncologists reviewed clinically relevant recommendations on risk assessment, the appropriate use of G-CSFs, and the prevention of FN based on available literature and individual clinical expertise.ResultsThe consensus was reached on 16 out of 38 recommendations, which are backed by evidence from randomised clinical trials and routine clinical practice. The medical oncologists agreed that the severity of neutropenia depends on patients’ characteristics and chemotherapy intensity, and therefore, the risk of severe neutropenia or FN should be assessed at each chemotherapy cycle so as to initiate prophylaxis with G-CSFs if required. The use of biosimilar G-CSFs, with similar efficacy and safety profiles to the originator biologic, has improved the availability and sustainability of cancer care. The timing of supportive therapy is crucial; for example, long-acting G-CSF should be administered 24–72 h after chemotherapy administration. Each biological agent has a recommended administration dose and duration, and it is important to follow these recommendations to avoid complications associated with under-prophylaxis.ConclusionIt is hoped that these statements will help to increase adherence to guideline recommendations for appropriate G-CSF use and improve patient care.

Meta-Analysis of Same-Day Pegfilgrastim Administration Stratified by Myelotoxic Febrile Neutropenia Risk and Tumor Type.

Pegfilgrastim is recommended to be administered at least 24 hours following the completion of chemotherapy, yet some clinicians use a same-day administration protocol. In this meta-analysis, we compared the incidence of chemotherapy-induced (febrile) neutropenia (CIN/FN) as well as CIN/FN-related chemotherapy disruptions in cancer patients provided with pegfilgrastim same-day vs. next-day. Six databases were searched for comparative studies of same-day vs. next-day pegfilgrastim administration. Fixed or random-effects meta-analyses were conducted to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Thirteen studies were included in this meta-analysis. The FN OR for same-day vs. next-day administration was 1.48 (95% CI = 1.06-2.08) across all cycles, attributable mainly to studies of high FN risk (OR = 2.46, 95% CI = 1.04-5.83) vs. intermediate FN risk regimens (OR = 1.41, 95% CI = 0.95-2.10), and breast cancer (OR = 3.15, 95% CI = 1.24-8.01) vs. non-Hodgkin lymphoma (NHL; OR = 1.48, 95% CI = 0.98-2.23) and gynecologic cancers (OR = 0.64, 95% CI = 0.11-3.85). Where available, ORs for first cycle of chemotherapy, grades 3 and/or 4 CIN, and chemotherapy dose delays or reductions were in line with these findings. In this independent study, same-day pegfilgrastim administration may or may not increase the likelihood of FN, grades 3 and/or 4 CIN, and chemotherapy dose reductions or delays; and this may be a function of the myelotoxicity of the regimens (elevated in high-risk but not intermediate-risk regimens) and tumor type (elevated in breast but not in NHL or gynecologic cancers). With due caution, same-day pegfilgrastim administration may be safe and beneficial in intermediate-risk regimens and selected tumor types.