Prevention Of Febrile Neutropenia Research Articles

Prophylactic pegfilgrastim reduces febrile neutropenia in ramucirumab plus docetaxel after chemoimmunotherapy in advanced NSCLC: post hoc analysis from NEJ051

Ramucirumab plus docetaxel (RD) can cause febrile neutropenia (FN), which frequently requires the prophylactic administration of pegfilgrastim. However, the effects of prophylactic pegfilgrastim on FN prevention, therapeutic efficacy, and prognosis after RD have not been fully evaluated in patients with advanced non-small-cell lung cancer (NSCLC). Two hundred and eighty-eight patients with advanced NSCLC who received RD as second-line therapy after platinum-based chemotherapy plus PD-1 blockade were included. Patients were divided into groups with and without prophylactic pegfilgrastim, and adverse events, efficacy, and prognosis were compared between both groups. Of the 288 patients, 247 received prophylactic pegfilgrastim and 41 did not. The frequency of grade 3/4 neutropenia was 62 patients (25.1%) in the pegfilgrastim group and 28 (68.3%) in the control group (p < 0.001). The frequency of FN was 25 patients (10.1%) in the pegfilgrastim group and 10 (24.4%) in the control group (p = 0.018). The objective response rate was 31.2% and 14.6% in the pegfilgrastim and control groups (p = 0.039), respectively. The disease control rate was 72.9% in the pegfilgrastim group and 51.2% in the control group (p = 0.009). Median progression free survival was 4.3 months in the pegfilgrastim group and 2.5 months in the control group (p = 0.002). The median overall survival was 12.8 and 8.1 months in the pegfilgrastim and control groups (p = 0.004), respectively. Prophylactic pegfilgrastim for RD reduced the frequency of grade 3/4 neutropenia and febrile neutropenia and did not appear to be detrimental to patient outcome RD.Clinical Trial Registration Number: UMIN000042333.

Factors associated with thrombocytopenia in patients treated with pegfilgrastim.

Pegfilgrastim is a long-acting, granulocyte colony-stimulating factor approved in Japan for the prevention of neutropenia caused by antineoplastic agents. Severe thrombocytopenia was reported with pegfilgrastim, however, the factors associated with thrombocytopenia are unclear. This study aimed to explore the factors associated with thrombocytopenia in patients with metastatic castration-resistant prostate cancer treated with pegfilgrastim for primary prophylaxis of febrile neutropenia (FN) with cabazitaxel. This study included metastatic castration-resistant prostate cancer patients who received pegfilgrastim for primary prophylaxis of FN with cabazitaxel. The timing and severity of thrombocytopenia and factors associated with the reduction rate of platelets were examined in patients who received pegfilgrastim for the primary prevention of FN during the first course of cabazitaxel and by multiple regression analysis. Thrombocytopenia was most common within 7 days of pegfilgrastim administration, with 32 cases of grade 1 and 6 cases of grade 2 as per the Common Terminology Criteria for Adverse Events version 5.0. Multiple regression analysis revealed that the reduction rate of platelets after pegfilgrastim administration was significantly positively correlated with monocytes. In contrast, the presence of liver metastases and neutrophils was significantly negatively correlated with the reduction rate of platelets. Thrombocytopenia due to pegfilgrastim administered as primary prophylaxis for FN with cabazitaxel was most likely to occur within one week after pegfilgrastim administration, suggesting that monocytes, neutrophils, and liver metastases were associated with a reduction in platelets.

Prevention of febrile neutropenia in oncological patients: real-world data

Aim. To assess the effect of febrile neutropenia (FN) prophylaxis with granulocyte colony-stimulating factors (G-CSF) in real-world cancer patients.&#x0D; Materials and methods. We conducted a statistical analysis of anonymized medical records collected in the Webiomed platform. Before analysis, the cards were validated by clinical experts. Electronic records were extracted according to two principles: mentioning D70 in the diagnosis or mentioning a chemotherapy regimen associated with a high risk of FN (20%), requiring the primary prevention of neutropenia. Thus, we obtained two datasets comprising 47.085 (590 patients) and 30.523 (398 patients) records, respectively.&#x0D; Results. Based on the analysis results, the most common risk factors for FN development were highly hematologically toxic chemotherapy regimens and elderly age about 50% in the adult population. In both datasets, the number of female patients prevailed (63.7% in dataset 1, 91.2% in dataset 2), so the most common was breast cancer. Less common were cervical cancer, digestive cancer, and lung cancer. Despite the indications for primary prevention of FN, for safety and importance of achieving the planned dose intensity, it was administered in 18.3% of patients in dataset 1 and 2.3% in dataset 2. No FN or G-CSF-related adverse events were reported in patients who received adequate primary prevention.&#x0D; Conclusion. Some issues related to G-CSF administration in cancer patients were identified. We identified the insufficient provision of patients with primary prevention of FN, which negatively affects survival rates and reduces adherence to antitumor therapy. Real-world data demonstrate the efficacy and safety of FN prevention and planned dose intensity maintance in cytotoxic therapy regimens.

Efficacy and Cost-effectiveness of Pegfilgrastim for Preventing Febrile Neutropenia During Docetaxel, Cisplatin, and 5-Fluorouracil Therapy for Esophageal Cancer.

The docetaxel, 5-fluorouracil, and cisplatin (DCF) regimen is an effective form of chemotherapy for advanced esophageal cancer. However, the incidence of adverse events, such as febrile neutropenia (FN), is high. This study retrospectively examined whether pegfilgrastim treatment reduces FN development during DCF therapy. This study evaluated 52 patients who were diagnosed with esophageal cancer and underwent DCF therapy at Jikei Daisan Hospital, Tokyo, Japan, between 2016 and 2020. They were divided into non-pegfilgrastim and pegfilgrastim-treated groups, and side-effects of chemotherapy and cost-effectiveness of pegfilgrastim were examined. Eighty-six cycles of DCF therapy were conducted (33 and 53 cycles, respectively). FN was observed in 20 (60.6%) and seven (13.2%) cases, respectively (p<0.001). The lowest absolute neutrophil count during chemotherapy was significantly lower in the non-pegfilgrastim group (p<0.001), and the number of days until improvement from nadir was significantly shorter in the pegfilgrastim group (9 vs. 11 days; p<0.001). No significant difference was found in the onset of grade 2 or more adverse events by Common Terminology Criteria for Adverse Events. However, renal dysfunction was significantly lower in the pegfilgrastim group (30.7% vs. 60.6%, p=0.038). Hospitalization costs were also significantly lower in this group (692,839 vs. 879,431 Japanese yen, p=0.028). This study revealed the usefulness and cost-effectiveness of pegfilgrastim in prevention of FN in patients treated with DCF.

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.

Developing a standardized approach to prevention and outpatient management of febrile neutropenia.

234 Background: Optimal prevention and safe management of febrile neutropenia (FN) in the outpatient setting, when clinically appropriate, can help to keep vulnerable patients from experiencing severe complications requiring hospitalization. Variation in the prevention and outpatient management of FN was identified as a quality and safety gap by Ontario clinicians. This initiative aimed to facilitate a standardized approach to prevention and outpatient management of FN through the development of practical, evidence-based health-care provider and patient resources. Methods: A clinical practice guideline was developed by a 15-member multidisciplinary Working Group (WG) consisting of physicians, pharmacists, nurses, and administrators who are knowledgeable in the areas of prevention and management of FN. The WG reviewed current relevant international guidelines and available literature on primary and secondary FN prophylaxis and FN management, with an emphasis on the optimal use of granulocyte colony-stimulating factor (G-CSF) and appropriate FN management in the outpatient setting. The 2016 Cancer Care Ontario recommendations on the use of G-CSF were used as a foundation for the prevention of FN content. Key clinical questions were identified by the WG, and content was approached with an Ontario-specific lens. Recommendations were developed using an iterative consensus-building process over six WG meetings. The guideline report was reviewed by external clinical experts who validated final content. Accompanying patient information was informed by health literacy best practices, existing symptom management resources, and input from patient education experts, patients, and caregivers. Results: A user-friendly clinical practice guideline was created. Definitions, risk factors, FN prophylaxis strategies based on risk/treatment intent, and appropriate outpatient management of FN are described. Key clinical questions are reviewed and a total of 25 evidence-informed consensus-based recommendations are presented. The guideline includes FN risk assessment and outpatient FN management algorithms, as well as summaries of available literature and WG discussion. The accompanying patient information explains what neutropenia and neutropenic fever are, lists potential symptoms, and describes management strategies in patient-friendly language. All resources are publicly available on the Ontario Health-Cancer Care Ontario website and have been disseminated broadly to relevant stakeholders via email, social media, and webinars. Conclusions: Review of current evidence and expertise from oncology and infectious disease clinicians resulted in an evidence-informed, consensus-based guideline. This clinical practice guideline and accompanying patient information resource can help to facilitate safe, standardized prevention and appropriate outpatient management of FN.

Decreased incidence of febrile neutropenia in Michigan following masking and social distancing orders for the COVID-19 pandemic: A population based cohort study.

BACKGROUNDIt has been theorized that 75%-80% of febrile neutropenia (FN) is caused by endogenous pathogens, while up to 20% of cases are thought to be caused by a viral infection. It is unknown if precautions such as masking and social distancing reduce the risk of FN in susceptible populations.AIMTo determine whether coronavirus disease 2019 (COVID-19) infection mitigation efforts, namely masking and social distancing, were associated with a reduction in the incidence of FN.METHODSThis was a retrospective population based cohort study comparing the incidence of FN in the 13 mo prior to (Year 0) and 13 mo following (Year 1) the public health executive orders (PHEO) in Michigan. Data was queried for all emergency department (ED) visits from April 1, 2019 to March 31, 2021 from the National Syndromic Surveillance Program, a program which collects data that is voluntarily submitted by approximately 89% of Michigan EDs. The primary study outcome was the incidence of FN as a proportion of ED visits in the 13-mo before and 13-mo after COVID-19 mitigations efforts, namely masking and social distancing. We hypothesized that there would be a significant decrease in the incidence of FN in the period following the PHEO aimed at reducing the spread of the severe acute respiratory syndrome coronavirus 2 virus.RESULTSThere was a total of 8979221 total ED visits captured during the study period. In Year 0 there were 5073081 recorded ED visits and 3906140 in Year 1. There was a significant reduction in the proportion of total ED visits with a diagnosis of FN, decreasing 13.3% across periods (0.15% vs 0.13%, P = 0.036). In patients with a hematologic malignancy a more impressive reduction in the incidence of FN was evident following PHEO (22% vs 17%, P = 0.02).CONCLUSIONWe found a significant association between social distancing and mask guidelines implemented on a large public scale with decreased rates of FN, particularly in those with a hematologic malignancy. These findings may be useful in the design of future research and recommendations regarding the prevention of FN.

Evaluating the safety and effectiveness of PegaGen® (pegfilgrastim) for the prevention of chemotherapy-induced febrile neutropenia: a post-marketing surveillance study.

Phase IV clinical trials are required to evaluate the real-world safety and effectiveness of drugs. This study aimed to evaluate the safety and effectiveness of once-per-cycle administration of PegaGen® (pegfilgrastim, CinnaGen, Iran) in cancer patients. In this open-label, multicenter, prospective, real-world, post-marketing surveillance study, patients with any type of cancer receiving chemotherapy regimens with a high risk of febrile neutropenia (FN) were included if they were prescribed pegfilgrastim for FN prophylaxis. The primary objective of this study was to assess the safety and the secondary objective was to assess the effectiveness of pegfilgrastim in the prevention of FN in cancer patients. A total of 654 patients (51.73 ± 15.12years of age) were enrolled and 3615 cycles of pegfilgrastim injections were recorded. The most common malignancies among the study patients were breast cancer (n = 192, 29.36%), lymphoma (n = 131, 20.03%), and gastric cancer (n = 65, 9.94%). The median (Q1, Q3) number of pegfilgrastim cycles per patient was 6 (4, 7). A single 6mg dose was injected in 99.17% of the cycles. A total number of 816 adverse events (AEs) were reported in 246 patients (37.62%). Bone pain was recorded in 141 patients (21.56%) and in 440 cycles (12.17%). Among all patients, 45 patients (6.88%) experienced FN 51 times, and FN frequency was 1.4% among cycles. Moreover, 14 (2.14%) patients were hospitalized following FN. Antibiotics were administered to 24 patients (3.67%) for FN treatment. The results from this post-marketing surveillance study support the safety and effectiveness of PegaGen® used for the prevention of chemotherapy-induced FN in patients with various types of cancer and treatment regimens. Clinicaltrials.gov identifier: NCT04460079.

A randomized trial of pegylated recombinant human granulocyte-colony stimulating factor to prevent febrile neutropenia in breast cancer after chemotherapy.

e12516 Background: The purpose of this study was to evaluate the incidence of febrile neutropenia (FN) in breast cancer patients with pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF) administration at 48 or 24 hours after chemotherapy for primary prevention. Methods: Patients with stage I-III invasive breast cancer who were scheduled to receive 4 cycles of adjuvant chemotherapy with EC regimen (epirubicin combined with cyclophosphamide) were eligible for this multicenter, open-label, randomized trial. Patients were randomized (1:1) to receive PEG-rhG-CSF (Jinyouli) 48 hours (48h group) or 24 hours (24h group) after the end of each cycle of chemotherapy. The primary endpoint was the incidence rate of FN. The secondary endpoints included the incidence rates of grade 3/4 neutropenia, chemotherapy dose reduction and chemotherapy delay due to neutropenia, antibiotic administration, the pain (bone, muscle, or joint), and the relative dose intensity (RDI) of the chemotherapy. Results: The preliminary results enrolled 197 patients including 96 in the 48h group and 101 in the 24h group. 78.1% of 48h group patients and 73.3% of 24h group patients completed four cycles of chemotherapy. The incidence rates of FN were 2.1% in the 48h group and 4.0% in the 24h group respectively. FN occurred in the first two cycles in the 48h group, while in the 24h group, it occurred only in the first cycles. The incidence rate of grade 3/4 neutropenia was 27.1% in the 48h group and 51.5% in the 24h group respectively. There was no delay in chemotherapy due to neutropenia in the two groups. The incidence rate of chemotherapy dose reduction due to neutropenia was 2.1% in the 48h group and 1.0% in the 24h group respectively. 2 (2.1%) patients in the 48h group and 4 (4.0%) patients in the 24h group received antibiotics. The mean RDI of each cycle of chemotherapy was 91.3% in the 48h group and 91.5% in the 24h group, respectively. The incidence rate of all grades pain (bone, muscle, or joint) was 25.0% in the 48h group, and 20.8% in the 24h group. With regard to 3 or higher grade pain, 1 (1.0%) patient in the 48h group experienced bone pain and 1 (1.0%) patient in the 24h group experienced muscle pain. Conclusions: Preliminary results suggest a similar effect of PEG-rhG-CSF administration at 48 or 24 hours after chemotherapy in primary prevention of FN in breast cancer patients receiving EC chemotherapy regimen. Recruitment is ongoing and updated data will be presented. Clinical trial information: ChiCTR1800019516. [Table: see text]

Real-world effectiveness of prophylactic granulocyte colony-stimulating factor (G-CSF) early (week 1) and late (weeks 2-3) in the cycle for the prevention of febrile neutropenia (FN) among patients (pts) with breast cancer (BC) after high FN–risk chemotherapy (chemo).

599 Background: G-CSF mitigates chemotherapy-induced neutropenia (CIN) and reduces FN risk. G-CSF moves the nadir of absolute neutrophil count (ANC) earlier (to week 1) in the chemo cycle and shortens nadir duration (Crawford, NEJM 1991), suggesting the potential for suboptimal CIN protection early (week 1) in the chemo cycle. The relative FN risk in week 1 vs. weeks 2-3 of the cycle with G-CSF is unknown and was analyzed compared with no G-CSF in the real-world setting with high FN risk chemo. Methods: Using a database of administrative claims representing 100% of fee-for-service Medicare, we analyzed BC pts who initiated docetaxel (T), doxorubicin (A), or cyclophosphamide (C) monotherapy or combination therapy between 01/01/2015 – 12/31/2019. Sample pts included adults aged ≥ 65 years with continuous coverage in Medicare Parts A, B, and D for 6 months before and 20 days after chemo initiation. Pts were categorized as receiving vs. not receiving G-CSF therapy within 3 days after chemo. Rate of FN events starting in week 1 vs. weeks 2-3 in cycle 1 was calculated. We defined FN as an inpatient admission with a primary or secondary diagnosis of neutropenia and measured the interval between chemo initiation and FN admission. Results: Among 18,788 Medicare beneficiaries with BC treated with T, A, and/or C, 72% received G-CSF therapy. More pts receiving G-CSF were treated with ≥ 2 of T, A, and/or C compared to pts who did not receive G-CSF (71% vs. 51%). Overall FN incidence in cycle 1 was significantly lower among pts receiving G-CSF (4.0%; n=546) compared to pts not receiving G-CSF (8.8%; n=462) (p&lt;0.0001). In pts with G-CSF, 81% (440/546) of all 1st-cycle FN events started in week 1 vs. 19% (106/546) in weeks 2-3. In pts not receiving G-CSF, the start of 1st-cycle FN events was more equally distributed: 41% (190/462) started in week 1 vs. 59% (272/462) in weeks 2-3. Results were robust to sensitivity analyses restricted to pts receiving ≥ 2 of T, A, and/or C. The rates of 1st-cycle FN events starting in weeks 1 and 2-3 with and without G-CSF following chemo initiation is shown below. Conclusions: Prophylactic G-CSF was highly effective for the prevention of FN in weeks 2-3, but relatively ineffective in week 1 of cycle 1 in the real-world setting, leaving pts largely unprotected during the first week. This represents an unmet medical need in week 1 of the cycle, despite use of G-CSF. Clinical trial information: NCT03294577. [Table: see text]

Patterns of primary prophylactic granulocyte colony-stimulating factor use in older Medicare patients with cancer receiving myelosuppressive chemotherapy.

Guidelines recommend primary prophylactic (PP) granulocyte colony stimulating factor (G-CSF) for prevention of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy with high risk (HR: > 20%), or intermediate risk (IR:10-20%) of FN and ≥ 1 patient risk factor (e.g., age ≥ 65y). The current retrospective cohort study describes patterns of PP-G-CSF in older Medicare patients undergoing myelosuppressive chemotherapy with HR/IR of FN. Patients aged ≥ 66y initiating chemotherapy regimens with HR/IR of FN to treat breast, colorectal, lung, or ovarian cancer, or Non-Hodgkin's Lymphoma were selected using Medicare 20% sample (2013-2015) and 100% cancer patient (2014-2017) data. PP-G-CSF use was identified in the first cycle. Timing of pegfilgrastim pre-filled syringe (PFS) administration, proportion of patients completing all cycles (adherence) with pegfilgrastim PFS or on-body injector (OBI), and duration of short-acting G-CSF (sG-CSF) was described across all cycles. Of 64,893 patients receiving HR/IR for FN, 71% received HR and 29% IR regimens. Overall, PP-G-CSF use in the first cycle was 53% (HR: 74%; IR: 44%) and varied across cancers. Adherence with pegfilgrastim was slightly higher among OBI initiators (78%) than PFS (74%). Number of PP-sG-CSF administrations (mean [SD]) per cycle was 5.1 (SD: 2.7) overall, 5.4 (2.6) for HR, and 4.9 (2.7) for IR. Despite cancer treatment guidelines recommending PP-G-CSF use to reduce risk of FN associated with HR and IR (with ≥ 1 patient risk-factor) regimens, PP-G-CSF remains underutilized in older patients, across cancer types and regimens. Opportunities exist for improvement in use of PP-G-CSF.

Effect of early granulocyte-colony-stimulating factor administration in the prevention of febrile neutropenia and impact on toxicity and efficacy of anti-CD19 CAR-T in patients with relapsed/refractory B-cell lymphoma

Chimeric Antigen Receptor T cells (CAR-T) are an outbreaking treatment option for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the most common specific toxicities, while severe neutropenia and infections are often observed as well. From March 2020, early G-CSF prophylaxis at day (D) two post-infusion was systematically proposed. We then compared patients treated before that date who did not receive G-CSF or who received late (after D5) G-CSF as control group. Patients administered with early G-CSF had similar duration of grade 4 neutropenia but significantly decreased incidence of febrile neutropenia (58% versus 81%, p = 0.018). Similar rate of toxicities was observed, including overall and grade 3-4 CRS (p = 0.93 and p = 0.28, respectively), and overall and grade 3-4 ICANS (p = 0.62 and p = 0.88, respectively). We observed no difference in the quality of CAR T-cells expansion (p = 0.79, %Cmax), nor in response rate (best ORR, 57.6% vs 61.8%, p = 0.93), nor survival even in a group of patients adjusted by a propensity score. In conclusion, early G-CSF administration was safe and effective in reducing febrile neutropenia without impact on toxicities nor on anti-lymphoma activity of CAR-T.

Comprehensive evaluation of risk factors for the development and complications of chemotherapy-induced febrile neutropenia

Febrile neutropenia is a serious adverse effect of chemotherapy. It can lead to complications and death, as well as delays in treatment, chemotherapy dose reductions, compromised treatment efficacy, and reduced survival. The assessment of the patient-related risk factors plays a significant role in the prevention of febrile neutropenia and its complications. In the case of intermediate-risk chemotherapy, the patient-related factors contribute to the estimation of an overall febrile neutropenia risk as well as to timely planning of primary prophylaxis using growth factors. Patients presenting with febrile neutropenia undergo a detailed initial risk assessment for serious complications so that an appropriate treatment can be selected. Recommendations given by the guidelines outline the classification of and risk factors for febrile neutropenia complications. The use of patient-related factors and validated tools for the risk assessment of complications makes it possible to optimize the treatment for each patient and to reduce the risk of morbidity and mortality due to febrile neutropenia.

Febrile neutropenia prevention with G-CSF in patients receiving chemotherapy

Febrile neutropenia prevention with G-CSF in patients receiving chemotherapy

Pegfilgrastim Prophylaxis Is Effective in the Prevention of Febrile Neutropenia and Reduces Mortality in Patients Aged ≥ 75 Years with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: A Prospective Cohort Study.

PurposeFebrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP).Materials and MethodsWe conducted a prospective cohort study to evaluate the effectiveness of pegfilgrastim prophylaxis in DLBCL patients receiving R-CHOP, and we compared them with the PROCESS cohort (n=485).ResultsSince January 2015, 986 patients with DLBCL were enrolled. Pegfilgrastim was administered at least once in 930 patients (94.3%), covering 90.3% of all cycles. FN developed in 137 patients (13.9%) in this cohort (23.7% in the PROCESS cohort, p < 0.001), and 4.2% of all cycles (10.2% in the PROCESS cohort, p < 0.001). Dose delay was less common (≥ 3 days: 18.1% vs. 23.7%, p=0.015; ≥ 5 days: 12.0% vs. 18.3%, p=0.023) in this cohort than in the PROCESS cohort. The incidence of TRM (3.2% vs. 5.6%, p=0.047) and infection-related death (1.8% vs. 4.5%, p=0.004) was lower in this cohort than in the PROCESS cohort. The 4-year overall survival (OS) and progression-free survival (PFS) rates of the two cohorts were not different (OS: 73.0% vs. 71.9%, p=0.545; PFS: 69.5% vs. 68.8%, p=0.616). However, in patients aged ≥ 75 years, the 4-year OS and PFS rates were higher in this cohort than in the PROCESS cohort (OS: 49.6% vs. 33.7%, p=0.032; PFS: 44.2% vs. 30.3% p=0.047).ConclusionPegfilgrastim prophylaxis is effective in the prevention of FN and infection-related death in DLBCL patients receiving R-CHOP, and it also improves OS in patients aged ≥ 75 years.

Assessment of Micafungin Dosage Regimens in Patients with Cancer Using Pharmacokinetic/Pharmacodynamic Modeling and Monte Carlo Simulation.

Micafungin is widely used for invasive candidiasis, especially in critically ill patients and those with cancer, and for empirical antifungal therapy in patients with neutropenic fever. This is the first study to investigate the pharmacokinetics and disposition parameters of micafungin in patients with cancer. In this observational pharmacokinetic study, blood samples were collected and analyzed using high-performance liquid chromatography. Pharmacokinetic parameters were estimated using Monolix 4.4 software. The plasma micafungin concentrations were measured in a total of 133 samples from 19 patients. In the final two-compartment model with linear elimination, the estimated micafungin clearance (CL) was significantly higher in patients with cancer than in those without cancer (1.2 vs. 0.6 L/h, p = 0.012), whereas other parameters did not significantly differ between the two groups. Aspartate and alanine transaminases and body weight significantly influenced micafungin CL in patients, with and without cancer. Overall, the probability of target attainment increased with increasing doses and decreased with higher MICs in both groups. In simulations, the patients without cancer achieved higher pharmacokinetic/pharmacodynamic targets with a 90% probability for all simulated doses, compared to the patients with cancer. Micafungin demonstrated dose-proportional linear pharmacokinetics in both the patients with and those without cancer. The estimated micafungin CL was significantly higher in patients with cancer, suggesting a need for increased dosage, especially for Candida spp. with high MICs, in these patients. Further studies should assess the efficacy and optimum dosage of micafungin for the treatment and prevention of febrile neutropenia (FN) in patients with cancer.

Real-world utilization and costs with biosimilar and reference filgrastim in patients with breast cancer receiving myelosuppressive chemotherapy in a community oncology setting from 2015 to 2017.

57 Background: Biosimilars have potential to reduce healthcare costs and increase access in the United States, but lack of uptake has contributed to lost savings. Filgrastim-sndz was the first FDA-approved biosimilar, and much can be learned by evaluating its uptake. In February 2016, the US Oncology Network converted to filgrastim-sndz as its short-acting granulocyte colony-stimulating factor (GCSF) of choice for prevention of febrile neutropenia (FN) following myelosuppressive chemotherapy (MCT). To understand utilization and cost patterns, this study analyzes real-world data of GCSFs within a community oncology network during the initial period of conversion to the first biosimilar available in the US. Methods: This descriptive retrospective observational study used electronic health record data for female breast cancer (BC) patients receiving GCSF and MCT at high risk of FN. Patient cohorts were defined by first receipt of either filgrastim or filgrastim-sndz during the 410 days before and after biosimilar conversion. Healthcare resource utilization (HCRU) and costs for GCSF and complete blood counts (CBC) were collected at GCSF initiation through the earliest of 30 days following end of MCT, loss to follow up, death, or data cutoff. Results: 146 patients were identified: 81 (55.5%) filgrastim and 65 (44.5%) filgrastim-sndz. No directional differences existed in baseline characteristics between the cohorts. Higher proportions of filgrastim-sndz patients received dose-dense MCT (33.8% vs 22.2%). Time trends show an initial spike in HCRU and cost for filgrastim-sndz patients after formulary conversion, which subsequently decreased and converged to that of the filgrastim cohort after 12 months. When aggregated, the overall median total administration counts, per patient per month (PPPM) and dosage, were marginally higher for filgrastim-sndz (5 vs 3; 2.9 vs 1.4; 1920 vs 1440 mcg, respectively). Median PPPM costs were higher for filgrastim-sndz ($803 vs $545). Median CBC utilization and costs were higher for filgrastim-sndz (2.8 vs 2.5; $28 vs $23, respectively). Conclusions: This study provides insight into real-world HCRU and cost patterns after formulary conversion to a biosimilar for BC patients receiving MCT and GCSF. As a descriptive study, causal inferences cannot be made and an underlying effect from index chemotherapy cannot be excluded. Convergence of HCRU and costs after 12 months suggests that overall results may be driven by behavior at initial formulary switch. Since filgrastim-sndz was the first US biosimilar approved, the uptake may be indicative of an experience with biosimilar acceptance in general. Future real-world studies of biosimilars must consider inconsistent utilization and practice trends during the time frame directly following formulary conversion.

The importance of the prevention of treatment induced neutropenia in patients with malignant neoplasms of the head and neck

Hematological toxicity is the most common complication of chemotherapy. The most dangerous manifestation of hematological toxicity is febrile neutropenia (FN). FN reduces survival, increases the risk of death, the frequency of infectious complications, hospitalizations, the cost of treatment. The risk of FN should be assessed before the beginning of the therapy, using the general algorithm from the protocol to prevent FN applying the granulocyte colony-stimulating factors (G-CSF). G-CSF for the prevention is required throughout all cycles of myelosuppressive therapy. For the prevention of FN, the most effective is the use of PEGylated G-CSF. Patients with head and neck squamous cell carcinoma, receiving the TPF or DCF regimen, combined with docetaxel and cisplatin, are included in the group of routine primary prophylaxis for neutropenia. In case of developing 34 grade FN in these patients, the use of PEGylated G-CSF (empegfilgrastim) is preferable.

Utility of prophylactic antibiotics for preventing febrile neutropenia during cabazitaxel therapy for castration-resistant prostate cancer

The aim was to investigate the efficacy of prophylactic antibiotics for the prevention of febrile neutropenia (FN) during cabazitaxel therapy for castration-resistant prostate cancer (CRPC) with G-CSF. We retrospectively studied 443 cycles of cabazitaxel therapy given to 56 patients with CRPC at Keio University Hospital between May 2012 and August 2018. Statistical analysis was conducted to determine whether the combination of prophylactic G-CSF and antibiotics was more effective in preventing FN, compared with prophylactic G-CSF alone. Prophylactic PEG-G-CSF or G-CSF was administered in all 443 cycles. Only fluoroquinolones were used as prophylactic antibiotics and were administered in 328 cycles (74.0%). FN occurred in 5 cycles (1.1%). Prophylactic antibiotics were administered in 327 cycles (74.6%) in the FN-negative group and in only 1 cycle (20.0%) in the FN-positive group. Chi-square test indicated the incidence of FN was significantly lower in the group that received prophylactic antibiotics compared with the group that did not receive prophylactic antibiotics (P = 0.017). Compared with prophylactic G-CSF alone, prophylactic G-CSF and antibiotics significantly suppressed the occurrence of FN.

Change in Body Weight and Serum Albumin Levels in Febrile Neutropenic Lung Cancer Patients.

Although advances have been made in the treatment and prevention of febrile neutropenia (FN) in cancer patients treated with chemotherapy, it is still a complication that requires clinical attention. Impaired nutritional status in patients who develop FN can affect the continuation of cancer treatment, but it has not been investigated. We conducted a retrospective longitudinal study in order to clarify (1) if body weight and serum albumin levels change in lung cancer patients who do and do not develop FN, and (2) if these indicators are more likely to worsen in patients with FN than in patients without FN. Patients undergoing cytotoxic chemotherapy between January 2011 and June 2020 were consecutively included in the study. Changes in body weight and serum albumin levels were investigated in a case–control study of patients with FN, and control patients without FN who were matched by age, gender, histopathology, and stage of lung cancer, at a ratio of 1:2. During the study period, 226 patients received cytotoxic chemotherapy. Among those, 33 (14.6%) patients developed FN during the first course of cytotoxic chemotherapy. We found a more pronounced decrease in both body weight and serum albumin level at four weeks after the initiation of chemotherapy in FN patients. In order to safely administer effective chemotherapy, medical staff need to pay close attention to the nutritional status of patients receiving chemotherapy.