Use Of Pegfilgrastim Research Articles

Cost of Pegfilgrastim for the Prophylaxis of Chemotherapy-induced Febrile Neutropenia in Patients with Breast Cancer Receiving Perioperative Chemotherapy in Daily Practice in Japan: A Posthoc Analysis in a Single-center Retrospective Study.

This study aimed to estimate the medical costs associated with febrile neutropenia (FN) prophylaxis with pegfilgrastim and evaluate its impact on survival outcomes in daily practice in Japan. In this single-center retrospective study, we obtained data from 296 Japanese patients with breast cancer receiving fluorouracil, epirubicin, and cyclophosphamide (FEC)-100 chemotherapy; the patients were divided into the pegfilgrastim and non-pegfilgrastim groups. We analyzed the median costs of chemotherapy, drugs for all adverse events (AEs) and FN, and hospitalization due to FN. We also assessed the survival outcomes. The pegfilgrastim group showed a significantly higher median total cost (JPY 872320.0 vs. JPY 466715.0, p<0.001). This difference was associated with the prophylactic use of pegfilgrastim. The median costs of the drugs for all AE treatments were JPY 9030.4 and JPY 24690.6, with the non-pegfilgrastim group showing a significantly higher cost (p<0.001). In 11 patients hospitalized for FN management, no significant difference in hospitalization cost was observed between the pegfilgrastim and non-pegfilgrastim groups (JPY 512390.0 vs. JPY 307555.0, p=0.102). No significant difference in the 3-year overall survival was observed between the pegfilgrastim and non-pegfilgrastim groups (79.9% vs. 88.3%, p=0.672). In this study, although the total medical cost in daily practice increased because of primary prophylaxis with pegfilgrastim, the 3-year overall survival was not impacted by the use of pegfilgrastim. Our study data suggested that the primary prophylaxis pegfilgrastim should be used during FEC-100 chemotherapy based on the patient-related FN risk factors, instead of routine use.

A retrospective single institutional analysis of outpatient chemotherapy in patients with cancer during the COVID-19 pandemic.

Providing treatment to patients with cancer, even during the coronavirus disease (COVID-19) pandemic, is essential. In collaboration with infectious disease specialists, we established guidelines for the management of patients with cancer receiving ambulatory treatment during the pandemic on April 8, 2020. This study examined the practice and management of ambulatory chemotherapy under emergency conditions. Following the guidelines, our Breast and Medical oncology department developed a chemotherapy strategy for the phases. Additionally, to distinguish fever during chemotherapy, we developed a flow chart for fever. As part of a fact-finding survey, the status of outpatient chemotherapy was investigated: (1) whether there was any change in the number of chemotherapies before and after the declaration of a state of emergency by the Tokyo Metropolitan Government and (2) the frequency and severity of febrile neutropenia (FN) cases. Compared to before the first declaration of the state of emergency, the number of chemotherapies decreased except after the declaration, but no decrease was observed during the rest of the period; no difference was observed in the frequency or severity of FN outbreaks or in the use of pegfilgrastim for primary prevention before and after the epidemic. With appropriate treatment guidelines, routine chemotherapy can be performed in an outpatient setting during an outbreak.

Abstract PO1-12-06: Is it appropriate to select patients for primary prophylactic use of pegfilgrastim based on the risk of febrile neutropenia?

Abstract Background: Febrile neutropenia (FN), a major hematologic adverse event in perioperative chemotherapy for breast cancer, is more prevalent among Asians than in Caucasian populations. Four main guidelines, i.e., ASCO, EORTC, NCCN, and ESMO, provide recommendations regarding the appropriate use of hematopoietic growth factors. These guidelines recommend primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) based on the estimated incidence of FN, primarily defined by the chemotherapy regimen. G-CSF administration is recommended when the incidence of FN is ≥20% or 10–20% with risk(s). However, the incidence of FN varies depending on the trial and design, and patient-specific risk factors for FN remain unclear. We previously performed a multicenter prospective cohort study in Japan, the CSPOR-BC FN study, evaluating the incidence of FN during perioperative chemotherapy for breast cancer. Herein, we conducted an additional analysis to explore thresholds of patient-specific risk factors for FN that could be evaluated before chemotherapy. We analyzed the risk factors for FN and verified the appropriateness of patient selection for prophylactic G-CSF administration. Methods: The previously reported CSPOR-BC FN study (PubMed ID=33631458) consecutively enrolled 1005 patients with stage I–III breast cancer between August 2015 and July 2017. In the current additional analysis, we intended to have 477 patients in the visiting group that evaluated true-FN, defined as ≥37.5℃ and grade 4 neutropenia. Multivariate analysis of risk factors for FN was performed, followed by the determination of cutoff values for age and pretreatment absolute neutrophil count (ANC) as risk factors. Results: Chemotherapy regimens administered were FEC (fluorouracil, epirubicin, and cyclophosphamide) in 170 patients (36%), E(A)C (epirubicin (doxorubicin) + cyclophosphamide) in 165 patients (35%), and TC (docetaxel + cyclophosphamide) in 142 patients (30%). The incidence of FN was 28.7% (N = 137). To evaluate the risk factors for FN, we predefined regimens, age, performance status (PS), stage, chemotherapy or radiotherapy history, infectious wounds, open wounds, ANC, and renal and liver dysfunction as potential risk factors. Multivariate analysis of risk factors for FN identified regimen (TC), age (≥65), low pretreatment ANC, treatment setting, and no primary pegfilgrastim prophylaxis as significant risk factors. Two patient-specific risk factors (age and pretreatment ANC) were analyzed. Logistic regression analysis revealed that age≥65 years was a significant risk factor (odds ratio=2.24, 95% confidence interval: 1.34–3.75). Applying a cutoff of 65 years (age) to predict FN, the sensitivity and specificity were 28.4 and 83.8%, respectively, which were inaccurate. Despite applying a cutoff of 67 years optimized from the receiver operating characteristic (ROC) curve, the sensitivity (22.4%), specificity (90.7%), and area under the curve (0.519) indicated low discrimination for predicting FN. The incidence of FN by age group was as follows: &amp;lt; 45 years, 30.8%; 45–55 years, 26.4%; 55–64 years, 20.9%; ≥65 years, 39.6%. Additionally, applying a cutoff of 2436/µL (pretreatment ANC) optimized from the ROC curve, the observed sensitivity (27.6%) and specificity (83.8%), and area under the curve (0.558) also indicated low discrimination for predicting FN. The incidence of FN by stratum of pretreatment ANC was as follows: &amp;lt; 2000, 33.3%; 2000–3000, 30.7%; 3000–4000, 29.9%; and &amp;gt;4000, 24.6. Accordingly, setting a cutoff value to predict FN incidence using age and/or pretreatment ANC was deemed inappropriate. Conclusion: Selecting patients for primary prophylactic G-CSF based on the existing FN risk can be challenging. Primary prophylactic G-CSF would be considered for every patient undergoing perioperative chemotherapy for breast cancer, especially Asians. ROC curve for FN and age. The AUC was 0.519. ROC curve for FN and neutrophil count. The AUC was 0.558. Citation Format: Kazutaka Narui, Takashi Ishikawa, Ikumi Takashima, Kosuke Kashiwabara, Yukari Uemura, Yuichiro Kikawa, Naruto Taira, Hirofumi Mukai. Is it appropriate to select patients for primary prophylactic use of pegfilgrastim based on the risk of febrile neutropenia? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-12-06.

Docetaxel, cisplatin, and fluorouracil with pegfilgrastim on day 3 as neoadjuvant chemotherapy for esophageal cancer.

A high risk of febrile neutropenia (FN) from neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer has been reported. The optimal timing of prophylactic use of pegfilgrastim remains to be elucidated. To evaluate the effect of pegfilgrastim administered on day 3, we conducted a feasibility study. Chemotherapy consisted of intravenous administration of docetaxel (70 mg/m2 per day) and cisplatin (70 mg/m2 per day) on day 1 and continuous infusion of 5-fluorouracil (750 mg/m2 per day) on days 1-5. Pegfilgrastim was given as a single subcutaneous injection at a dose of 3.6 mg on day 3 during each treatment course. This regimen was repeated every 3 weeks for up to a maximum of three courses. Prophylactic antibiotics were not needed but were allowed to be given at the discretion of the physician. The primary endpoint was the incidence of FN. Twenty-six patients were administered DCF in combination with pegfilgrastim on day 3. After the first course of DCF, 10 out of 26 patients (38.5%) experienced grade 4 neutropenia, and two patients (7.7%) experienced FN. Of the 14 patients who did not receive prophylactic antibiotics, four had grade 4 neutropenia, including two who developed FN. On the contrary, of the 12 patients who received prophylactic levofloxacin, six had grade 4 neutropenia, but no cases of FN were observed. Administration of pegfilgrastim on day 3 was not sufficient to prevent FN due to DCF treatment, and prophylactic administration of both pegfilgrastim and antibiotics could be a solution.

The Combination of Pegfilgrastim and Filgrastim Improves the Outcomes of Mobilization and Engraftment after Transplantation of Autologous Hematopoietic Stem Cells for the Treatment of Lymphoma

BACKGROUND : Hematopoietic stem cell transplantation (HSCT) is broadly utilized for the treatment of lymphoma. Autologous peripheral blood stem cell (PBSC) transplantation (ASCT) requires mobilization of hematopoietic stem cell/ hematopoietic progenitor cell (HSC/HPC) in peripheral blood (PB) to collect HSCs. The high mobilization failure rate with the mobilization strategy of combining chemotherapy and filgrastim (rhG-CSF, recombinant human granulocyte colony-stimulating factor) in ASCT is one of the unresolved issues. Whether the combination of polyethylene glycol filgrastim [pegfilgrastim (PEG-FIL), PEG-rhG-CSF] and filgrastim (FIL) improves the mobilization success rate and the timing of combination therapy has not been studied. METHODS: To test the hypothesis that the combination of pegfilgrastim and filgrastim schedule has superiority, we retrospectively investigated a cohort of 107 lymphoma patients who received auto-HSCT and collection in the First Hospital of Jilin University from Jan 1st 2015 to Dec 1st 2022. These patients were categorized into PEG+FIL group and FIL group. The group of PEG+FIL received pegfilgrastim (9 mg) on the third day of the chemotherapy, followed by filgrastim (10 μg/kg/day) based on the counts of peripheral blood stem cells (PBSC). The group of FIL received filgrastim 10 μg /kg/day depending on the number PBSCs. Demographic information, laboratory results, and treatment plans were collected for these two groups of patients. RESULTS：We compared their mobilization efficacy (mononuclear cell [MNC] and CD34 + cell counts) and transplantation efficacy (days to leukocyte and platelet recovery post-transplantation). Successful ASCT mobilization was achieved in 93 patients (86.9%), with the PEG+FIL group exhibiting a higher success rate compared to the FIL group (89.2% [58/65] vs. 83.3% [35/42], p = 0.032). The PEG+FIL group also demonstrated significantly higher CD34+ cell counts [MNC: 8.9 (6.9, 11.2) vs. 7.8 (6.2, 9.8) × 10 8 cells/kg, p = 0.024; CD34 + cell count: 7.5 (5.6, 13.0) vs. 4.9 (3.2, 9.2) × 10 6 cells/kg, p = 0.008] and a lower incidence of neutropenic fever compared to the FIL group (11.8% vs. 24.3%, p = 0.038). The PEG+FIL group also demonstrated a shorter mean leukocyte recovery time in autologous stem cell transplantation than the FIL group (10.02 ± 0.73 vs. 10.9 ± 1.1 days, p &amp;lt; 0.001). To delve deeper into the safety considerations of both groups, we evaluated the advantages of each regimen and the methodologies for selecting time windows. A bone marrow aspiration and biopsy were performed on all patients before stem cell collection. Among 18 patients who had a hematopoietic area less than 30% and a fat area greater than 40%, 10 were in the PEG+FIL group and 8 in the FIL group. For patients who required only one collection, the durability was 80% in the PEG+FIL group compared to 0% in the FIL group (p &amp;lt; 0.01), indicating a superior recommendation for patients with a bone marrow hematopoietic area of less than 30%. In the PEG+FIL group, monitoring was carried out for PB CD34 + percentage and WBC count following pegfilgrastim administration, with subsequent computation of CD34 + cells in PB. Filgrastim administration was found to be optimal 5-6 days post-pegfilgrastim administration. CONCLUSIONS: In conclusion, relative to conventional filgrastim mobilization, the conjunctive use of pegfilgrastim and filgrastim demonstrates superior efficacy, non-inferior safety during ASCT. The schedule enhanced the the outcomes of mobilization in the patients of less hematopoietic area. KEY WORDS: Pegylated recombinant human granulocyte-stimulating factor (pegfilgrastim, PEG-rhG-CSF), recombinant human granulocyte-colony stimulating factor (filgrastim, rhG-CSF), lymphoma, hematopoietic stem cell transplantation (HSCT) autologous hematopoietic stem cell mobilization.

An observational, prospective, open label, multicenter study to evaluate the safety and effectiveness of pegfilgrastim as secondary prophylaxis to decrease the incidence of febrile neutropenia in Korean female patients with breast cancer

PurposePegfilgrastim is a widely used long-acting granulocyte colony-stimulating factor (G-CSF) that prevents febrile neutropenia (FN) in patients with breast cancer receiving chemotherapy. This study aimed to evaluate the incidence of chemotherapy-related FN events and other adverse events (AEs) during chemotherapy in Korean patients with breast cancer treated with pegfilgrastim as secondary prophylactic support. Materials and methodsThis was a multicenter, open-label, prospective, observational study. A total of 1255 patients were enrolled from 43 institutions. The incidence of FN was evaluated as the primary endpoint. The secondary endpoints included (1) incidence of bone pain, (2) proportion of patients with a relative dose intensity (RDI) of ≥85%, and (3) proportion of patients with AE. ResultsPegfilgrastim administration reduced FN by 11.8–1.6%. The highest incidence of bone pain was observed at the time point of the 1st day after the administration and mild bone pain was the most common of all bone pain severity. The mean RDI was 98.5 ± 7.3%, and the proportion of the patients with and RDI≥85% was 96.9% (1169/1233). AEs were reported in 52.6% of the patients, and serious drug reactions occurred in only 0.7%. ConclusionThe use of pegfilgrastim as secondary prophylaxis was effective and safe for preventing FN in patients with breast cancer who were treated with chemotherapy.

The Theoretical Role for Radiotherapy in Patients with Diffuse Large B-Cell Lymphoma: A Secondary Analysis of a Prospective Randomized Controlled Trial.

The role of radiotherapy (RT) for diffuse large B-cell lymphoma (DLBCL) is unclear. In patients treated with upfront chemotherapy for DLBCL, indications for RT are often considered to be bulky (7.5 cm +) or extranodal disease. This is thought to improve outcomes through improvement in local control. Many trials call into question the actual benefit of RT. Alliance/CALGB 50303 was a randomized phase III trial comparing two chemotherapy regimens for the treatment for DLBCL in which no patients were to receive RT. Our objective was to assess the theoretical impact of RT by assessing outcomes of trial patients. This secondary analysis was performed using PET/CT images and data from the NCTN/NCORP Data Archive of the National Cancer Institute. Data were originally collected on the Alliance/CALGB 50303 (NCT00118209) clinical trial. Of the 524 registered patients, data and images for 155 patients were available. Two investigators measured the largest sites of nodal involvement on PET/CT and the average was calculated-the largest was used to determine bulky disease. Bulk was defined as nodal disease with maximum diameter greater than or equal to the threshold. Thresholds (in cm) examined included: 5, 6, 7, 7.5, 8, 9, and 10. PFS was estimated for patients with versus without bulky disease and compared using the log-rank test. Of the 155 evaluable pre-treatment PET/CT image sets, 135 patients had measurable nodal disease. Fifteen patients who did not complete treatment per protocol and four patients with mediastinal B-cell lymphoma were excluded. Of the 116 analyzed patients, 45% had stage IV disease, 88% had an ECOG performance status of 0-1, and one had double-hit lymphoma. IPI was 0-2 in 62% and 3-5 in 38%. Chemotherapy was R-CHOP in 61 and DA-R-EPOCH in 55. Best response was CR in 84 patients (73%), PR in 30 (26%) and SD in 1 (1%). The median follow-up was 5 years and 32 PFS events were observed. Bulky disease was associated with elevated LDH at diagnosis (using 7.5 cm threshold: LDH elevated in 72% with bulky disease v. 40% with non-bulky, p< 0.01) and more frequent use of pegfilgrastim (51% v. 31%, respectively, p = 0.04). Overall, the 5-year PFS rate was 72.3% (95% CI 64.1-81.4). Using a 7.5 cm threshold, 5-year PFS was 62.7% in patients with bulk versus 79.3% in those without (p = 0.14). There were no significant PFS differences (p>0.05) observed at any threshold. The 5-year OS was 86.4% (95% CI 80.2-93.1); no differences in OS by bulk using any threshold were observed. In this secondary analysis of a phase III randomized trial of chemotherapy alone for DLBCL, initial bulk was not shown to be significantly associated with outcomes. Prospective data comparing consolidative RT versus no RT are necessary to determine optimal treatment paradigms.

Abstract P4-03-33: A Population-based Analysis of Prophylactic G-CSF Biosimilar and Originator Administration over time among Patients Diagnosed with Breast Cancer

Abstract A Population-based Analysis of Prophylactic G-CSF Biosimilar and Originator Administration over time among Patients Diagnosed with Breast Cancer Pawloski PA1, McDermott CL2, Vazquez Benitez G1, DeFor T1, Mendelsohn A3, Marshall J3, Moyneur E4, Lockhart CM2; on behalf of the G-CSF Comparative Effectiveness Research Team. 1HealthPartners Institute, Bloomington MN USA 2Biologics and Biosimilars Collective Intelligence Consortium, Alexandria VA USA 3Harvard Pilgrim Healthcare Institute, Boston MA USA 4StatLog, Montreal QC Canada Objectives: To characterize G-CSF product use, including product switching, among patients diagnosed with breast cancer in the Biologics and Biosimilars Collective Intelligence Consortium’s (BBCIC) Distributed Research Network (DRN). Methods: A retrospective analysis of electronically extracted insurance claims from 2015-2019 at 4 Research Partner Sites was conducted. Patients aged &amp;gt;=20 years with a diagnosis of breast cancer who received chemotherapy associated with a risk of febrile neutropenia (FN) risk per National Comprehensive Cancer Network guidelines and any prophylactic granulocyte-colony stimulating factor (G-CSF), defined as before day 2 of the first cycle of chemotherapy were included. Results: A total of 11,788 patients were included; 89 (0.8%) were male sex per insurance records. The age distribution was 5,743 (49%) 50-64 years; 4,296 (36%) 20-49 years, and 1749 (15%) 65+ years. Chemotherapy regimens included cyclophosphamide/doxorubicin (n=7,377), carboplatin/docetaxel/trastuzumab/pertuzumab (n=1,862), cyclophosphamide/docetaxel (n=1,383), carboplatin/docetaxel/trastuzumab (n=430), cyclophosphamide/docetaxel/doxorubicin (n=147), and docetaxel/trastuzumab/pertuzumab (n=128). Overall, 218 patients (1.8%) developed FN during the first chemotherapy cycle. G-CSF utilization was pegfilgrastim 10,895 (92%), pegfilgrastim-cbqv 315 (3%), pegfilgrastim-jmdb 225 (2%), filgrastim 156 (1%), filgrastim-sndz 118 (1%), tbo-filgrastim 46 (&amp;lt; 1%), a combination of pegfilgrastim+filgrastim 26 (&amp;lt; 1%), and a combination of filgrastim+biosimilar 7 (&amp;lt; 1%) received. A total of 10,953 (93%) patients received high-risk chemotherapy and G-CSF utilization was 10,162 (93%) pegfilgrastim, 288 (3%) pegfilgrastim-cbqv, 200 (2%) pegfilgrastim-jmdb, 132 (1%) filgrastim, 101 (&amp;lt; 1%) filgrastim-sndz, 40 (&amp;lt; 1%) tbo-filgrastim, and 30 (&amp;lt; 1%) combination of products. Eight hundred fifteen (7%) patients received intermediate-risk chemotherapy and G-CSF utilization was, 716 (88%) pegfilgrastim, 27 (3%) pegfilgrastim-cbqv, 25 (3%) pegfilgrastim-jmdb, 23 (3%) filgrastim, 16 (2%) filgrastim-sndz, 5 (&amp;lt; 1%) tbo-filgrastim, and 3 (&amp;lt; 1%) combination. Twenty patients received low risk chemotherapy and of those 17 (85%) received pegfilgrastim. In 2019, the first full year of pegfilgrastim biosimilar availability, pegfilgrastim use was 76% pegfilgrastim, 13% pegfilgrastim-cbqv, and 9% pegfilgrastim-jmdb. Most patients who received a second cycle of chemotherapy received the same G-CSF product in the second cycle, specifically 67% received filgrastim, 71% tbo-filgrastim, 73% filgrastim-sndz, 96% pegfilgrastim, 84% pegfilgrastim-cbqv, and 81% pegfilgrastim-jmdb. Conclusions: The most common chemotherapy agents included cyclophosphamide, carboplatin, doxorubicin, docetaxel, or pertuzumab. Pegfilgrastim biosimilar uptake occurred following market availability. Within each G-CSF product, most patients received the same product during the second cycle of chemotherapy rather than switching products. Citation Format: Pamala A. Pawloski, Cara L McDermott, Gabriela Vazquez Benitez, Terese DeFor, Aaron B. Mendelsohn, James Marshall, Erick Moyneur, Catherine Lockhart. A Population-based Analysis of Prophylactic G-CSF Biosimilar and Originator Administration over time among Patients Diagnosed with Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-33.

Dose reduction of docetaxel avoids the usage of pegfilgrastim in docetaxel plus ramucirumab therapy for recurrent nonsmall cell lung cancer.

Pegfilgrastim is recommended in docetaxel plus ramucirumab (DTX + RAM) therapy for recurrent nonsmall cell lung cancer (NSCLC) because of the associated frequency of febrile neutropenia (FN). However, the FN occurs less frequently when the dose of DTX is reduced because of other adverse events, such as appetite loss and oral mucositis. Twenty-two patients with recurrent NSCLC who received DTX + RAM therapy at the Hiroshima Prefectural Hospital. The cut-off value which is the most unlikely to cause FN without the combined use of pegfilgrastim was set using a receiver operating characteristic (ROC) curve. This was created according to the dose of DTX and the presence or absence of the onset of FN. We compared the incidence of FN when a DTX dose above and below the cut-off value was used. The ROC curve showed that 48 mg/m2 was the best cut-off value that predicted whether FN was likely to occur when pegfilgrastim was not used concurrently. The incidence of FN was 26.1% for DTX ≥48 mg/m2 and 5.1% for DTX <48 mg/m2 . Pegfilgrastim can be discontinued when the dose of DTX is reduced to <48 mg/m2 due to nonhematological toxicities.

Safety and efficacy of prophylactic pegfilgrastim on day 3 of neoadjuvant DCF chemotherapy in elderly patients with resectable esophageal cancer.

375 Background: Neoadjuvant chemotherapy with docetaxel, cisplatin plus 5-FU (Neo DCF) is one of the standard treatment for resectable esophageal cancer (EC) based on the results of the JCOG1109 study, however, a high frequency (5-30%) of febrile neutropenia (FN) has been reported with NeoDCF and the elderly (patients) pts have higher risk for FN. A single arm phase II study indicated that use of primary prophylactic pegfilgrastim (PG) on day 3 of NeoDCF might prevent FN. We compared the frequency of neutropenia and FN with or without primary prophylactic administration of PG on day 3 of NeoDCF in elderly resectable EC pts. Methods: EC pts who had received NeoDCF between 2009 and 2022, were ≥70 years old, and had adequate organ functions and PS were selected for this retrospective study. Pts were divided into two groups with Day 3 PG-containing DCF (day3 prophylactic PG: D3PG) or No PG DCF (non-prophylactic PG: NPG). Three courses of DCF (DTX [day 1]: 70 mg/m2, CDDP [day 1]: 70 mg/m2, 5-FU [continuous infusion on days 1-5]: 750 mg/m2, every 3 weeks) were planned, and prophylactic antibiotics was administered on days 5-15 in each group if possible. We retrospectively evaluated the relative dose intensity (RDI), histopathological and clinical benefit, and adverse events. Results: A total of 67 pts (D3PG, 32; NPG, 35) with a median age of 73 years were identified. The PS (0/1/2) and clinical stage (I-II/III/ IVA-B [only supraclavicular lymph node]) were 18 (56.3%)/12 (37.5%)/2 (6.2%) and 1 (3.1%)/18 (56.3%)/13 (40.6%) in the D3PG group and 20 (57.1%)/15 (42.9%)/0 and 7 (20.0%)/24 (68.6%)/4 (11.4%) in the NPG group, respectively. Six pts in the D3PG group and 3 pts in the NPG group discontinued NeoDCF because of toxicity and progression. All pts except 1 in the D3PG group underwent surgery. The RDIs (DTX/CDDP/5-FU) were 0.90/0.83/0.90 in the D3PG group and 0.83/0.83/0.83 in the NPG group. Pts who achieved a pCR (D3PG/NPG) were 7/3 (22.6%/28.6%). The common grade ≥3 adverse events (D3PG/NPG) were neutropenia (12.5%/71.4%) and FN (6.3%/20.0%). Three-year relapse-free survival rate (D3PG/NPG) was 70.8%/54.4% (hazard ratio [HR] 0.525 [95% confidence interval (CI) 0.189-1.457], p=0.216). Three-year survival rate (D3PG/NPG) was 91.8%/70.5% (HR 0.497 [95%CI 0.104-2.35], p=0.378), respectively. Conclusions: The use of primary prophylactic PG on day 3 of preoperative DCF improved the safety and maintained the RDI in the D3PG group. The efficacy was comparable between the D3PG and NPG groups despite the higher number of pts with more advanced disease in the D3PG group.

Pegfilgrastim on febrile neutropenia in pediatric and adolescent cancer patients: a systematic review and meta-analysis

ABSTRACTObjectivesThere is no meta-analysis about the effects of pegfilgrastim on the occurrence of febrile neutropenia (FN) in pediatric/adolescent cancer patients. The study explored the efficacy of prophylactic pegfilgrastim in preventing FN in children/adolescents with cancer.MethodsPubMed, Embase, and the Cochrane Library were searched for studies published before April 7, 2020. The primary outcome was the rate of FN. Effect size (ES) and odds ratio (OR) with 95% confidence intervals (CIs) were used to evaluate the outcome. The ES represented the rate of FN, and the STATA ‘metaprop’ command was used to synthesize the rate.ResultsEight studies were included, comprising 167 patients and 550 courses of treatment. There was no difference between pegfilgrastim and filgrastim for the rate of FN in children receiving chemotherapy (OR = 0.68, 95% CI: 0.20–2.23, P = 0.520). In patients receiving pegfilgrastim, the rate of FN was 25.6% (95% CI: 14.9%−36.3%), the rate of grade 4 FN was 38.3% (95% CI: 19.2%−59.5%), the rate of severe neutropenia (SN) was 40.5% (95% CI: 35.1%−46.1%), and the rate of treatment delays due to FN was 4.8% (95% CI: 0.8%−11.3%).DiscussionThe number of studies that could be included was small; therefore, a specific type of cancer or a specific treatment could be studied. Heterogeneity was high.ConclusionThere was no difference between pegfilgrastim and filgrastim for the rate of FN. The use of pegfilgrastim was still associated with rates of FN, grade 4 FN, severe neutropenia, and treatment delays due to FN in pediatric cancer patients.

Impact of relative dose intensity of trabectedin with pegfilgrastim support: a single-centre retrospective study

Relative dose intensity (RDI) has been associated with improved survival in patients with advanced solid tumours. However, there is no evidence regarding RDI in patients under long-term treatment with trabectedin for adult advanced soft tissue sarcoma (STS). Pegfilgrastim use was associated with chemotherapy dose intensity maintenance in patients with various cancers. We retrospectively evaluated the RDI in patients with STS receiving trabectedin. The patients were grouped based on whether trabectedin administration was supported by pegfilgrastim. RDI was obtained for 114 of the 140 included patients. Chemotherapy cycles that included filgrastim were excluded. Patients treated with and without pegfilgrastim had similar RDI rates (77.1% ± 17.6% vs 78.8% ± 16.4%; P = 0.485). Moreover, we found no association between patients receiving ≥4 trabectedin cycles and the use of pegfilgrastim. These results suggested that trabectedin dose delays or reductions should be considered before administering prophylactic pegfilgrastim.

Impact of the number of cryopreserved CD34+ cells in the infused blood grafts on hematologic recovery and survival in myeloma patients after autologous stem cell transplantation: Experience from the GOA study.

Prospective data on the impact of CD34+ cell loss during cryopreservation and the amount of cryopreserved CD34+ cells infused after high-dose therapy on hematologic recovery and post-transplant outcome in multiple myeloma (MM) are scarce. This post-hoc study aimed to investigate factors associating with CD34+ cell loss during cryopreservation and the effects of the infusion of a very low number (<1.0 × 106 /kg, group A), low number (1-1.9 × 106 /kg, group B), and optimal number (≥2 × 106 /kg, group C) of thawed viable CD34+ cells on hematologic recovery, progression free survival, and overall survival after autologous stem cell transplantation among 127 patients with MM. In group C, pegfilgrastim use (P=0.001), plerixafor use (P=0.039), and older age ≥ 60 years (P=0.026) were associated with less loss of CD34+ cells during cryopreservation. Better mobilization efficacy correlated with greater CD34+ cell loss in group B (P=0.013 and P=0.001) and in group C (P < 0.001 and P < 0.001). Early platelet engraftment was slowest in group A (20 d vs 12 d in group B vs 11 d in group C, P=0.003). The infused viable CD34+ cell count <1.0 × 106 /kg seemed not to have influence on PFS (P=0.322) or OS (P=0.378) in MM patients. Cryopreservation impacts significantly on the CD34+ cell loss. A very low number of graft viable CD34+ cells did not affect PFS or OS.

Pegfilgrastim in Supportive Care of Hodgkin Lymphoma.

Simple SummaryPegfilgrastim, the pegylated form of filgrastim (recombinant human GCSF) is widely adopted as supportive care for preventing neutropenia or febrile neutropenia episodes during chemotherapy. Neutropenia is directly cause of potentially severe infections and indirectly cause of treatment delivery delay. No guidelines address the pegfilgrastim role in the specific setting of Hodgkin lymphoma (HL). Since HL is a young-adult disease and shows mostly a very a favorable outcome after chemotherapy, treatment delay or dose reduction could potentially affect negatively the outcome. The aim of our review is to explore the current scientific literature on pegfilgratim use in HL, evaluating both observational than prospective trial. Moreover, analyzing the latter, we aim to define some practical suggestion about primary prophylaxis with pegfilgrastim in HL.Neutropenia and febrile neutropenia are common and potentially life-threating events associated with chemotherapy treatment in Hodgkin lymphoma (HL). Neutropenia-related infectious events could be an issue both for direct clinical consequences and for delay in treatment delivery, affecting final outcomes in a potentially highly curable disease. Pegfilgrastim is the pegylated form of filgrastim, the recombinant form of human G-CSF, capable of prevent and mitigate neutropenic effects of chemotherapy, when adopted as primary prophylaxis in several hematological malignancies. No updated version of major international guidelines provides clear indication on prophylaxis use of pegfilgrastim in HL to prevent febrile neutropenia episodes in HL. Moreover, to date, scarce and non-uniform clinical experiences evaluating pegfilgrastim as prophylaxis in HL are present in the literature. Herein, we propose a brief summary of the literature data about efficacy and safety of the use of pegfilgrastim as primary prophylaxis in HL during chemotherapy treatment.

Effect of concomitant use of G-CSF and myelosuppressive chemotherapy on bone marrow and peripheral granulocytes in a mouse model.

Granulocyte-colony stimulating factor (G-CSF) stimulates bone marrow progenitor cell proliferation and enhances neutrophil production. Exogenous G-CSF administration is indicated for chemotherapy-induced neutropenia management. However, there is a paucity of basic research examining the effects of the concomitant use of G-CSF and chemotherapy on myeloid cells in vivo. Whether concomitant G-CSF and chemotherapy adversely affect myeloid cell proliferation have not been determined. Herein, we examined the effects of the concomitant use of pegfilgrastim and 5-fluorouracil on myeloid cells and peripheral blood cells in mouse models. Balb/c mice were treated intraperitoneally with 5-fluorouracil (20μg/g b.w.) or a vehicle as a control for 5days, and pegfilgrastim was administered subcutaneously at 1μg/g b.w. on day 3. As a result, we demonstrated that the concomitant use of pegfilgrastim suppressed the 5-fluorouracil-induced decrease of granulocytic cells in both bone marrow and peripheral blood in mice. To assess the clinical efficacy of early administration of pegfilgrastim during docetaxel, cisplatin, and 5-fluorouracil therapy in patients with esophageal cancer, we retrospectively identified 42 consecutive patients treated with this regimen. The incidence of both febrile neutropenia and grade 4 neutropenia was significantly lower in patients who received pegfilgrastim than in those who did not receive it (P = 0.002 and P = 0.002, respectively). These results suggest that the concomitant use of pegfilgrastim and chemotherapy, consisting of continuous infusions of 5-fluorouracil, improved chemotherapy-induced neutropenia without detrimental effects on proliferating myeloid granulocytic cells.

Prophylactic use of pegfilgrastim enables the management of severe neutropenia without dose delays in patients with metastatic colorectal cancer treated with TAS-102 plus bevacizumab.

Combined treatment with bevacizumab and trifluridine/tipiracil (TAS-102) leads to an increased chance of survival in patients with refractory metastatic colorectal cancer (mCRC); however, this treatment is associated with an increased frequency of severe neutropenia (number of neutrophils <1,000), which should ideally be managed without dose delays. The present study provided a retrospective review of 35 patients with mCRC, and aimed to elucidate the benefits of prophylactic pegfilgrastim for the treatment of severe neutropenia. Patients received TAS-102 (35 mg/m2) orally twice daily on days 1-5 and 8-12 of each 28-day treatment cycle, along with intravenous bevacizumab (5 mg/kg) on days 1 and 15. Moreover, the patients received 3.6 mg pegfilgrastim on day 15 of each cycle. The incidence of adverse events (AEs), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were assessed. In the first and subsequent cycles, 23 and 12 patients, respectively, received pegfilgrastim. The most common AE experienced was grade 3/4 neutropenia (8 patients; 22.9%). Among these 8 patients, 6 (17.1%) and 3 (8.6%) exhibited neutropenia prior to receiving pegfilgrastim or following discontinuation of pegfilgrastim administration, respectively. Moreover, 1 individual among these 8 patients (2.9%) demonstrated grade 3 neutropenia both prior to receiving pegfilgrastim and following discontinuation of pegfilgrastim. A total of 2 patients (5.7%) exhibited grade 3 bone pain, which prevented sustainable administration of pegfilgrastim and resulted in grade 3 neutropenia. Dose delays and dose reduction of TAS-102 due to neutropenia were required in 5 (14.3%) and 2 (5.7%) patients, respectively, during the treatment period. None of the patients exhibited severe neutropenia during chemotherapy after pegfilgrastim administration, thereby preventing dose delays and dose reduction of TAS-102. The relative dose intensity was 96.8% (65.0-100.0%), and the DCR was 54.3%. The median PFS and median OS were 4.4 and 14.9 months, respectively. In conclusion, prophylactic pegfilgrastim may facilitate the management of severe neutropenia without dose delays in patients with mCRC treated with TAS-102 plus bevacizumab.

Efficacy of prophylactic pegfilgrastim on day three of preoperative DCF chemotherapy in elderly patients with resectable esophageal cancer.

305 Background: Preoperative neoadjuvant chemotherapy with cisplatin plus 5-FU (CF) is the standard treatment for resectable esophageal cancer (EC). Docetaxel plus CF (DCF) is also a promising preoperative treatment; however, a high frequency (5%-30%) of febrile neutropenia (FN) has been reported in patients (pts) receiving DCF, and elderly pts reportedly have a high risk of FN. The use of primary prophylactic pegfilgrastim (PG) on day 3 of DCF in resectable EC pts might prevent FN. We conducted a retrospective review to assess the efficacy of primary prophylactic PG administration on day 3 of preoperative DCF in elderly pts with resectable EC. Methods: EC pts who had received preoperative DCF between 2009 and 2021, were ≥70 years old, and had adequate organ functions and an adequate PS were eligible for this retrospective study. Pts were assigned to receive either PG-containing DCF (day3 prophylactic PG: D3PG) or standard DCF (non-prophylactic PG: NPG). Three courses of DCF (DTX [day 1]: 70 mg/m2, CDDP [day 1]: 70 mg/m2, 5-FU [continuous infusion on days 1-5]: 750 mg/m2, every 3 weeks) were planned, and antibiotic prophylaxis was mandatory on days 5-15 in each group. In the D3PG group, PG was administered subcutaneously on day 3. We retrospectively evaluated the relative dose intensity (RDI), histopathological efficacy, and adverse events (CTCAE ver5.0). Results: A total of 52 pts (D3PG, 17; NPG, 35) with a median age of 72 years were identified. The PS (0/1/2) and clinical stage (I/II/III/IVB [only supraclavicular lymph node]) were 10 (58.8%)/5 (29.1%)/2 (11.8%) and 0/1 (5.9%)/10 (58.8%)/6 (35.4%) in the D3PG group and 20 (57.1%)/15 (42.9%)/0 and 2 (5.7%)/5 (14.3%)/24 (68.6%)/4 (11.4%) in the NPG group, respectively. Three pts discontinued treatment because of toxicity (FN and nausea in D3PG and FN and diarrhea in NPG) and progression in each group, and all the pts underwent surgery. The RDIs (DTX/CDDP/5-FU) were 0.870/0.862/0.871 in the D3PG group and 0.833/0.829/0.830 in the NPG group. Five (29.4%) pts in the D3PG group and 10 (28.6%) in the NPG achieved a pCR. The common grade ≥3 adverse events (D3PG/NPG) were leukopenia (17.6%/51.4%), neutropenia (11.8%/71.4%) and FN (5.9%/20.0%). Conclusions: The use of primary prophylactic PG on day 3 of preoperative DCF improved the treatment safety treatment in elderly pts with resectable EC. No significant differences in treatment efficacy were seen between the D3PG and NPG groups despite the higher number of pts with a worse general condition or more advanced disease in the D3PG group than in the NPG group.

Analysis of the Safety of Pegfilgrastim Addition in Bleomycin, Etoposide, and Cisplatin Treatment Patients With Germ Cell Tumors.

It has been reported that chemotherapy drugs and granulocyte colony-stimulating factor (G-CSF) administered on the same day can aggravate neutropenia. In the present study, we investigated the safety of pegfilgrastim during bleomycin, etoposide, and cisplatin (BEP) therapy. This single-center retrospective study, including 137 cycles of BEP therapy for germ cell tumors between January 2008 and April 2021, investigated safety. Short-acting G-CSF was used for 84 cycles and pegfilgrastim was used for 53 cycles. In the pegfilgrastim group, neutrophil count at nadir was significantly higher than in the G-CSF group (median 1,650/μl and 680/μl, respectively). The incidence of grade 3–4 neutropenia was significantly higher and the duration longer in the G-CSF group. Also, there was no significant difference in the incidence of febrile neutropenia. In conclusion, concomitant use of pegfilgrastim during BEP therapy did not increase neutropenia and was effective in terms of safety.

The impact of the SARS-COV2 pandemic on the delivery of chemotherapy for gynecologic cancer at a tertiary care institution in the United States epicenter

Objectives:In New York City, the SARS-CoV2 pandemic epicenter of the United States, the surge of cases predated much of the country by several weeks, leading to changes in practice patterns that have informed decisions made by other medical institutions. As the SARS-CoV2 pandemic unfolded, many professional subspecialty organizations released practice guidelines in order to minimize transmission of COVID-19 and protect vulnerable populations. The impact of modifications to traditional gynecologic cancer treatment is not known. Here, we describe the impact of the SARS-COV2 pandemic on chemotherapy practices for gynecologic cancer during the pandemic surge.Methods:We identified patients age 18 or older at Montefiore Medical Center who had a confirmed or suspected diagnosis of gynecologic cancer and received care between March 16, 2020 and June 7, 2020; these dates reflect a series of executive orders issued by the Governor of New York allowing the State Commissioner of Health to cancel elective procedures at hospitals and ambulatory surgery centers. Clinical data were abstracted from patients’ charts. Patients with incomplete treatment records were excluded.Results:A total of 146 women who were included to whom 169 cycles of cytotoxic chemotherapy were delivered during the study period and 68 women (46.6%) received at least one cycle of chemotherapy. Nine patients screened positive for symptoms of COVID or active infection during the study period. Among patients receiving chemotherapy, 52.9% (n=36) had modifications to traditional cancer treatment as a result of state and institutional regulations. Dose reduction was the leading pandemic-related treatment modification and occurred in 69.4% of patients (n=25). Other treatment modifications included prophylactic use of pegfilgrastim (n=1), and treatment deferral or delay (n=7). Women receiving a platinum-based doublet (n=36) during the study period were more likely to sustain dose reduction in chemotherapy (25%) compared to patients undergoing other regimens (0%). A total of 111 women received at least one dose of disease-modifying therapy during the cohort period including chemotherapy, immunotherapy, anti-angiogenesis agents, hormonal therapy, PARP inhibitors, or investigational agents. Treatments were most often discontinued due to completion of adjuvant therapy (n=5), progression of disease (n=4), or toxicity (n=5). Notably 5 patients chose to defer therapy in the setting of the pandemic surge. Only one patient was identified as receiving neoadjuvant chemotherapy specifically due to COVID pandemic-related restrictions.Conclusions:The SARS-COV2 pandemic has led to modification of current standard chemotherapy delivery for gynecologic malignancies with the shared goal of protecting the most vulnerable populations from COVID infection. The impact of these modifications on cancer specific outcomes is not yet known. Future investigation will focus on identifying whether treatment modification to circumvent iatrogenic immunosuppression compromises oncologic outcomes.

Use of Pegfilgrastim in Japanese Pediatric Patients With Solid Tumors: A Retrospective Analysis.

There are no detailed analyses of regarding pegfilgrastim usage in Japanese pediatric solid tumor patients. The approved dose of pegfilgrastim in Japan is 3.6 mg. We retrospectively evaluated the incidence of dose delays and dose reductions due to neutropenia in pediatric patients with solid tumors receiving chemotherapy with pegfilgrastim between 2015 and 2018. The effects of the timing of pegfilgrastim administration were evaluated. In chemotherapies administered every 2 and 3 weeks, prolongation of chemotherapy cycles was analyzed. Fifty-nine patients received chemotherapy with prophylactic pegfilgrastim for a total 247 cycles. No significant incidence of dose delays was observed with pegfilgrastim administration during the first 1 to 3 days after chemotherapy. When 77 cycles in 2-week regimens were compared with 166 cycles in 3-week regimens, mean cycle durations were 15.19±2.06 and 21.97±2.88 days, respectively (P<0.001). A total of 77 chemotherapy cycles administered every 14 days were subdivided. The incidence of dose delays in pediatric patients receiving chemotherapy for 5 consecutive days was similar to that for 1 day and 2 consecutive days. Pegfilgrastim prophylaxis could be of use for Japanese pediatric patients with solid tumors receiving chemotherapy, including administration every 2 weeks. Its use aids in maintaining the chemotherapy schedule.