Incidence Of Febrile Neutropenia Research Articles

Impact of Malnutrition on Survival and Treatment-Related Morbidity of Cancer in Children

Background: Malnutrition is a prevalent and severe issue in pediatric oncology, affecting treatment outcomes and survival rates significantly. In developing countries, where access to comprehensive healthcare is limited, malnutrition's impact is even more profound, complicating treatment protocols and increasing morbidity and mortality rates among children with cancer. Objective: To evaluate the effects of malnutrition on survival rates and treatment-related morbidity in pediatric cancer patients, and to assess the efficacy of nutritional interventions in improving these outcomes. Methods: This retrospective study was conducted at SKMCH & RC, involving 160 newly diagnosed cancer patients aged between one and eighteen years. Patients were followed from January 2021 through March 2023. Malnutrition was assessed using WHO growth charts and defined using BMI and weight/height Z-scores. Data analysis was performed using SPSS software, version 25, focusing on survival rates, incidence of febrile neutropenia (FN), and nutritional status changes over time. Statistical significance was set at a p-value of 0.025. Results: At diagnosis, 42.5% (n=68) of the children were malnourished. After six months, 35% (n=56) remained malnourished, indicating some improvement. Malnourished children showed significantly lower survival rates, with those having a BMI Z-score ≤ -2 at six months post-diagnosis having a mortality rate HR of 4.05 (95% CI= 1.58-6.33, P = 0.009). Children experiencing a weight/height loss of >10% had an HR of 1.98 (95% CI= 1.23-6.91, P=0.04) for increased mortality. Increased episodes of FN were correlated with severe malnutrition (HR 7.32, 95% CI=1.98-10.14, P=0.0007). Conclusion: Malnutrition significantly impacts the survival rates and treatment-related morbidity in pediatric cancer patients. Early and aggressive nutritional interventions can improve survival outcomes and reduce the rate of hospitalizations due to complications like febrile neutropenia.

Efficacy and safety of venetoclax-based combination therapy for previously untreated acute myeloid leukemia: a meta-analysis

ABSTRACT Purpose: To explore the efficacy and safety of venetoclax-based combination therapy for older patients with newly diagnosed acute myeloid leukemia (AML). Methods: We performed a systematic review and meta-analysis of clinical trials comparing venetoclax plus hypomethylating agents (HMAs) or low-dose cytarabine (LDAC) with mono-HMAs or LDAC. The random or fixed effects model was applied to the studies based on heterogeneity. Dichotomous data were summarized using the risk ratio (RR) and 95% confidence interval (CI). Continuous variable data were reported as weighted mean differences (WMDs). Results: Nine studies, including a total of 1232 patients, were included in this meta-analysis. Thec complete remission (CR)/complete remission with incomplete hematological recovery (CRi) rate of the venetoclax (Ven) + azacytidine (Aza) group was significantly greater than that of the Aza monotherapy group (RR: 2.42; 95% CI: 1.85–3.15; P < 0.001). Similarly, the CR/CRi rate of the Ven + LDAC group was also significantly greater than that of the LDAC monotherapy group (RR: 2.57; 95% CI: 1.58–4.17; P = 0.00). The same results were observed for OS among these groups. However, the incidence of febrile neutropenia was greater in the Ven + Aza group than in the Ven + Decitabine (Dec) or monotherapy Aza group (RR: 0.69; 95% CI: 0.53–0.90; P = 0.006 and RR: 2.19; 95% CI: 1.58–3.03; P < 0.001, respectively). In addition, the Ven + LDAC group had significantly greater rates of constipation, diarrhea, nausea, and vomiting than the LDAC monotherapy group, with RRs and CIs of 0.61 (95% CI 0.44–0.83, P = 0.002), 1.81 (95% CI 1.22–2.67, P = 0.003), 1.39 (95% CI 1.06–1.82, P = 0.016), and 1.80 (95% CI 1.19–2.72, P = 0.005), respectively. Conclusion: Venetoclax combined with azacitidine, decitabine, or LDAC significantly improved the CR/CRi and OS of patients with previously untreated AML. However, venetoclax plus azacitidine or LDAC was more likely to lead to increased febrile neutropenia and gastrointestinal toxicity.

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.

Abstract PO2-12-12: REaCT 5G: A randomized study comparing bone pain after 5 days of filgrastim or one day of pegfilgrastim for primary febrile neutropenia prophylaxis during neo-/adjuvant chemotherapy for early breast cancer

Abstract Background: Granulocyte colony stimulating factor (G-CSF) such as filgrastim (FIL) or pegfilgrastim (PEG) significantly reduces the risk of febrile neutropenia (FN) and treatment-related hospitalization in patients with early breast cancer receiving chemotherapy. However, patients receiving G-CSF can experience clinically significant bone pain. Previous studies examining post-GCSF bone pain were mostly based on physician pain assessment and compared mixed doses (30/60/100 μg/kg) of PEG vs. FIL (5μg/kg/day or 300 μg/day) given for 7 to 14 days. Based on a randomized non-inferiority study, 5 days of FIL is considered non-inferior to 10 days of FIL to prevent FN and hospitalizations and is frequently used in patients receiving chemotherapy for breast cancer. Patient-reported bone pain after 5 days of FIL vs. single dose of PEG has never been compared in a prospective randomized study and has important implications for patient and physician treatment preferences. Methods: In this multicenter, open-label trial, patients receiving neo-/adjuvant chemotherapy for early-stage breast cancer requiring primary FN prophylaxis with G-CSF were randomized 1:1 to either 5 days of FIL (300 μg or 480μg if ≥ 90 kg) or 1 day of PEG (6 mg) with each cycle of chemotherapy. The primary endpoint was bone pain using area under the curve (AUC) of the daily pain score from days 1-5 (AUC score 0 to 40) during cycle 1. We used linear regression adjusting for stratification factors [cancer center (2 centers) and chemotherapy regimen (taxane (TAX) or anthracycline (ANTH)-based during cycle 1] and prespecified baseline covariates: age, pain, and use of pain medications pre-chemotherapy. Supportive analysis of bone pain across cycles 1 to 4 was conducted using repeated linear regression. Key secondary endpoints included incidence of FN, hospitalizations, chemotherapy delay, dose-reduction or discontinuation, and chemotherapy-related deaths. Results: From June 2021 to March 2023, 233 patients were enrolled, with 217 patients (108 FIL/109 PEG) in the intention-to-treat analysis; 16 (7.4%) patients were excluded because of incomplete follow-up. Participants were mean age 55.6 years; almost exclusively female (99.1%), on chemotherapy regimen TAX 57% vs. ANTH 43%, had mean baseline pain score 1.12, and prevalence of pain medication use pre-chemotherapy was acetaminophen 14.7%, non-steroidal anti-inflammatory drugs (NSAIDs) 6.0% and opioids 3.2%. Characteristics were balanced between arms (Table 1). After repeated measures linear regression adjusted for age, chemotherapy regimen, baseline pain, and use of pain medications pre-chemotherapy, mean AUC for bone pain at cycle 1 was 10.94 for FIL and 10.12 for PEG (mean difference 0.82; 95% CI: -1.59, 3.23; p = 0.516). There was no significant difference between arms across treatment cycles (interaction p = 0.785; mean time-averaged difference 0.28; 95% CI: -1.75, 2.32). Across cycles 1 to 4, mean peak pain over 5 days post-GCSF was 3.27 vs. 3.41 (p=0.700); frequency of bone pain during first 8 days (pain score &amp;gt; 0) was 52.5% vs. 51.3%; p=0.358, and mean frequency of severe pain (pain score ≥ 5) was 17.5% vs. 15.2%; p=0.014 for FIL vs. PEG, respectively. The incidence of FN [4.6% vs. 0%, absolute difference 4.6% (95% CI: -0.3%, 9.5%; p=0.069)] and hospitalization [FN and non-FN related: 10.2% vs. 1.8%, absolute difference of 8.4% (95% CI: 1.2%, 15.5%; p=0.021)] was higher in the FIL group. There were no significant differences in chemotherapy delay (13% vs. 11%; p=0.815), dose reduction (14.8% vs. 14.7%; p=0.999), early discontinuation (8.3% vs. 5.5%; p=0.580), or chemotherapy-related death (0.9% vs. 0%; p=0.996) in the FIL vs. PEG groups, respectively. Conclusion: There was no difference in patient-reported bone pain after 5 days of FIL or PEG, even after controlling for important clinical factors. Importantly, the study observed higher rates of FN and hospitalizations in patients receiving FIL for 5 days only. Table 1 Baseline Characteristics Citation Format: Terry Ng, Yuxin Zhang, Carol Stober, Jennifer Shamess, Natalie Mills, Stuart Nicholls, Mohammed Ibrahim, Daniel Davoudpour, Christopher Armiento, Marie-France Savard, Moira Rushton, Arif Awan, Sandeep Sehdev, John Hilton, Xinni Song, Rakesh Goel, Fiona Macdonald, Kelly Daigle, Lisa Vandermeer, Monica Taljaard, Mark Clemons. REaCT 5G: A randomized study comparing bone pain after 5 days of filgrastim or one day of pegfilgrastim for primary febrile neutropenia prophylaxis during neo-/adjuvant chemotherapy for early breast cancer [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 PO2-12-12.

Assessing Outcomes in Patients With Multiple Myeloma Postautologous Stem Cell Transplantation: Contrasting the Effects of Melphalan Dosages at 200 mg/m2 versus 140 mg/m2

BackgroundNo standard criteria for dose reduction exists for high-dose melphalan for autologous stem cell transplantation (ASCT) for multiple myeloma (MM) due to limited and conflicting evidence. ObjectiveTo evaluate efficacy and safety of standard dose (200 mg/m2 = Mel200) versus reduced dose 140 mg/m2 = Mel140) of melphalan in patients with MM undergoing ASCT. DesignA single-center retrospective review of adults with MM for their first ASCT between January 1, 2010, and November 1, 2022, who received Mel200 or Mel140 as conditioning. Primary endpoint was progression-free survival (PFS). Secondary safety and efficacy endpoints included overall survival (OS), incidence of febrile neutropenia and acute kidney injury, and time to engraftment. Subgroup analyses were performed based on patient age and renal function. ResultsA total of 322 patients were included in the study, 240 in the Mel200 group and 82 in the Mel140 group. Baseline demographics were similar except patients receiving Mel140 were on average older and had worse kidney function. PFS at 2 years was not different between groups (P = .2335). No difference existed in 2 year PFS or OS for patients < 65 years of age versus ≥ 65 years of age or for patients with CrCl 30-59 mL/min versus CrCl ≥ 60 mL/min within either Mel200 group or Mel140 group (all P > .05). No differences existed between groups across all secondary outcomes. ConclusionReduced doses melphalan showed no differences in safety or efficacy outcomes versus standard dose even when analyzed based on age and renal function. Larger randomized controlled trials need to be performed to validate these findings.

Comparison between a single dose of PEG G-CSF and multiple doses of non-PEG G-CSF: a systematic review and meta-analysis from Clinical Practice Guidelines for the use of G-CSF 2022.

Granulocyte colony-stimulating factor (G-CSF) is widely used for the primary prophylaxis of febrile neutropenia (FN). Two types of G-CSF are available in Japan, namely G-CSF chemically bound to polyethylene glycol (PEG G-CSF), which provides long-lasting effects with a single dose, and non-polyethylene glycol-bound G-CSF (non-PEG G-CSF), which must be sequentially administrated for several days. This current study investigated the utility of these treatments for the primary prophylaxis of FN through a systematic review of the literature. A detailed literature search for related studies was performed using PubMed, Ichushi-Web, and the Cochrane Library. Data were independently extracted and assessed by two reviewers. A qualitative analysis or meta-analysis was conducted to evaluate six outcomes. Through the first and second screenings, 23 and 18 articles were extracted for qualitative synthesis and meta-analysis, respectively. The incidence of FN was significantly lower in the PEG G-CSF group than in the non-PEG G-CSF group with a strong quality/certainty of evidence. The differences in other outcomes, such as overall survival, infection-related mortality, the duration of neutropenia (less than 500/μL), quality of life, and pain, were not apparent. A single dose of PEG G-CSF is strongly recommended over multiple-dose non-PEG G-CSF therapy for the primary prophylaxis of FN.

Effectiveness and safety of primary prophylaxis of G-CSF during chemotherapy for prostate cancer, Japanese clinical guideline for appropriate use of G-CSF: clinical practice guidelines for the use of G-CSF 2022.

Docetaxel (DTX) is commonly used as a primary chemotherapy, and cabazitaxel (CBZ) has shown efficacy in patients who are DTX resistant. Primary prophylactic granulocyte colony stimulating factor (G-CSF) therapy is currently used with CBZ treatment in routine clinical care in Japan. In this study, we performed a systematic review following the Minds guidelines to investigate the effectiveness and safety of primary prophylaxis with G-CSF during chemotherapy for prostate cancer and to construct G-CSF guidelines for primary prophylaxis use during chemotherapy. A comprehensive literature search of various electronic databases (PubMed, Cochrane Library, and Ichushi) was performed on January 10, 2020, to identify studies published between January 1990 and December 31, 2019 that investigate the impact of primary prophylaxis with G-CSF during CBZ administration on clinical outcomes. Ultimately, nine articles were included in the qualitative systematic review. Primary G-CSF prophylaxis during CBZ administration for metastatic castration-resistant prostate cancer was difficult to assess in terms of correlation with overall survival, mortality from infection, and patients' quality of life. These difficulties were owing to the lack of randomized controlled trials comparing patients with and without primary prophylaxis of G-CSF during CBZ administration. However, some retrospective studies have suggested that it may reduce the incidence of febrile neutropenia. G-CSF may be beneficial as primary prophylaxis during CBZ administration for metastatic castration resistant prostate cancer, and we made a "weak recommendation to perform" with an annotation of the relevant regimen.

Optimal timing of prophylactic pegylated G-CSF after chemotherapy administration for patients with cancer: a systematic review and meta-analysis from Clinical Practice Guidelines for the use of G-CSF 2022.

The timing of prophylactic pegylated granulocyte colony-stimulating factor (G-CSF) administration during cancer chemotherapy varies, with Day 2 and Days 3-5 being the most common schedules. Optimal timing remains uncertain, affecting efficacy and adverse events. This systematic review sought to evaluate the available evidence on the timing of prophylactic pegylated G-CSF administration. Based on the Minds Handbook for Clinical Practice Guideline Development, we searched the PubMed, Ichushi-Web, and Cochrane Library databases for literature published from January 1990 to December 2019. The inclusion criteria included studies among the adult population using pegfilgrastim. The search strategy focused on timing-related keywords. Two reviewers independently extracted and assessed the data. Among 300 initial search results, only four articles met the inclusion criteria. A meta-analysis for febrile neutropenia incidence suggested a potential higher incidence when pegylated G-CSF was administered on Days 3-5 than on Day 2 (odds ratio: 1.27, 95% CI 0.66-2.46, p = 0.47), with a moderate certainty of evidence. No significant difference in overall survival or mortality due to infections was observed. The trend of severe adverse events was lower on Days 3-5, without statistical significance (odds ratio: 0.72, 95% CI 0.14-3.67, p = 0.69) and with a moderate certainty of evidence. Data on pain were inconclusive. Both Day 2 and Days 3-5 were weakly recommended for pegylated G-CSF administration post-chemotherapy in patients with cancer. The limited evidence highlights the need for further research to refine recommendations.

Effectiveness and safety of primary prophylaxis of granulocyte colony-stimulating factor during dose-dense chemotherapy for urothelial cancer: Clinical Practice Guidelines for the Use of G-CSF 2022.

Granulocyte colony-stimulating factor (G-CSF) decreases the incidence, duration, and severity of febrile neutropenia (FN); however, dose reduction or withdrawal is often preferred in the management of adverse events in the treatment of urothelial cancer. It is also important to maintain therapeutic intensity in order to control disease progression and thereby relieve symptoms, such as hematuria, infection, bleeding, and pain, as well as to prolong the survival. In this clinical question, we compared treatment with primary prophylactic administration of G-CSF to maintain therapeutic intensity with conventional standard therapy without G-CSF and examined the benefits and risks as major outcomes. A detailed literature search for relevant studies was performed using PubMed, Ichu-shi Web, and Cochrane Library. Data were extracted and evaluated independently by two reviewers. A qualitative analysis of the pooled data was performed, and the risk ratios with corresponding confidence intervals were calculated and summarized in a meta-analysis. Seven studies were included in the qualitative analysis, two of which were reviewed in the meta-analysis of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) therapy, and one randomized controlled study showed a reduction in the incidence of FN. Primary prophylactic administration of G-CSF may be beneficial, as shown in a randomized controlled study of dose-dense MVAC therapy. However, there are no studies on other regimens, and we made a "weak recommendation to perform" with an annotation of the relevant regimen (dose-dense MVAC).

Effectiveness and safety of empegfilgrastim (Extimia®, BIOCAD) in patients with lymphoproliferative diseases receiving cytotoxic therapy: results of LEGERITY, a multicenter retrospective-and-prospective observational post-marketing study

Aim. To evaluate the effectiveness and safety of Extimia® BIOCAD (international non-proprietary name: empegfilgrastim) to reduce the incidence and duration of neutropenia, the incidence of febrile neutropenia (FN) and infections associated with FN in patients with lymphoproliferative diseases receiving myelosuppressive therapy.&#x0D; Materials and methods. The paper presents the results of a multicenter retrospective-and-prospective observational post-marketing study of the safety and effectiveness of Extimia® BIOCAD (international non-proprietary name: empegfilgrastim) in patients with lymphoproliferative diseases receiving cytotoxic therapy. Initially, the study was defined as retrospective-and-prospective. However, only 2 of 671 (0.3%) patients were included retrospectively. Thus, the study is based on the evaluation of prospectively collected data. The analysis describes the characteristics and treatment of 671 patients diagnosed with lymphoma who received one or more cycles of chemotherapy in the LEGERITY study. The endpoints of interest included the incidence of grade 3–4 neutropenia, FN, and grade 3–4 infectious complications, the frequency of antibiotic therapy, and the incidence of all adverse reactions in patients who received at least one dose of the study medication.&#x0D; Results. A total of 671 patients were enrolled in the study, the majority having B-cell non-Hodgkin lymphoma (428/671, 64%) and Hodgkin lymphoma (211/671, 31%). The mean age was 54 years (18–84); 35% (236/671) of patients were elderly (over 60). The number of injections of empegfilgrastim for the entire observation period was 3093 (n=671). Adverse events were reported in 57/3093 (1.8%) cases. The most common adverse events were mild to moderate ossalgia and myalgia (27/671, 4%), back pain, and arthralgia (12/671, 1.8%), which did not require drug therapy. Two patients developed serious adverse reactions – CTCAE v.5 grade 4 hypotension events. 529 (78.8%) patients received at least 4 courses of chemotherapy. FN was reported in 14 (2.6%) patients and did not require antimicrobial therapy.&#x0D; Conclusion. The final analysis results confirm the high clinical efficacy and safety of the Russian original pegylated granulocyte colony-stimulating factor empegfilgrastim (Extimia®) in patients with indolent and aggressive lymphomas. The data obtained from real-world clinical practice demonstrate a favorable safety and tolerability profile of empegfilgrastim in all age groups, including the elderly population.

Effectiveness and safety of primary prophylaxis with G-CSF for lung cancer: a systematic review and meta-analysis to develop clinical practice guidelines for the use of G-CSF 2022.

Granulocyte colony-stimulating factor (G-CSF) is commonly administered to cancer patients undergoing myelosuppressive chemotherapy, especially when incidence rate of febrile neutropenia (FN) surpasses 20%. While primary prophylaxis with G-CSF has been proven effective in preventing FN in patients with cancer, there is limited evidence regarding its efficacy in specifically, lung cancer. Our systematic review focused on the efficacy of G-CSF primary prophylaxis in lung cancer. We extracted studies on non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) using the PubMed, Ichushi Web, and Cochrane Library databases. Two reviewers assessed the extracted studies for each type of lung cancer and conducted quantitative and meta-analyses of preplanned outcomes, including overall survival, FN incidence, infection-related mortality, quality of life, and musculoskeletal pain. A limited number of studies were extracted: two on NSCLC and six on SCLC. A meta-analysis was not conducted owing to insufficient data on NSCLC. Two case-control studies explored the efficacy of primary prophylaxis with G-CSF in patients with NSCLC (on docetaxel and ramucirumab therapy) and indicated a lower FN frequency with G-CSF. For SCLC, meta-analysis of five studies showed no significant reduction in FN incidence, with an odds ratio of 0.38 (95% confidence interval 0.03-5.56, P = 0.48). Outcomes other than FN incidence could not be evaluated due to low data availability. Limited data are available on G-CSF prophylaxis in lung cancer. Primary prophylaxis with G-CSF may be weakly recommended in Japanese patients with NSCLC undergoing docetaxel and ramucirumab combination therapy.

Predictive Model for Occurrence of Febrile Neutropenia after Chemotherapy in Patients with Diffuse Large B-Cell Lymphoma: A Multicenter, Retrospective, Observational Study.

Febrile neutropenia (FN) is a major concern in patients undergoing chemotherapy for diffuse large B-cell lymphoma (DLBCL); however, the overall risk of FN is difficult to assess. This study aimed to develop a model for predicting the occurrence of FN in patients with DLBCL. In this multicenter, retrospective, observational analysis, a multivariate logistic regression model was used to analyze the association between FN incidence and pretreatment clinical factors. We included adult inpatients and outpatients (aged ≥ 18 years) diagnosed with DLBCL who were treated with chemotherapy. The study examined 246 patients. Considering FN occurring during the first cycle of chemotherapy as the primary outcome, a predictive model with a total score of 5 points was constructed as follows: 1 point each for a positive hepatitis panel, extranodal involvement, and a high level of soluble interleukin-2 receptor and 2 points for lymphopenia. The area under the receiver operating characteristic curve of this model was 0.844 (95% confidence interval: 0.777-0.911). Our predictive model can assess the risk of FN before patients with DLBCL start chemotherapy, leading to better outcomes.

Phase II study of the safety and efficacy of discontinuing pegfilgrastim for pancreatic adenocarcinoma treated with FOLFIRINOX.

663 Background: The original FOLFIRINOX regimen (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) for pancreatic ductal adenocarcinoma (PDAC) is associated with a high risk of febrile neutropenia (FN), and pegfilgrastim has been used to reduce the risk. However, it remains unclear how long pegfilgrastim needs to continue. This study evaluated the safety and efficacy of FOLFIRINOX after discontinuing pegfilgrastim in PDAC patients. Methods: This prospective phase II trial included patients with PDAC who received the first three courses of FOLFIRINOX, with primary pegfilgrastim prophylaxis for FN, and did not experience FN. The patients continued on FOLFIRINOX without pegfilgrastim from the fourth course. The primary endpoint was development of FN. The secondary endpoints included relative dose intensity (RDI), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The threshold and expected development of FN were 20% and 7%, respectively, at a one-sided significance level of 0.10 and statistical power of 80%. Based on this hypothesis, we calculated the number of patients needed to be 33. Results: In total, 34 patients (20 male, median age 66 years) were enrolled from August 2017 to September 2021. Twenty-three patients were unresectable, and 11 were borderline resectable. FN developed in one patient. Grade 4 neutropenia was observed in six patients, grade 3 neutropenia in 10 (29.4%), anemia in four (11.8%), diarrhea in two (5.9%), and malaise, lung infection, peripheral sensory neuropathy, colitis, and biliary tract infection in one (2.9%) each. Twenty-two patients required dose reduction, mainly because of neutropenia. Mean RDIs at the sixth course of oxaliplatin, irinotecan, leucovorin, acute infusion of fluorouracil, and continuous infusion of fluorouracil were 77.0%, 88.2%, 81.8%, 84.4%, and 87.6%, respectively. ORR, median PFS, and median OS were 44.1%, 15.8 months, and 25.8 months, respectively. Conclusions: FOLFIRINOX can be continued safely with a low incidence of FN after discontinuing pegfilgrastim in PDAC patients who did not experience FN during the first three courses of FOLFIRINOX, if the drug dose is reduced appropriately for neutropenia from the fourth course. Clinical trial information: UMIN000028055 .

A retrospective analysis of the efficacy and safety of capecitabine plus oxaliplatin (CapeOX) and docetaxel plus S-1 (DS) as adjuvant chemotherapy for pathological stage III (p stage III) gastric cancer (GC).

342 Background: Adjuvant chemotherapy following surgical resection is the standard treatment for patients with p stage III GC in Japan. Although CapeOX and DS are available for adjuvant chemotherapy for stage III GC, there is limited data on which treatment is more effective. We aim to compare the efficacy and safety of CapeOX and DS as adjuvant chemotherapy in patients with p stage III GC. Methods: We extracted data of patients with p stage III GC who received either CapeOX (capecitabine on days 1–14 plus oxaliplatin on day1 for 8 cycles [q 3week]) or DS (S-1 on days 1–14 at 1st cycle [q 3 week], docetaxel on day 1 plus S-1 on days 1–14 during 2–7 cycles [q 3 week], and S-1 on days 1–28 up to 1 year [q 6 week]) as adjuvant chemotherapy after surgical resection at our institution from February 2016 to May 2022. Three-year relapse-free survival (RFS) and adverse events (AEs) were assessed. Cox proportional hazard model was used in multivariable analysis to assess the effect of independent variables on RFS. Results: A total of 74 patients were included in this study (CapeOX 31/ DS 43). Patient characteristics (CapeOX/DS) were as follows: median age, 60/64 years; male, 77/65 %; ECOG-PS 0/1, 45%/44%, 55%/56 %; p stage IIIA/IIIB/IIIC, 10%/30%, 48%/51 %, 42%/19 %. The 3-year RFS was 37% in the (hazard ratio [HR] = 0.81, P=0.48). For p stage IIIA, IIIB, and IIIC, the 3-year RFS in the CapeOX group and the DS group was 67% vs. 75% (HR = 0.56, P =0.52), 43% vs. 42% (HR = 1.11, P =0.81), and 23% vs. 0% (HR = 1.59, P =0.39), respectively. Multivariable analysis adjusted for p stage showed no significant differences in RFS between the CapeOX group and the DS group (HR=1.06, P=0.85). Compared to DS, CapeOX was associated with lower incidences of febrile neutropenia (0% vs 7%) and alopecia (6% vs 74%), and a higher incidence of peripheral neuropathy (80% vs 23%). Conclusions: This analysis indicates that CapeOX and DS have comparable efficacy as adjuvant chemotherapy for p stage III GC in terms of RFS, albeit with different profiles of AEs.

Pharmacoeconomic analysis of using empegfilgrastim for the treatment of early and locally advanced HER2+ breast cancer in the Russian Federation

Objective: to assess budget impact of using empegfilgrastim for the prevention of febrile neutropenia in patients with early and locally advanced human epidermal growth factor receptor 2 positive (HER2+) breast cancer who receive neoadjuvant “docetaxel / carboplatin / trastuzumab + pertuzumab” regimen, considering possible subsequent adjuvant therapy with trastuzumab emtansine or trastuzumab within the Russian healthcare system.Material and methods. We searched and analyzed published clinical, epidemiological and pharmacoeconomic studies as well as regulatory and legal documents. A decision tree model was constructed to reflect the probabilities of switching to different adjuvant therapy regimens depending on the achievement of pathomorphological complete response in patients with early and locally advanced HER2+ breast cancer. The budget impact analysis was carried out comparing two primary prophylactic options, empegfilgrastim and filgrastim.Results. Despite the higher costs of prevention with empegfilgrastim compared to filgrastim (249 vs. 134 thousand rubles), due to the higher rate of achieving a pathomorphological complete response and, accordingly, fewer cases requiring adjuvant therapy with the more expensive trastuzumab emtanzine, savings of 916 thousand rubles per 1 patient per 1 year of therapy are possible. In general, prophylaxis in the target population diagnosed with early and locally advanced HER2+ breast cancer using empegfilgrastim will result in a cost reduction of 9.4 billion rubles per 1 year compared to filgrastim.Conclusion. Empegfilgrastim prophylaxis, despite its higher annual cost, is an efficient option within the Russian healthcare system. In addition to reducing the incidence of febrile neutropenia, the frequency and dose of chemotherapy are preserved, resulting in increased efficacy of the primary therapy.

Analysis of Risk Factors for Febrile Neutropenia in Patients with Small-Cell Lung Cancer Receiving Carboplatin Plus Etoposide Therapy

Introduction: Febrile neutropenia (FN) is an oncologic emergency requiring immediate empiric antibiotic therapy. Although carboplatin plus etoposide combination chemotherapy is associated with a relatively high frequency of FN, the risk factors are unclear. Hence, this retrospective study aimed to identify predictive markers of carboplatin/etoposide-induced FN. Methods: We conducted a retrospective cohort analysis of patients with previously untreated small-cell lung cancer (SCLC) who received combination chemotherapy with carboplatin (area under the concentration curve: 5 mg/mL·min, day 1) and etoposide (80 or 100 mg/m2, days 1–3) between July 2007 and June 2022. FN was assessed during the 21 days after initiation of carboplatin and etoposide therapy according to the Japanese Society of Medical Oncology’s definition. Fisher’s exact test for categorical variables and Mann-Whitney U test for continuous variables were used to compare the two groups. Statistical significance was set at p values p values Results: Among the 176 eligible patients, the incidence of FN during the first cycle of chemotherapy was 25.0% (44/176). Multivariate analysis revealed that co-administration of proton pump inhibitors (PPIs) or potassium-competitive acid blockers (PCABs) and body mass index (BMI) were significantly associated with FN (p = 0.0035 and 0.0011, respectively). Patients with both co-administration of PPIs or PCABs and a BMI ≤22.509 kg/m2 presented with significantly higher frequencies of FN compared with the other patients (13/24 [54.2%] vs. 31/152 [20.4%] patients; odds ratio: 4.56, 95% confidence interval: 1.70–12.48; p = 0.00147). Conclusion: Patients who received carboplatin plus etoposide for SCLC with co-administration of PPIs or PCABs and a BMI ≤22.509 kg/m2 more frequently present with FN than those without the two factors.

Febrile neutropenia incidence and the variable toxicity profile between brand and generic docetaxel in the adjuvant treatment of breast cancer with docetaxel and cyclophosphamide regimen.

To assess the incidence of febrile neutropenia without primary granulocyte colony-stimulating factor prophylaxis in patients undergoing chemotherapy with adjuvant docetaxel and cyclophosphamide, and to evaluate the toxicity profile of brand-name docetaxel (Taxotere ® ) and the generic formulation. This retrospective study was conducted using data obtained from electronic medical records of patients treated at a Brazilian cancer center. Patients with breast cancer who underwent adjuvant treatment between January 2016 and June 2019 were selected. Data were analyzed using chi-square and Fisher correlation of variables, and multivariate analyses were adjusted for propensity score. A total of 231 patients with a mean age of 55.9 years at the time of treatment were included in the study. The majority (93.9%) had luminal histology, 84.8% were at clinical stage I, and 98.2% had a good performance status. The overall incidence of febrile neutropenia in the study population was 13.4% (31 cases). The use of brand-name docetaxel (Taxotere ® ) was the only factor associated with febrile neutropenia occurrence (OR= 3.55, 95%CI= 1.58-7.94, p=0.002). In patients with breast cancer who require treatment with adjuvant docetaxel and cyclophosphamide regimen, the toxicity profile differs between brand-name and generic docetaxel. Regardless of the formulation used, the incidence of febrile neutropenia was less than 20%, which may allow for the omission of primary prophylactic granulocyte colony-stimulating factor use in this setting.

Efbemalenograstim alfa, an Fc fusion protein, long-acting granulocyte-colony stimulating factor for reducing the risk of febrile neutropenia following chemotherapy: results of a phase III trial

PurposeEvaluate the safety and efficacy of efbemalenograstim alfa for reducing the risk of febrile neutropenia in breast cancer patients undergoing myelosuppressive chemotherapy.MethodsA phase III, randomized, double-blind, placebo-controlled study was conducted. A total of 122 subjects received up to 4 cycles of TA chemotherapy (75 mg/m2 docetaxel + 60 mg/m2 doxorubicin). Patients were randomized in a 2:1 ratio to subcutaneously inject a single 20 mg of efbemalenograstim alfa or placebo on day 2 of cycle 1, and all subjects received efbemalenograstim alfa on day 2 of cycles 2, 3, and 4. Duration of severe (grade 4) neutropenia (DSN), depth of neutrophil nadir, incidence of febrile neutropenia (FN), time to neutrophil recovery, and safety information were recorded.ResultsFor the primary endpoint, the mean DSN in cycle 1 was 1.3 days and 3.9 days for efbemalenograstim alfa and placebo respectively (95% CI, 2.3, 3.4). As the lower bound of the 95% CI was > 0, superiority of efbemalenograstim alfa over placebo can be declared. In addition, the incidence of FN in Cycle 1 was lower in efbemalenograstim alfa group than in placebo group (4.8% vs. 25.6%; p = 0.0016). Patients in the efbemalenograstim alfa group required less intravenous antibiotics (3.6% vs. 17.9%; p = 0.0119). Most adverse events were consistent with those expected for breast cancer patient receiving TA chemotherapy.ConclusionEfbemalenograstim alfa is effective and safe for significantly decreasing the duration of severe neutropenia and the incidence of febrile neutropenia in breast cancer patients who are receiving TA chemotherapy.Trial registration.NCT02872103, August 19, 2016.

The frequency of regimens associated with high risk of febrile neutropenia and the incidence of dose-limiting neutropenia among patients receiving cytotoxic therapy for malignancies: the FLAME study results

Aim. To assess the proportion and profile of patients at high risk of febrile neutropenia (FN) receiving cytotoxic chemotherapy (CT), as well as the incidence of FN and dose-limiting neutropenia after one cycle of CT.&#x0D; Materials and methods. The paper presents the results of the FLAME study, the first Russian observational study in patients with solid tumors who received only cytotoxic CT or a combination with targeted, immuno-oncological drugs. By random sampling, the study retrospectively included 500 patients with a median age of 59 years (18–83 years) from 25 medical institutions in the Russian Federation.&#x0D; Results. CT regimens with a high (20%) risk of FN were received by 25.2% (126/500) of patients; 53% (265/500) of patients had intermediate risk, and half of them (132/265 [49.8%]) had at least one additional risk FN factor following international NCCN guidelines. Thus, a high risk of FN, according to the therapy and the assessment of individual prognostic adverse factors, was noted in 51.6% (258/500) of patients. 36.8% (95/258) of patients with high risk for FN received primary prophylaxis with granulocyte colony-stimulating factors.&#x0D; Conclusion. The study showed a significant proportion of patients with a high risk of FN, and most of them do not receive primary prophylaxis of FN.

Pegfilgrastim for the management of neutropenia during neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil in esophageal cancer patients.

Neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy is a new standard for locally advanced esophageal squamous cell carcinoma. The optimal timing of pegfilgrastim with the DCF regimen to prevent febrile neutropenia (FN) remains controversial. The effectiveness of concomitant pegfilgrastim administration with continuous 5-fluorouracil (5-FU) infusion in the DCF regimen was therefore assessed. All patients who received neoadjuvant DCF for esophageal cancer were retrospectively assessed. Patients who had been scheduled to receive pegfilgrastim on days 3-5 (early group) or days 7-9 (regular group) of the DCF regimen were included. Uni- and multivariate analyses were used to assess risk factors for FN. Eighty-eight patients were included in the analysis. The 26 patients in the early group received pegfilgrastim as scheduled. In the 62 patients of the regular group, 51 received pegfilgrastim at a median of 7days after starting DCF chemotherapy. However, 11 patients in the regular group could not receive pegfilgrastim. Twenty-two patients of the regular group and 2 patients of the early group developed FN after the first session of DCF. Early administration of pegfilgrastim and grade 4 neutropenia were significantly associated with onset of FN, with multivariate analysis identifying early administration of pegfilgrastim as an independent preventive factor and grade 4 neutropenia as a risk factor, after adjusting for sex and age. Early pegfilgrastim administration is a safe approach that reduces the incidence of FN in DCF therapy. Using pegfilgrastim with continuous 5-FU infusion in the DCF regimen represents a reasonable option to prevent FN.