Management Of Chemotherapy-induced Neutropenia Research Articles

Impact of 10% Dose Reductions and Duration of Treatment Delays in the Management of Chemotherapy-Induced Neutropenia in Dogs Treated With Common Chemotherapy Protocols: A Single-Centre Experience.

Neutropenia is a common chemotherapy-associated adverse event (AE) in dogs and a significant cause of decreased relative dose intensity. Dose reductions (DRs) and treatment delays (TDs) are frequently applied to decrease the risk of further neutropenic events (NEs) and AEs, but there is no standardised approach. The two main objectives of this retrospective study were to determine: (1) the failure rate of a 10% DR to prevent a subsequent inadequate absolute neutrophil count (ANC), defined as a nadir ANC <0.75 × 109/L or pretreatment ANC <1.5 × 109/L; and (2) if the duration of TDs due to pretreatment neutropenia affects the occurrence of subsequent NEs. A total of 1056 chemotherapy treatments were recorded for 128 dogs that developed at least one NE. In 75 of 124 (60.5%, 95% CI: 51.2%-69%) evaluable NEs, a nadir ANC of ≥0.75 × 109/L and pretreatment ANC of ≥1.5 × 109/L were achieved after a single 10% chemotherapy DR, while a 10% DR failed to prevent a subsequent inadequate ANC in the remaining 49/124 (39.5%, 95% CI: 30.1%-48.3%). The only variable associated with failure was the drug prescribed. DR failure occurred in 22/39 (56.4%, 95% CI: 40.9%-70.6%) lomustine DRs, 14/27 (51.9%, 95% CI: 33.9%-69.2%) cyclophosphamide DRs, but only 2/22 (9.1%, 95% CI: 2.5%-27.8%) doxorubicin DRs and 2/24 (8.3%, 95% CI: 2.3%-25.8%) vincristine DRs. Seventy-three evaluable TDs (mean: 5 days, SD ± 2.2 days) were prescribed. There was no association between TD duration and subsequent NEs (p = 0.11).

Abstract P5-16-14: A randomized, multicenter phase III study of once-per-cycle administration of efbemalenograstim alfa (F-627), a novel long-acting dimeric rhG-CSF, for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer

Abstract Background: Neutropenia is common in patients receiving myelotoxic chemotherapy. F-627( efbemalenograstim alfa ), is a novel long acting dimeric granulocyte colony-stimulating factor (G-CSF) that contains two human G-CSF fused to a human immunoglobulin G2 (hIgG2) -Fc fragment with a peptide linker. This study was to evaluate the efficacy and safety of F-627 for reducing chemotherapy-induced neutropenia as compared with filgrastim (GRAN®). Methods: This was a multicenter, randomized, open-label, and active-controlled non-inferiority study. Thirteen centers enrolled 239 patients who received chemotherapy with epirubicin (100mg/m2) and cyclophosphamide (600 mg/m2) (EC therapy) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive on day 3 either a single 20 mg subcutaneous (s.c.) injection of F-627 per cycle or daily s.c injections of filgrastim 5 μg/kg/day. The primary endpoint was the duration of grade 3 (ANC &amp;lt;1× 109/L) or 4 (ANC&amp;lt;0.5× 109/L) neutropenia in cycle 1. The safety profile was evaluated. Results: The mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.67 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimator of the median difference between groups (F-627 − Filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of one-sided 97.5% CI was 0 days, which was within the 1-day prespecified non-inferiority margin. Results for all efficacy end points in cycles 2−4 was consistent with the results from cycle 1, however a trend towards a lower incidence and a shorter duration of grade 3 or 4 neutropenia and grade 4 neutropenia was observed with F-627 compared with filgrastim. The nadir in the F-627 group was higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as multiple daily doses of filgrastim. The most frequently reported adverse events considered to be related to the study drug were bone pain and back pain. No deaths occurred during the study. 5.0% of F-627 patients and 6.7% of filgrastim patients reported serious adverse events (SAEs). The incidence of SAEs was low in both groups and no SAEs were related to study drugs, and were resolved during the study. Conclusions: A single fixed dose of 20 mg of F-627 was as safe and effective as multiple daily doses of filgrastim 5μg/kg/day in reducing chemotherapy-induced neutropenia and its complications in patients who received four cycles of EC therapy. F-627 provides the Chinese oncologists an alternative for simplifying the management of chemotherapy-induced neutropenia. The study was approved by the National Medical Products Administration of China (registration number: 2017L04033), and was registered on www.chinadrugtrials.org.cn (registration number: CTR20170705) and ClinicalTrials.gov (registration number: NCT04174599). Citation Format: William Daley, Zhimin Shao, Qingyuan Zhang, Hongshen Li, Changshen Ye, Shufang Wang, Langxi Zhang, Gaochong Zhang, Jianmin Chen. A randomized, multicenter phase III study of once-per-cycle administration of efbemalenograstim alfa (F-627), a novel long-acting dimeric rhG-CSF, for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-16-14.

Student nurses' knowledge about the management of chemotherapy-induced neutropenia: Multi-national survey

BackgroundChemotherapy-induced neutropenia is a serious global health concern. It is essential that student nurses who are the future of healthcare are equipped with the right knowledge to care for the unique needs of patients with neutropenia. ObjectiveThe study assesses student nurses' knowledge of neutropenia management and examines the difference in their knowledge with regard to their demographics. DesignA descriptive cross-sectional survey design was used. SettingsParticipants for this survey were recruited from four nursing schools from three countries: Jordan, Oman, and Saudi Arabia. ParticipantsThe study sample comprised 230 student nurses representing all three countries. MethodsOnline data collection was implemented. A message including the link to the study questionnaire was sent to students through their university portal. Demographic data and the neutropenia knowledge questionnaire were collected. ResultsThe student nurses showed poor knowledge of neutropenia and its management (mean = 10.1 out of 30). The bridging students (M = 12.6, SD = 9.8) had significantly higher mean total knowledge scores than the regular students (M = 9.8, SD = 5.5) (t = 2.9, df = 38.9, p = 0.006). However, students who had received previous education about neutropenia management (M = 11.6, SD = 5.0) had significantly higher mean knowledge scores than those who had not (M = 9.5, SD = 5.6) (t = −2.73, df = 134.8, p = 0.007). ConclusionsThe study findings underscore the overarching necessity to improve students' knowledge of neutropenia and its management. However, addressing this concern is multifaceted and requires deliberate effort from various agencies. Developing innovative strategies to increase the coverage of oncology nursing in the curriculum, improving faculty expertise, enhancing staff nurses' knowledge and skills, provision of funding, and adoption of oncology-related competencies in the nursing program need to be explored as key solutions.

Management of chemotherapy-induced neutropenia in patients with cancer: 2019 guidelines of the Italian Medical Oncology Association (AIOM).

Neutropenia is the most frequent side effect of commercially available myelosuppressive drugs and its most significant complication is febrile neutropenia. It is associated with increased hospital admissions and higher probability of death. Prophylaxis with the administration of granulocyte colony-stimulating factor can prevent neutropenia caused by anticancer drugs. The correct administration of these drugs and the management of febrile neutropenia are extremely important in the treatment of patients with cancer.

Recent advances in the management of chemotherapy-induced neutropenia: biosimilar granulocyte colony-stimulating factor use in Italy.

During the National Congress of the Italian Association of Medical Oncology, which was held in Rome, Italy, October 2019, experts met to discuss advantages of febrile neutropenia prevention based on biosimilar G-CSF. This issue is of paramount importance in oncology as recent biological products may be of great benefit, provided that costs are sustainable.

Abstract P2-14-12: Eflapegrastim, a novel long-acting granulocyte-colony stimulating factor: Integrated safety results in patients with early-stage breast cancer treated with TC chemotherapy

Abstract Background: Eflapegrastim (E) represents the first myeloid growth factor innovation in more than 15 years. A novel, long-acting recombinant human granulocyte-colony stimulating factor (rhG-CSF), E consists of a rhG-CSF analog conjugated to a human IgG4 Fc fragment via a polyethylene glycol linker. Preclinical and Phase I and II pharmacodynamic and pharmacokinetic data showed increased potency for E versus pegfilgrastim (P). Two independent randomized Phase III trials comparing fixed dose E and P (E 3.6 mg G-CSF and P 6.0 mg G-CSF) for the management of chemotherapy-induced neutropenia (CIN) have recently been completed. Both trials met the primary endpoint of non-inferiority for E vs P in Cycle 1 duration of severe neutropenia (P&amp;lt;.001). Here we provide an integrated summary of the safety of E administered at a fixed dose in a pre-filled syringe. Patients and Methods: Patients with early-stage breast cancer (ESBC) who were candidates for adjuvant or neoadjuvant chemotherapy were randomized 1:1 in two open-label Phase III trials to E 13.2 mg (3.6 mg G-CSF) or standard P (6 mg G-CSF) administered on Day 2 following TC (docetaxel/cyclophosphamide) chemotherapy on Day 1 of each of 4 cycles. Blood for CBC and serum chemistry was collected in every cycle. Safety assessments began with the first dose of TC and continued for one year after the last dose of study drug. AEs and laboratory values were graded according to NCI CTCAE version 4.03. Immunogenicity was assessed from blood samples collected on Day 1 of each cycle, at the end-of-treatment visit, and at 6- and 12-month follow-up visits. Results: A total of 660 patients who received at least one dose of eflapegrastim (n=334) or pegfilgrastim (n=326) were included in this integrated safety analysis. The two treatment groups were well balanced for demographics and baseline disease characteristics. The mean age was 59y, ~40% were aged &amp;gt;65y, ~54% weighed &amp;gt;75kg, and ~80% were treated in the adjuvant setting. Median relative dose intensity for T and C was &amp;gt;99% for both groups. A similar percentage of patients in both treatment groups discontinued treatment due to AEs (4% E vs 6% P), with 2% in each group discontinuing due to AEs related to E or P. Serious AEs were similar in both groups (15% each). Incidence of AEs irrespective of causality were also similar between groups (74% E vs. 72% P). No notable differences between groups were observed in the types of study-drug-related AEs. The majority of study-drug-related AEs occurred with an incidence ≤10% for both E and P. As expected with myeloid growth factors, study-drug-related AEs occurring in &amp;gt;10% in either group were bone pain (E vs P: 33% vs 34%), arthralgia (15% vs 10%), back pain (14% vs 9%), myalgia (14% vs 9%), and headache (11% vs 8%). Incidence of febrile neutropenia and neutropenic complications were similar and less than 5% in each treatment group. No leukocytosis, splenic rupture, or anaphylaxis was reported in any patient receiving E or P. The overall incidence of immunogenicity was similar in both groups and there was no demonstrable impact on clinical safety or efficacy. Conclusions: Two large, randomized Phase III trials (Total n=660) of E vs P administered once-per-cycle showed E at a lower G-CSF dose to be safe and effective for the prophylaxis of CIN in patients with ESBC receiving TC chemotherapy. E is a novel long-acting rhG-CSF with increased potency and similar toxicity to P and may provide an attractive alternative for growth factor support of patients at high risk for CIN-related complications. Citation Format: Lee S Schwartzberg, Gajanan Bhat, Julio Peguero, Richy Agajanian, Jayaram Bharadwaj, Alvaro Restrepo, Osama Hlalah, Inderjit Mehmi, Shanta Chawla, Francois Lebel, Patrick W Cobb. Eflapegrastim, a novel long-acting granulocyte-colony stimulating factor: Integrated safety results in patients with early-stage breast cancer treated with TC chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-14-12.

LA-EP2006: A Pegfilgrastim Biosimilar.

LA-EP2006 (Ziextenzo®) is the fifth biosimilar of pegfilgrastim, a pegylated recombinant granulocyte colony-stimulating factor, to be approved in the EU. It is approved for use in adults treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia and myelodysplastic syndromes) to reduce the duration of neutropenia and the incidence of febrile neutropenia. LA-EP2006 matched reference pegfilgrastim in terms of physicochemical characteristics and functional properties, and the pharmacodynamic and pharmacokinetic similarity of the medicines has been shown in healthy volunteers. LA-EP2006 demonstrated clinical efficacy equivalent to that of EU-sourced reference pegfilgrastim in adult women with breast cancer receiving chemotherapy. The tolerability and safety profile of and the incidence of anti-drug antibodies with LA-EP2006 were similar to those of EU-sourced reference pegfilgrastim in this patient population. The role of reference pegfilgrastim in the management of chemotherapy-induced neutropenia is well established and LA-EP2006 provides an effective biosimilar alternative for patients requiring pegfilgrastim therapy.

Pegfilgrastim-jmdb/MYL-1401H: A Pegfilgrastim Biosimilar

Pegfilgrastim-jmdb/MYL-1401H (FULPHILA™) [hereafter referred to as pegfilgrastim-jmdb] is a biosimilar of the reference pegylated recombinant granulocyte colony-stimulating factor pegfilgrastim. It is approved for use in patients receiving chemotherapy for malignancy to decrease the incidence of infection, as manifested by febrile neutropenia, in the USA and to reduce the duration of neutropenia and the incidence of febrile neutropenia in the EU. Pegfilgrastim-jmdb has similar physicochemical characteristics and functional properties to those of US- and EU-sourced reference pegfilgrastim, and the pharmacodynamic and pharmacokinetic similarity of the agents has also been demonstrated in healthy volunteers. Pegfilgrastim-jmdb demonstrated clinical efficacy equivalent to that of EU-sourced reference pegfilgrastim in patients with newly diagnosed Stage II/III breast cancer receiving neoadjuvant or adjuvant chemotherapy and was generally well tolerated in this patient population. The overall safety profile and immunogenic potential of the two agents was similar. The role of reference pegfilgrastim in the management of chemotherapy-induced neutropenia is well established and pegfilgrastim-jmdb provides an effective biosimilar alternative for patients requiring pegfilgrastim therapy.

Outcomes of chemotherapy-induced (febrile) neutropenia prophylaxis with biosimilar filgrastim (Zarzio®) initiated "same-day" (< 24h), "per-guidelines" (24-72h), and "late" (> 72h): findings from the MONITOR-GCSF study.

Granulocyte colony-stimulating factors (G-CSFs) are indicated for prophylaxis or management of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN). Guidelines recommend G-CSF 24-72h following chemotherapy; however, some evidence suggests that G-CSF initiated < 24h may benefit some patients. MONITOR-GCSF was a prospective, observational, multicenter, pan-European study of 1447 chemotherapy-treated patients receiving daily biosimilar (standard) filgrastim (Zarzio®/Zarxio®, filgrastim-sndz, Hexal AG, Sandoz Inc.). In this analysis, cycles were classified as same-day, per-guidelines, or late if G-CSF support was initiated < 24h, 24-72h, and > 72h after chemotherapy. Outcomes included occurrence of CIN of any grade (CIN1/4), grade 3 or 4 (CIN3/4), grade 4 (CIN4), or FN: CIN/FN-related hospitalization or CIN/FN-related chemotherapy disturbance. A total of 5930 chemotherapy cycles from 1423 evaluable patients from MONITOR-GCSF had data for day of G-CSF initiation: 795cycles (13.4%) classified as same-day, 3320 (56.0%) as per-guidelines, and 1815 (30.6%) as late. Groups did not differ as to CIN1/4 and FN episodes, or CIN/FN-related hospitalizations or chemotherapy disturbances. Patients in the same-day and per-guidelines groups had statistically similar odds of not experiencing any outcomes of interest in any given cycle. Patients in the late group had worse odds of experiencing CIN1/4, CIN3/4, and CIN4 episodes in any given cycle. Proportions of patients reporting clinical events of interest were generally similar. This real-world evidence indicates that CIN/FN prophylaxis initiated with biosimilar filgrastim within 24-72h post-chemotherapy is effective and safe. Filgrastim administration on the day of chemotherapy may be appropriate in some patients.

Abstract OT1-01-11: Randomized phase 3 study of a novel, long-acting G-CSF (eflapegrastim) versus pegfilgrastim in the management of chemotherapy-induced neutropenia in early-stage breast cancer patients receiving docetaxel and cyclophosphamide (TC) (ADVANCE study)

Abstract Background: Eflapegrastim is a distinct biologic that uses an innovative, proprietary long-acting protein/peptide discovery technology (LAPSCOVERY™). Eflapegrastim consists of a novel, modified recombinant human G-CSF conjugated to the Fc fragment of IgG4 via a polyethylene glycol linker to produce a new, longer-acting G-CSF with a potentially unique distribution to areas rich in Fc receptors including its site of action in the bone marrow. A successful dose-finding Phase 2 trial including a pegfilgrastim control arm established the dose for a Phase 3 non-inferiority trial. Trial Design: This is a randomized, open-label, active-controlled, multinational, multicenter, Phase 3 study comparing the efficacy and safety of eflapegrastim to pegfilgrastim. Patients (n=580) will be randomized in a 1:1 ratio to receive either eflapegrastim (equivalent to 3.6 mg G-CSF) or pegfilgrastim (equivalent to 6.0 mg G-CSF) once per chemotherapy cycle (up to 4 cycles), approximately 24 hours after chemotherapy. The primary endpoint is to compare the efficacy of a single dose of eflapegrastim with pegfilgrastim in patients with ESBC receiving TC, as measured by the Duration of Severe Neutropenia (DSN) in Cycle 1. Key secondary objectives include Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1; Depth of ANC Nadir in Cycle 1; incidence of Febrile Neutropenia. Safety and pharmacokinetics will also be assessed. Eligibility Criteria: This study is enrolling histologically confirmed ESBC patients who are: eligible to receive adjuvant or neoadjuvant TC chemotherapy; at least 18 years of age, with adequate hematologic, renal and hepatic function. Patients will be excluded if they have: active concurrent malignancy or life-threatening disease; a known sensitivity or previous reaction to E. coli derived products or any of the products to be administered during study participation; concurrent adjuvant cancer therapy; locally recurrent/metastatic or contralateral breast cancer; previous exposure to filgrastim, pegfilgrastim, or other G-CSF products in clinical development prior to the administration of study drug; bone marrow or hematopoietic stem cell transplant or radiation therapy prior to enrollment, or are pregnant or breast-feeding. Statistical Methods: The goal of this study is to demonstrate non-inferiority. For the Primary Efficacy Analysis, the mean DSN in Cycle 1 will be compared between the eflapegrastim and pegfilgrastim treatment arms. A 2-sided 95% confidence interval (CI) of the difference between the mean DSN of the eflapegrastim arm and the mean DSN of the pegfilgrastim arm will be calculated using bootstrap resampling with treatment as the only stratification factor. For the Secondary Efficacy Analyses, the results will each be summarized by treatment arm and cycle. The two-sided 95% CI for the difference between the treatment arms will be calculated. Target Accrual: Approximately 580 patients. Enrollment began January 2016. Contact Information: Spectrum Pharmaceuticals. advance@sppirx.com. Citation Format: Schwartzberg LS, Bharadwaj J, Peguero JA, Vacirca JL, Ibrahim EN, Bhat G, Choi MR, McGregor K, Agajanian R. Randomized phase 3 study of a novel, long-acting G-CSF (eflapegrastim) versus pegfilgrastim in the management of chemotherapy-induced neutropenia in early-stage breast cancer patients receiving docetaxel and cyclophosphamide (TC) (ADVANCE study) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-01-11.

A pharmacokinetic study of lipegfilgrastim in children with Ewing family of tumors or rhabdomyosarcoma

PurposeNeutropenia is a common complication from chemotherapy, limiting optimal dosing and treatment. Lipegfilgrastim is a long-acting granulocyte colony-stimulating factor developed for the management of chemotherapy-induced neutropenia. The objectives of this phase 1, multinational, open-label, single-arm study were to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of a single body weight-adjusted dose of lipegfilgrastim and to evaluate the efficacy, safety, and tolerability of the drug in children with Ewing family of tumors or rhabdomyosarcoma treated with myelosuppressive chemotherapy.MethodsEnrolled patients received lipegfilgrastim (100 µg/kg) 24 h after the last chemotherapy treatment in week 1. Patients were stratified into three age groups: 2 to <6, 6 to <12, and 12 to <18 years. Blood samples for PK analyses were obtained at baseline and at 3, 8, 24, 30, 48, 72, 96, 144, and 240 h postdose for the two oldest groups and up to 144 h in the youngest group.ResultsTwenty-one patients were enrolled and received lipegfilgrastim, seven in each age group. Lipegfilgrastim exposure levels were comparable across age groups, with concentrations maintained over a prolonged period after a single injection. Differences in PD were mainly associated with chemotherapy type. Most investigator-reported adverse events were attributed to chemotherapy and not to lipegfilgrastim. Severe adverse events were noted in 57% of patients; febrile neutropenia, leukopenia, neutropenia, and thrombocytopenia were more frequent among the oldest patients.ConclusionsResults support the use of a body weight-adjusted dose to achieve equivalent initial peak exposure levels of lipegfilgrastim in children of various ages.

Neutropenia inducida por quimioterapia: el punto de vista del oncólogo

Chemotherapy-induced neutropenia is a frequent and serious complication of the oncological treatment. One of its consequences is the interruption of the cytotoxic treatment, which affects the patient response and quality of life, as well as increasing the cost of medical care. Management of chemotherapy-induced neutropenia must include preventive and therapeutic strategies, which the oncologist must take into account when considering the potential myelosuppressive agent and to implement the appropriate treatment approaches. Granulocyte colony stimulating factors are the cornerstone for the management of this complication and have become quite effective treatment tools.

Abstract OT3-02-13: Randomized phase 3 study of a novel, long-acting G-CSF (SPI-2012) versus pegfilgrastim in the management of chemotherapy-induced neutropenia in early-stage breast cancer patients receiving docetaxel and cyclophosphamide (TC) (ADVANCE study)

Abstract Background: SPI-2012 is a distinct biologic that uses the innovative, proprietary long-acting protein/peptide discovery technology (LAPSCOVERY™) to enhance the activity of G-CSF. SPI-2012 consists of a novel, modified recombinant human G-CSF conjugated to the Fc fragment of IgG4 via a polyethylene glycol linker to produce a new, more potent, longer-acting G-CSF with a potentially unique distribution to areas rich in Fc receptors. The primary endpoint of this Phase 3 study is to compare the efficacy of a single dose of SPI-2012 with pegfilgrastim in patients with early-stage breast cancer (ESBC) receiving TC chemotherapy, as measured by the Duration of Severe Neutropenia (DSN) in Cycle 1. Key secondary objectives include the comparison of SPI-2012 with pegfilgrastim during Cycle 1 in: Time to Absolute Neutrophil Count (ANC) Recovery; Depth of ANC Nadir and Incidence of Febrile Neutropenia. Safety and pharmacokinetics will also be assessed. Trial Design: This is a randomized, open-label, active-controlled, multicenter study comparing the efficacy and safety of SPI-2012 to pegfilgrastim. Patients (n=506) will be randomized in a 1:1 ratio to receive either SPI-2012 (equivalent to 3.6 mg G-CSF) or pegfilgrastim (equivalent to 6.0 mg G-CSF) once per chemotherapy cycle (up to 4 cycles), approximately 24 hrs after chemotherapy. Eligibility Criteria: This study will enroll histologically confirmed ESBC patients who are eligible to receive adjuvant or neoadjuvant TC chemotherapy and at least 18 years of age, with adequate hematologic, renal and hepatic function. Patients will be excluded if they have active concurrent malignancy or life-threatening disease; a known sensitivity or previous reaction to E. coli derived products or any of the products to be administered during study participation; concurrent adjuvant cancer therapy; locally recurrent/metastatic or contralateral breast cancer; previous exposure to filgrastim, pegfilgrastim, or other G-CSF products in clinical development prior to the administration of study drug; bone marrow or hematopoietic stem cell transplant or radiation therapy prior to enrollment or are pregnant or breast-feeding. Statistical Methods: The goal of the study is to demonstrate non-inferiority of SPI-2012 to pegfilgrastim. For the Primary Efficacy Analysis, the mean DSN in Cycle 1 will be compared between the SPI-2012 and pegfilgrastim treatment arms. A 2-sided 95% confidence interval (CI) of the difference between the mean DSN of the SPI-2012 arm and the mean DSN of the pegfilgrastim arm will be calculated using bootstrap resampling with treatment as the only stratification factor. For the Secondary Efficacy Analyses, the results will each be summarized by treatment arm and Cycle. The two-sided 95% CI for the difference between the treatment arms will be calculated. Target Accrual: Approximately 506 pts. Citation Format: Schwartzberg L, Vacirca JL, Hager SJ, Adoo CS, Ibrahim EN, Bhat G, Choi MR, Allen LF, Tedesco KL, Agajanian R. Randomized phase 3 study of a novel, long-acting G-CSF (SPI-2012) versus pegfilgrastim in the management of chemotherapy-induced neutropenia in early-stage breast cancer patients receiving docetaxel and cyclophosphamide (TC) (ADVANCE study). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-02-13.

Role of lipegfilgrastim in the management of chemotherapy-induced neutropenia.

Chemotherapy, irradiation, and other agents are widely used to target the process of cell division in neoplastic cells. However, while these therapies are effective against most cancers, the high proliferative rate of the cells of the hematopoietic system that produce billions of blood cells needed daily throughout life is extremely sensitive to these agents, resulting in loss of blood cell populations, which can be life threatening. Neutropenia is the most serious hematologic toxicity of chemotherapy, which can result in patient morbidity and mortality due to opportunistic infection and often is the limiting factor in dose escalation or duration of chemotherapeutic administration. Neutropenic patients often require hospitalization and incur substantial medical costs associated with anti-infective therapy. Treatment of iatrogenic and congenic neutropenia was changed in the early 1990s with the introduction of filgrastim (Neupogen®) and pegfilgrastim (Neulasta®). With the expiration of patent lives of both of these drugs, biosimilars have begun to emerge. In this review, we will summarize the chemical characteristics, pharmacokinetics, safety and efficacy of lipegfilgrastim (Lonquex®), the first long-acting biosimilar filgrastim to receive regulatory approval and enter the marketplace.

Management of chemotherapy-induced neutropenia: measuring quality, cost, and value.

Treatment-associated neutropenia continues to represent the most common dose-limiting toxicity of cancer chemotherapy. It often leads to fever and infection, prompting hospitalization and occasionally resulting in serious morbidity, and even mortality, despite modern broad-spectrum antibiotic treatment and supportive care. Neutropenia and its complications may also lead to chemotherapy dose reductions, treatment delays, or early treatment termination, compromising disease control and the potential for cure. NCCN Clinical Practice Guidelines in Oncology recommend administration of primary prophylaxis with a myeloid growth factor in patients receiving regimens associated with a high risk for febrile neutropenia, and consideration of prophylaxis in patients receiving lower-risk regimens who have other risk factors that might place them at higher risk for febrile neutropenia. Although these agents have been shown to be effective and safe in numerous randomized controlled trials, they are expensive and contribute significantly to increasing health care costs. Regulatory agencies and guideline organizations do not currently address the issue of cost. However, with the relentless increase in health care use and current efforts to reform health care, it has become increasingly important to assess both the cost and the net benefit of interventions related to an episode of care in order to compare the overall value of therapeutic options. This article defines and discusses the intersection of quality, costs, and value in the context of prophylactic myeloid growth factor use in patients with cancer receiving myelosuppressive chemotherapy.

Management of Chemotherapy-Induced Neutropenia: Opportunities for Pharmacist Involvement

Purpose This article highlights the clinical impact of chemotherapy-induced neutropenia (CIN) and reviews the clinical evidence supporting the updated guideline recommendations from leading scientific organizations that focus on cancer care regarding the use of myeloid growth factors to reduce the incidence of febrile neutropenia (FN) from chemotherapy. The aim is to provide insight for practicing pharmacists regarding how they can be more proactive in developing best-practice strategies for the management of CIN as well as the prevention of FN. Summary CIN, the primary dose-limiting toxicity of chemotherapy, is common in many tumor types that are treated with myelosuppressive chemotherapy and occurs with the greatest frequency in the first cycle of treatment. Treatment with myeloid growth factors, or colony-stimulating factors (CSFs), has shown to be effective in reducing the risk, severity, and duration of FN from chemotherapy. Despite recent revisions to various clinical guidelines that have resulted in alignment on the recommendation for prophylactic CSF use in patients with a greater than or equal to 20% risk of developing FN, a gap remains between actual clinical usage and best practice. Pharmacists are key members of multidisciplinary health care teams and are uniquely positioned to evaluate current practice and develop strategies that ensure appropriate CSF use. This paper summarizes the recent changes to CSF guidelines, reviews clinical data that support those changes, and discusses strategies for pharmacist involvement in the management of CIN and FN prevention using real-world examples of improvement initiatives. Conclusion Neutropenia is a dose-limiting toxicity of chemotherapy that has significant implications for effective cancer treatment and patient health outcomes. Pharmacists are uniquely positioned to perform various interventions, which help ensure appropriate CSF use and improve the management of CIN.

Management of Chemotherapy-induced Neutropenia with Colony-stimulating Factors

Management of Chemotherapy-induced Neutropenia with Colony-stimulating Factors

Granulocyte colony-stimulating factors in the management of chemotherapy-induced neutropenia: evidence based review

(1) Neutropenia is a frequent complication of chemotherapy associated with life-threatening infections, hospitalisation, and chemotherapy dose reductions and delays.(2) Primary prophylaxis with granulocyte colony-stimulating factors has been shown to reduce the incidence and duration of neutropenia, febrile neutropenia, infections, hospitalisation and antibiotic use.(3) Recent randomised clinical trials of filgrastim, lenograstim and pegfilgrastim showed variable results across patient groups at different risks of febrile neutropenia.(4) Pegfilgrastim is at least as effective as filgrastim in the prophylaxis of chemotherapy-induced neutropenia and has improved pharmacokinetics requiring reduced administration.

Anglo-Celtic Cooperative Oncology Group (ACCOG)

This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by Anglo-Celtic Cooperative Oncology Group (ACCOG). Clinical trials include: Intensive chemotherapy for high-risk (&gt;4 axillary lymph nodes) breast cancer. Study Anglo Celtic IA randomised comparative trial of Adriamycin and Taxotere versus Adriamycin and Cyclophosphamide as primary therapy for patients with potentially operable disease &gt;3cm diameter, locally advanced or inflammatory breast cancer. Study Anglo Celtic IIProspective randomized comparison of G-CSF (filgrastim) secondary prophylaxis versus conservative management of chemotherapy-induced neutropenia to maintain dose intensity in chemotherapy for breast cancer. Study Anglo Celtic IIIA randomized 2-arm, prospective, multi-centre, open label phase III trial comparing the activity and safety of a weekly versus a 3-weekly paclitaxel treatment schedule in patients with advanced or metastatic breast cancer. Study Anglo Celtic IV “Will Weekly Win”, www.taxol-uk.comOvarian protection trial in oestrogen non-responsive premenopausal breast cancer patients receiving adjuvant or neo-adjuvant chemotherapy. Anglo Celtic V – OPTION

Neutropenia management with granulocyte colony-stimulating factors: From guidelines to nursing practice protocols

Neutropenia, a problem that oncology nurses face in daily practice, is the major dose-limiting toxicity in patients with cancer who are treated with myelosuppressive chemotherapy. The incidence of chemotherapy dose reductions or treatment delays, which can impact overall dose intensity and compromise treatment outcomes, may be reduced by the proactive use of granulocyte colony-stimulating factor (G-CSF). National and international guidelines have been developed to promote the cost-effective use of G-CSF. Nursing care protocols for the management of chemotherapy-induced neutropenia (CIN) can be developed based on the national guidelines and modified for use by individual clinical practices. Risk assessment for CIN, which considers the prescribed chemotherapy regimen, patient risk factors, and treatment intent, should be a key component of the practice guidelines. Because most neutropenic events occur in the first cycle of chemotherapy, risk assessments should be conducted before the initiation of chemotherapy. Patients identified as at high risk for neutropenic complications should be given G-CSF in the first and subsequent cycles to allow the delivery of chemotherapy at full dose and on schedule. Nurses are instrumental in the development and implementation of neutropenia management protocols, which have the potential to markedly improve the quality of care and outcomes for patients with cancer.