Efficacy and safety of PEG-rhG-CSF versus rhG-CSF in preventing chemotherapy-induced-neutropenia in early-stage breast cancer patients.

BACKGROUND: To compare the clinical value of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and pegylated rhG-CSF(PEG-rhG-CSF) in early-stage breast cancer (EBC) patients receiving adjuvant chemotherapy, compare the efficacy of PEG-rhG-CSF with different dose and explore the timing of rhG-CSF rescue treatment. METHODS: Patients in two PEG-rhG-CSF subgroups were given 3 mg or 6 mg PEG-rhG-CSF within 24 ~ 48 h after chemotherapy for preventing myelosuppression, while patients in the rhG-CSF group were given rhG-CSF. Observation indicators include the incidence of febrile neutropenia (FN) and grade 3/4 chemotherapy-induced-neutropenia (CIN), the overall levels and nadir values of white blood cells (WBC) and absolute neutrophil count (ANC), comparison of WBC and ANC curves over time, the incidence of CIN-related complications, the incidence of adverse events in each group and the timing of rescue treatment for rhG-CSF. RESULTS: There was no significant difference in the incidence of FN in the first cycle among the groups (P = 0.203). But the incidence of ≥ 3 grade CIN in two PEG-rhG-CSF subgroups was significantly lower than that in the rhG-CSF group (P < 0.001). The overall WBC and ANC levels in the PEG-rhG-CSF group were significantly higher than those in the rhG-CSF group (P < 0.001). In terms of CIN-related complications, less chemotherapy delay rate (1.1 vs. 7.5%, P = 0.092), less dose reduction rate (6.9 vs. 7.5%, P = 1.000), less antibiotic use rate (3.4 vs. 17.5%, P = 0.011) and less proportion of rhG-CSF rescue therapy (24.1 vs. 85.0%, P < 0.001) in the PEG-rhG-CSF group, and there were no significant differences between PEG-rhG-CSF subgroups. In the incidence of adverse events among the groups, there were no statistical differences. All patients undergoing rhG-CSF rescue treatment were mainly 4 grade (63.6%) and 3 grade (25.5%) CIN, and 10.9% of patients with 1 ~ 2 grade CIN who had high infection risk or had been infected. CONCLUSION: PEG-rhG-CSF has better efficacy and equal tolerance compared with rhG-CSF in preventing CIN in EBC patients receiving EC regimen. Moreover, a half-dose 3 mg PEG-rhG-CSF also had good efficacy. Last, patients with ≥ 3 grade CIN and others who have been assessed to be at high risk of infection or have co-infection should consider rhG-CSF or even antibiotic rescue treatment.

A prospective, randomized clinical trial of emergency treatment of chemotherapy-induced neutropenia and febrile neutropenia by pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF).

AIMS: As one of the mainstays of breast cancer therapy, chemotherapy inevitably induces neutropenia. In this study, we explored the role of PEG-rhG-CSF (pegylated recombinant human granulocyte colony-stimulating factor) in the emergency treatment of chemotherapy-induced grades 3-4 neutropenia. METHODS: A total of 100 patients with breast cancer were randomized (1:1) into the study. Fifty patients randomized to the experimental group were treated with PEG-rhG-CSF after grades 3-4 neutropenia following the first cycle of chemotherapy, while 50 patients randomized to the control group received a daily injection of rhG-CSF (recombinant human granulocyte colony-stimulating factor). The primary endpoint was the recovery time of grades 3-4 neutropenia. RESULTS: Compared with patients in the control group, the mean ± SD recovery time of grades 3-4 neutropenia and febrile neutropenia (FN) was significantly shorter for patients in the experimental group (grades 3-4, P = .000; grade 4, P = .000; FN, P = .038). There is no significant difference in the incidence of FN for the two groups. In the experimental group, the duration of grades 3-4 neutropenia in patients aged <60 years and ≥60 years was 2.15 and 3.20 days, respectively (P = .037). Adverse events (AEs) of any grade were reported in 37 (75.5%) and 28 (59.6%) patients from the two groups, respectively. No grade ≥3 AEs were reported. CONCLUSION: This study supported that the PEG-rhG-CSF was more effective and convenient than rhG-CSF for treating grades 3-4 neutropenia and FN in patients with breast cancer and had manageable toxicity.

Safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor during concurrent chemoradiotherapy for small-cell lung cancer: a retrospective, cohort-controlled trial.

OBJECTIVE: To investigate pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) safety and efficacy in preventing hematological toxicity during concurrent chemoradiotherapy (CCRT) for small-cell lung cancer (SCLC). METHODS: We retrospectively assessed 80 SCLC patients treated with CCRT from January 2013 to December 2018 who received PEG-rhG-CSF within 48 hours after the end of chemotherapy, defined as prophylactic use, as the experimental group. An additional 80 patients who were not treated with PEG-rhG-CSF were matched 1:1 by the propensity score matching method and served as the control group. The main observations were differences in hematological toxicity, neutrophil changes, febrile neutropenia (FN) incidence and adverse reactions. Progression-free survival (PFS) and overall survival (OS) were analyzed with regular assessment and follow-up. RESULTS: The leukocyte, neutrophil, erythrocyte, and platelet counts and hemoglobin level decreased after CCRT, but the experimental group had slightly higher leukocyte and neutrophil counts than the control group (P < 0.05). The incidences of grade III-IV leukopenia (18.75% vs. 61.25%) and neutropenia (23.75% vs. 67.5%) in the experimental group were significantly lower than those in the control group (P < 0.05). The absolute neutrophil count was 4.17 ± 0.79 (× 109/L) on day 1 and peaked 6.81 ± 2.37 (× 109/L) on day 10 in the experimental group; the value in the control group was 2.81 ± 0.86 (× 109/L) on day 1. It decreased significantly and reached the minimum 0.91 ± 0.53 (× 109/L) on day 10 (P < 0.05). The experimental group had a lower FN incidence than the control group (P < 0.05). There was also no significant acute esophagitis or pulmonary toxicity. The treatment had no significant effect on PFS (11.4 months vs. 8.7 months, P = 0.958) or OS (23.9 months vs. 17.3 months, P = 0.325) over an 18.6-month median follow-up time. CONCLUSION: PEG-rhG-CSF has good efficacy and safety in preventing hematological toxicity in SCLC patients during CCRT and has no significant effects on PFS or OS.

Pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor in children with acute leukaemia.

AIMS: This open-label, phase I study evaluated the pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for the treatment of chemotherapy-induced neutropenia in children with acute leukaemia. METHODS: PEG-rhG-CSF was administered as a single 100 mcg/kg (3 mg maximum dose) subcutaneous injection at the end of each chemotherapy period when neutropenia occurred. Blood samples were obtained from patients treated with PEG-rhG-CSF. PEG-rhG-CSF serum concentrations were determined by an enzyme-linked immunosorbent assay. Population pharmacokinetic (PPK) analysis was implemented using the nonlinear mixed-effects model. Short-term safety was evaluated through adverse events collection (registered at clinicaltrials.gov identifier: 03844360). RESULTS: A total of 16 acute leukaemia patients (1.8-13.6 years) were included, of whom two (12.5%) had grade 3 neutropenia, six (37.5%) had grade 4 neutropenia, and eight (50.0%) had severe neutropenia. For PPK modelling, 64 PEG-rhG-CSF serum concentrations were obtainable. A one-compartment model with first-order elimination was used for pharmacokinetic data modelling. The current weight was a significant covariate. The median (range) of clearance (CL) and area under the serum concentration-time curve (AUC) were 5.65 (1.49-14.45) mL/h/kg and 16514.75 (6632.45-54423.30) ng·h/mL, respectively. Bone pain, pyrexia, anaphylaxis and nephrotoxicity were not observed. One patient died 13 days after administration, and the objective assessment of causality was that an association with PEG-rhG-CSF was "possible". CONCLUSIONS: The AUC of PEG-rhG-CSF (100 mcg/kg, 3 mg maximum dose) in paediatric patients with acute leukaemia were similar to those of PEG-rhG-CSF (100 mcg/kg) in children with sarcoma. PEG-rhG-CSF is safe, representing an important therapeutic option for chemotherapy-induced neutropenia in paediatric patients with acute leukaemia.

Advantages with prophylactic PEG-rhG-CSF versus rhG-CSF in breast cancer patients receiving multiple cycles of myelosuppressive chemotherapy: an open-label, randomized, multicenter phase III study.

BACKGROUND: PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China's registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. METHODS: In this open-label, randomized, multicenter phase 3 study, breast cancer patients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2-4, the incidence of febrile neutropenia, and the safety. RESULTS: A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3-4, reaching a statistical significance at cycle 4 in either incidence (P = 0.0309) or duration (P = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (P = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (P = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan-Meier analysis (n = 49, P = 0.153). CONCLUSIONS: PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.

A phase I study of different doses and frequencies of pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) in patients with standard-dose chemotherapy-induced neutropenia.

OBJECTIVE: The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) is 100 µg/kg once per cycle for patients receiving intense-dose chemotherapy. However, few data are available on the proper dose for patients receiving less-intense chemotherapy. The aim of this phase I study is to explore the proper dose and administration schedule of PEG rhG-CSF for patients receiving standard-dose chemotherapy. METHODS: Eligible patients received 3-cycle chemotherapy every 3 weeks. No PEG rhG-CSF was given in the first cycle. Patients experienced grade 3 or 4 neutropenia would then enter the cycle 2 and 3. In cycle 2, patients received a single subcutaneous injection of prophylactic PEG rhG-CSF on d 3, and received half-dose subcutaneous injection in cycle 3 on d 3 and d 5, respectively. Escalating doses (30, 60, 100 and 200 µg/kg) of PEG rhG-CSF were investigated. RESULTS: A total of 26 patients were enrolled and received chemotherapy, in which 24 and 18 patients entered cycle 2 and cycle 3 treatment, respectively. In cycle 2, the incidence of grade 3 or 4 neutropenia for patients receiving single-dose PEG rhG-CSF of 30, 60, 100 and 200 µg/kg was 66.67%, 33.33%, 22.22% and 0, respectively, with a median duration less than 1 (0-2) d. No grade 3 or higher neutropenia was noted in cycle 3 in all dose cohorts. CONCLUSIONS: The pharmacokinetic and pharmacodynamic profiles of PEG rhG-CSF used in cancer patients were similar to those reported, as well as the safety. Double half dose administration model showed better efficacy result than a single dose model in terms of grade 3 neutropenia and above. The single dose of 60 µg/kg, 100 µg/kg and double half dose of 30 µg/kg were recommended to the phase II study, hoping to find a preferable method for neutropenia treatment.

The Effectiveness and Optimal Timing of PEG-rhG-CSF After Autologous Peripheral Blood Stem Cell Transplantation: A Multicenter Experience.

No consensus has been made on the use of PEG-modification recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in patients receiving autologous peripheral blood stem cell transplantation (PBSCT). To evaluate the efficacy and safety of PEG-rhG-CSF in provision of neutrophil support for lymphoma patients receiving autologous PBSCT. This retrospective study included lymphoma patients receiving either PEG-rhG-CSF or rhG-CSF after autologous PBSCT from 2018 to 2021 in two clinics. Hematologic recovery time, incidence of infectious complications and toxicity were compared between these two rhG-CSFs and among different initiation time of PEG-rhG-CSF. Of the 139 subjects included, 93 received PEG-rhG-CSF and 46 received rhG-CSF after transplantation. Compared with rhG-CSF, PEG-rhG-CSF marginally but significantly accelerated the neutrophil engraftment by 1 day (10 vs. 9 days, respectively) with no increasing on the risk of infectious complication and toxicity. In the PEG-rhG-CSF group, 50 patients received the growth factor on day 1, 19 received on day 3 and 24 received on day 5. The neutrophil engraftment was significantly shorter in day 1 and day 3 subgroup (9, 9, and 10 days, respectively), with a lower incidence of febrile neutropenia (82%, 100%, 100%) and documented infections (76%, 100%, 100%) in day 1 subgroup. PEG-rhG-CSF might be an alternative to rhG-CSF for lymphoma patients received autologous PBSCT. Administrating PEG-rhG-CSF on day 1 can achieve both faster hematologic recovery and lower infectious complications. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01704-8.

PEG-rhG-CSF for prophylaxis of neutropenia after chemotherapy in patients with non-small cell lung cancer: A multicenter, prospective, randomized study.

BACKGROUND: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing neutropenia during multiple cycles of chemotherapy in patients with non-small cell lung cancer (NSCLC). METHOD: In a multicenter, prospective, randomized trial, patients with NSCLC were randomly assigned in a 2:1 ratio to treatment group (PEG-rhG-CSF as primary prophylactic therapy) or control group. Patients in the control group were administered rhG-CSF when white blood cell count was <2.0 × 109 /L or absolute neutrophil count <1.0 × 109 /L. The primary endpoint was the incidence of grade 3/4 neutropenia. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia in each cycle, the incidence of febrile neutropenia (FN), delay rate of chemotherapy, prolonged time of chemotherapy, and safety. RESULTS: Between January 2019 and July 2021, 130 patients were enrolled (treatment group: n = 87, control group: n = 43). The incidence of grade 3/4 neutropenia in the treatment group was significantly lower than that in the control group (1.15% vs. 11.63%, p < 0.05). The mean duration of grade 3/4 neutropenia for the treatment and control group was 2.00 and 3.75 days, respectively. There were no statistical differences in the incidence of FN, delay rate of chemotherapy, prolonged time of chemotherapy, and antibiotic use between the two groups (all p > 0.05). Adverse events were reported in 47.13% of patients in the treatment group and 48.84% patients in the control group. CONCLUSIONS: Primary prophylactic treatment with PEG-rhG-CSF could reduce the incidence of neutropenia in patients with NSCLC during multiple cycles of chemotherapy, with acceptable safety and tolerability.

Efficacy and Safety for the Use of Half-Dosed Pegylated Granulocyte Colony-Stimulating Factors in Preventing Febrile Neutropenia During Chemotherapy in Patients With Malignant Tumors: A Multicenter, Open-Labeled, Single-Arm Phase 2 Trial.

Background: Prophylactic granulocyte-colony stimulating factor (G-CSF) has been shown to effectively prevent febrile neutropenia (FN) and grade 3/4 neutropenia during myelosuppressive treatment. The present study reports the clinical efficacy and safety of the prophylactic use of G-CSF with a half dose for cancer patients with an intermediate risk of FN combined with ≥1 patient-specific risk during multiple chemotherapy. Methods: This multicenter, one-arm, and open-label clinical study involved 151 patients [median age, 54 years old (range, 46.0-62.5); 38.4% female] with malignant tumors, including >20 different cancers. These patients underwent a total of 604 cycles of chemotherapy and received a half dose of PEG-rhG-CSF administration prior to each cycle. Results: The incidence rate of FN was 3.3% for this cohort during chemotherapy. Chemotherapy delay occurred in 6 (4.0%) patients for 12 (2.0%) cycles. Early termination of cancer treatment occurred in 14 (9.3%) patients. In this cohort, 23 (15.2%) patients required antibiotic use during courses of chemotherapy. A total of 28 (18.5%) patients experienced clear adverse effects during cancer treatment. Conclusion: The prophylactic PEG-rhG-CSF with a half dose can both efficaciously and safely prevent neutropenia for patients of diverse cancers with an intermediate risk of FN combined with ≥1 patient-specific risk during chemotherapy.

Safety and efficacy of administering reduced doses of pegylated recombinant human granulocyte-colony stimulating factors in patients treated with cisplatin and etoposide for small cell carcinoma: A retrospective study.

BACKGROUND: The aim of this study was to discuss the safety and efficacy of administering reduced doses (3 mg) of pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF) at approximately 24 h or up to three days following treatment with etoposide and cisplatin (EP). METHODS: A total of 104 cycles from 31 patients were divided into a PEG-rhG-CSF prophylaxis group (PP-Group) and a control group (No-PP-Group). The PP-Group received a reduced dose of 3 mg of PEG-rhG-CSF within a minimum of 15 h and a maximum of 72 h following EP chemotherapy, while the rest did not receive any G-CSF prophylaxis (No-PP-Group). For both groups, complete blood counts, incidence of febrile neutropenia (FN), grade III or IV neutropenia, and the use of antibiotics to treat neutropenia were recorded. RESULTS: There was statistically no significant difference in the incidence of FN (0% vs. 1.4%, p = 1), antibiotic use due to neutropenia (0% vs. 2.7%, p = 0.881), estimated lowest mean marginal (EM) platelet (106.56 × 109 /L vs. 127.70 × 109 /L, p = 0.056) and hemoglobin (110.48 g/L vs. 110.14 g/L, p = 0.906) levels between the two groups. However, when compared with the No-PP-group, the white blood cell count in the PP-group was significantly higher (EM means: 4.95 × 109 /L vs. 2.80 × 109 /L, p < 0.01), while the incidence of grade III or IV neutropenia was significantly lower (9.1% vs. 68.1%, p < 0.01). CONCLUSIONS: The administration of a low dose (3 mg) of PEG-rhG-CSF within approximately 24 h or up to three days following EP treatment is safe and effective at reducing the risk of neutropenia. These findings bring a more flexible administration interval between PEG-rhG-CSF and EP treatment.

Clinical efficacy and safety of mecapegfilgrastim in small cell lung cancer as primary prophylaxis of neutropenia post chemotherapy: a retrospective analysis.

BACKGROUND: Neutropenia is the most common adverse reaction seen in small cell lung cancer after chemotherapy. Febrile neutropenia (FN) leads to an increase in hospitalizations and may even be life-threatening. This paper aims to investigate the efficacy and adverse reactions of mecapegfilgrastim in the primary prophylaxis of neutropenia in patients with small cell lung cancer after receiving intermediate risk chemotherapy with at least one patient risk factor. METHODS: The clinical records of 106 patients with small cell lung cancer admitted to Zhejiang Cancer Hospital from June 2019 to January 2021 were retrospectively analyzed. Patients were divided into a mecapegfilgrastim [pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF)] group and control group, each with 53 patients. The mecapegfilgrastim group received subcutaneous injection of mecapegfilgrastim 24 hours after the first cycle of chemotherapy, while the control group did not receive this. The Chi-square (χ2) test or Fisher exact test were used to compare the incidence of neutropenia, FN, and the proportion of patients administrated with full dose chemotherapy in the two groups after the first cycle of chemotherapy. Data on adverse events after mecapegfilgrastim were also collected. RESULTS: After the first cycle of chemotherapy, the incidence of neutropenia in the mecapegfilgrastim group was significantly lower than that in the control group (P=0.001) and the incidence of FN in the mecapegfilgrastim group was lower than that in the control group (P=0.118). The proportion of patients administrated with full-dose chemotherapy in the mecapegfilgrastim group was significantly higher than that in the control group (P=0.001). The main adverse reactions to mecapegfilgrastim were muscle pain, fever, and fatigue. CONCLUSIONS: After receiving intermediate risk chemotherapy, the incidence of neutropenia was significantly reduced by the primary prophylaxis of mecapegfilgrastim in patients with small cell lung cancer. The adverse events of mecapegfilgrastim were mild and tolerable, and included muscle pain, fever, and fatigue.

Cost-Effectiveness Analysis of PEG-rhG-CSF as Primary Prophylaxis to Chemotherapy-Induced Neutropenia in Women With Breast Cancer in China: Results Based on Real-World Data.

Background: Pegylated recombinant human granulocyte colony-stimulating factors (PEG-rhG-CSFs) are more commonly and widely used than recombinant human granulocyte colony-stimulating factors (rhG-CSFs) in preventing chemotherapy-induced neutropenia in patients with stage II-IV breast cancer. To reduce the financial burden on these patients, the corresponding medical insurance directory needs to be revised. Objectives: To evaluate the cost-effectiveness of PEG-rhG-CSF versus rhG-CSF in patients with stage II-IV breast cancer in central China. Methods: Two Markov models, a chemotherapy model and a post-chemotherapy model, were developed to study the effects and costs, with a time horizon of 12 weeks and 35 years, respectively. Cost and probability input data were primarily obtained from a retrospective real-world study conducted in five tertiary hospitals. Propensity score matching was adopted to overcome retrospective bias. Other parameters were extracted from literature as well as advice from clinical experts. Univariate and probabilistic sensitivity analyses were conducted. Results: In the first chemotherapy model, PEG-rhG-CSF was associated with fewer episodes of febrile neutropenia (FN) (N = 19 per 1000 patients treated), infections (N = 24 per 1000 patients treated) and deaths (N = 2 per 1000 patients treated), but higher costs (¥36 more per patient treated). The post-chemotherapy model indicated that PEG-rhG-CSF led to higher gains in quality-adjusted life years (QALYs) (11.695 versus 11.516) in comparison to rhG-CSF. Sensitivity analysis showed that the cost of PEG-rhG-CSF had the greatest impact on the incremental costs, and incremental QALYs were very sensitive to the risk of RDI <85%. The probability of PEG-rhG-CSF being cost-effective compared to rhG-CSF was 66% at the willingness to pay (WTP) thresholds of ¥72,371 per QALY gained. Conclusion: According to this economic evaluation based on real-world data, PEG-rhG-CSF may be considered as a more cost-effective strategy relative to rhG-CSF for stage II-IV breast cancer patients in central China. However, to reflect a national perspective, further evidence is needed using data from larger-scale studies.

Clinical application value of pegylated recombinant human granulocyte-colony stimulating factor in neutropenia after chemotherapy / 中国生物制品学杂志

@#During chemotherapy of malignant tumors,neutropenia is the most important adverse event caused by myelosuppressive chemotherapeutics,of which the degree and duration are closely related to the risk of infection and even death.Granulocyte-colony stimulating factor(G-CSF) is an endogenous hematopoietic growth factor that can stimulate the proliferation and differentiation of neutrophil precursors,and increase the survival rate and activity of mature neutrophils.Recombinant human granulocyte-colony stimulating factor(rhG-CSF) is an artificially synthesized cytokine with G-CSF biological activity.It is used clinically for the prevention and treatment of neutropenia after treatment with cytotoxic chemotherapeutics,requiring multiple medications and repeated injections during application for its short half-life.Pegylated recombinant human granulocyte-colony stimulating factor(PEG-rhG-CSF) is its long-acting dosage form,and patients only need to be administered once per cycle of chemotherapy,which has been widely used in clinical practice because of its stability and convenience.This paper systematically described the clinical application value of PEG-rhG-CSF in neutropenia after chemotherapy,aiming to provide a reference for its further clinical application.

Effect of preventive application of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) during concurrent chemoradiotherapy in patients with lung cancer / 中华放射医学与防护杂志

Objective:To evaluate the effect of preventive application of PEG-rhG-CSF on the prevention of neutropenia during concurrent chemoradiotherapy in patients with lung cancer.Methods:A total of 149 patients with lung cancer who received concurrent chemoradiotherapy at Peking University Cancer Hospital from April 2020 to April 2021 were retrospectively analyzed. There were 79 cases in the prevention group, including 48 cases of primary prevention group (preventive application of PEG-rhG-CSF in all concurrent chemoradiotherapy cycles) and 31 cases of secondary prevention group (preventive application of PEG-rhG-CSF in the concurrent chemoradiotherapy cycles after neutropenia occurred). There were 70 cases in non-prevention group. The incidence of grade 3-4 neutropenia, the completion rate of concurrent chemoradiotherapy, the rate of chemoradiotherapy dose reduction and treatment delay, and the rate of hematological toxicities related hospitalization were compared between the prevention group and the non-prevention group.Results:The incidence of grade 3-4 neutropenia in the whole group was 32.2% (48/149), including 6.3% (3/48) in the primary prevention group, 9.7% (3/31) in the secondary prevention group, and 35.7% (25/70) in the non-prevention group. The difference was statistically significant ( χ2=17.81, P<0.001) in the incidence of grade 3-4 neutropenia. The incidence of febrile neutropenia was 3.4% (5/149) in the whole group, but none of them occurred in the primary prevention group. The full completion rate of concurrent chemotherapy was 96.2% (76/79) in the prevention group, which was significantly higher than 82.9% (58/70) in the non-prevention group ( χ2=7.30, P=0.007). The incidence of treatment delayed and dose reduction of chemoradiotherapy was 19.0% (15/79) in the prevention group and 40.0% (28/70) in the non-prevention group, and the difference was statistically significant ( χ2=7.98, P=0.005). Conclusions:The preventive application of PEG-rhG-CSF can effectively reduce the incidence of neutropenia and better ensure the concurrent chemoradiotherapy in lung cancer patients on schedule.

Effect of PEG-rhG-CSF in Preventing Chemotherapy-induced Neutropenia in Locally Advanced Non-small Cell Lung Cancer Patients at Nutritional Risk / 肿瘤防治研究

Objective To explore the efficacy and safety of polyethylene glycol recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in locally advanced non small cell lung cancer (NSCLC) patients at nutritional risk. Methods A total of 337 locally advanced NSCLC patients at nutritional risk were selected. They were randomly divided into three groups: 112 cases in the non-prophylactic drug group (control group), 112 cases in the prophylactic use of rhG-CSF treatment group (rhG-CSF group), and 113 cases in the prophylactic use of PEG-rhG-CSF treatment group (PEG-rhG-CSF group). The incidence and duration of neutropenia after chemotherapy and the ratio of CD4+/CD8+T cells in peripheral blood were observed. Results The incidences of neutropenia in the control group, rhG-CSF group, and PEG-rhG-CSF group were 67.97%, 41.57%, and 38.98% (P < 0.05), respectively. The incidences of grade Ⅲ-Ⅳ neutropenia in the three groups were 22.39%, 14.25%, and 11.14% (P < 0.05); moreover, the incidence of febrile neutropenia in the three groups was 3.55%, 1.84%, and 1.21% (P < 0.05); in addition, the ratios of CD4+/CD8+T cells in peripheral blood were 1.27±0.44, 1.41±0.52, and 1.49±0.42 (P < 0.05). The duration of grade Ⅲ-Ⅳ neutropenia and the time required for the neutrophil value to reach 2.0×109/L from the lowest value in the PEG-rhG-CSF group were lower than those in the control and rhG-CSF groups (P < 0.05). Conclusion The PEG-rhG-CSF preventive treatment used in the course of chemoradiotherapy in locally advanced NSCLC patients at nutritional risk can reduce the incidence of neutropenia and improve immunologic function. PEG-rhG-CSF preventive treatment is worthy of clinical recommendation.

A Randomized Multicenter Phase III Study of Single Administration of Mecapegfilgrastim (HHPG-19K), a Pegfilgrastim Biosimilar, for Prophylaxis of Chemotherapy-Induced Neutropenia in Patients With Advanced Non-Small-Cell Lung Cancer (NSCLC).

BACKGROUND: Mecapegfilgrastim (code name HHPG-19K) is a biosimilar to pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF). The efficacy and safety of mecapegfilgrastim, using a regimen of once-per-cycle injection of 100-µg/kg or a fixed 6-mg dose, were evaluated for the prophylactic therapy for neutropenia in patients with advanced non-small-cell lung cancer (NSCLC) who were treated with myelosuppressive chemotherapy. MATERIALS AND METHODS: Patients were randomized (1:1:1) blindly to 3 treatment arms to receive a single injection of mecapegfilgrastim 100 µg/kg, a 6-mg fixed dose of mecapegfilgrastim, or saline (control) in cycle 1. In cycles 2 to 4 following unblinding at the end of cycle 1, patients in the control arm received daily injections of short-acting rhG-CSF at a dose of 5 µg/kg, whereas patients in the 2 mecapegfilgrastim arms continued the same treatment as in cycle 1. All patients received 4 chemotherapy cycles of docetaxel combined with cisplatin or carboplatin every 21 days. The primary endpoint was the incidence of grade ≥ 3 neutropenia in cycle 1. RESULTS: A single dose of 100 µg/kg or a fixed 6-mg dose of mecapegfilgrastim per cycle effectively reduced chemotherapy-induced neutropenia and was comparable to daily rhG-CSF with regard to all efficacy endpoints, including incidence of grade ≥ 3 neutropenia, incidence of febrile neutropenia, duration of grade ≥ 3 neutropenia, and time to neutrophil recovery. No difference in efficacy parameters was observed between the 2-dose regimens of mecapegfilgrastim across all cycles. Mecapegfilgrastim was well-tolerated and was as safe as daily rhG-CSF. CONCLUSION: Once-per-cycle injection of mecapegfilgrastim is as effective and safe as daily rhG-CSF for prophylaxis of chemotherapy-induced neutropenia in patients with NSCLC. Mecapegfilgrastim (fixed 6-mg dose) is recommended in clinical practice for its convenient dose management.

Clinical analysis of the use of PEG-rhG-CSF after chemotherapy in patients with soft tissue sarcoma / 肿瘤

Objective: To analyze the clinical effect of prophylactic use of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) after chemotherapy in patients with soft tissue sarcoma. Methods: The clinical data of the patients with soft tissue sarcoma who were diagnosed in the Oncology Department of Zhongshan Hospital Affiliated to Fudan Universtiy from July 2016 to July 2019, and received the preventive treatment of PEG-rhG-CSF after chemotherapy to prevent the increase of leukocyte count in vivo, was collected and analyzed. Results: A total of 107 patients with soft tissue sarcoma were treated with PEG-rhG-CSF after chemotherapy. The incidence of neutropenia was 48.6% (52/107), in which the incidence of grade 3-4 neutropenia was 28.0% (30/107), and the incidence of febrile neutropenia (FN) was 4.7% (5/107). The incidence of neutropenia in male or female patients was 52.8% (28/53) or 44.4% (24/54), respectively; there was no significant difference (P > 0.05). The incidence of neutropenia in elderly patients (≥ 65 years old) or young and mid-aged patients ( 0.05). The use of IA chemotherapy with ifosfamide and doxorubicin was more toxic, the incidence of neutropenia was 50.9% (27/53) with 4 cases of FN. In the patients who received major surgery (grade 3-4) or those who did not receive major surgery (grade 1-2 and no surgery), the incidence of neutropenia was 60.0% (36/60) or 34.0% (16/47), respectively; there was significant difference (P < 0.05). In the patients who received radiotherapy or those without radiotherapy, the incidence of neutropenia was 70.0% (14/20) or 43.7% (38/87), respectively; there was significant difference (P < 0.05). Conclusion: The prophylactic use of PEG-rhG-CSF can avoid severe myelotoxicity in the majority of patients with soft tissue sarcoma. However, the risk of neutropenia is still high in the patients who received chemotherapy based on ifosfamide and anthracyclines, as well as in the patients who have received radiotherapy and major surgery in the past. All these are worthy of concern.

Efficacy and safety of PEG-rhG-CSF therapy in the primary and secondary prevention of chemotherapy-induced neutropenia / 中国肿瘤临床

Objective: To evaluate the efficacy and safety of PEG-rhG-CSF therapy in the primary and secondary prevention of chemo-therapy-induced neutropenia . Methods: This single-center, one-arm, and open-label clinical study involved 217 patients with non-my-eloid malignant tumors. These patients included 18 gynecologic oncology (3 endometrial and 15 ovarian cancer), 50 breast cancer, 30 bone tumor, and 119 lymphoma patients who underwent a total of 774 cycles of chemotherapy, comprising 146 primary and 71 sec-ondary prevention patients. The patients ≥45 kg and those <45 kg received a single subcutaneous injection of 6 mg and 3 mg PEG-rhG-CSF, respectively, 24-48 h after the chemotherapy was completed. All patients received only one dose of PEG-rhG-CSF admin-istration per chemotherapy cycle. Results: The overall incidence of febrile neutropenia (FN) was found to be 5.7%, with rates of 4.9% and 7.2% in the primary and secondary prevention groups, respectively. Univariate and multivariate Logistic regression analyses re-vealed that the longer PEG-rhG-CSF was sustained in the treatment cycle, the lower the incidence of FN was. The incidence of FN was significantly lower in the second cycle of the treatment than in the first in both the primary and secondary prevention groups (cycle 1 vs. cycle 2: 11.6% vs. 4.4%, respectively, P=0.039, in the primary group; 16.9% vs. 5.6%, respectively, P=0.034, in the secondary group). The overall incidence of gradeⅣneutropenia was 10.3% (80/774), with rates of 6.7% (34/510) and 17.4% (46/264) in the primary and secondary prevention groups, respectively (P<0.001). The incidence of gradeⅣneutropenia was significantly lower in the second cy-cle of the treatment than in the first (cycle 1 vs. cycle 2: 17.1% vs. 5.3%, respectively, P=0.004, in the primary group; 46.5% vs. 11.3%, respectively, P<0.001, in the secondary group). The treatment-induced toxicity mainly involved bone pain, with 3.7% (8/217) and 1.8% (4/217) incidence rates for grade 1-2 and 3-4 bone pain, respectively. Conclusions: PEG-rhG-CSF administration can effectively reduce the incidence of FN (5.7%) when prophylactically applied to patients with non-myeloid malignant tumors. Primary prevention can sig- nificantly reduce the risk of grade IV neutropenia in all chemotherapy cycles relative to the secondary prevention.