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Pain Management Nursing : Official... Apr 2024Breast cancer patients on chemotherapy who receive pegfilgrastim to prevent neutropenia may experience severe bone pain as a side effect. Traditional treatment...
AIMS
Breast cancer patients on chemotherapy who receive pegfilgrastim to prevent neutropenia may experience severe bone pain as a side effect. Traditional treatment recommendations include nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, opioids, and/or antihistamine use. However, little research was found comparing these interventions. The study aim was to address the gaps in literature and to explore the use of and perceived effectiveness of loratadine versus acetaminophen or NSAIDs in women with breast cancer treated with pegfilgrastim. This study also sought to understand how patients became aware of loratadine or other treatments for management of bone pain.
DESIGN/METHODS
This cross-sectional study used survey methods to collect data from 66 adult female breast cancer patients receiving chemotherapy with pegfilgrastim.
RESULTS
The incidence of bone pain was 45% (n = 30) in our sample, but more than half (n = 45; 69%) of the women took either acetaminophen, NSAIDs, or loratadine alone or in combination to prevent bone pain. All medication were rated as effective by patients, with acetaminophen slightly more effective than loratadine, and loratadine more effective than NSAIDs.
CONCLUSIONS
Acetaminophen, NSAIDs, and loratadine are easily available and inexpensive. However, unlike acetaminophen and NSAIDs, loratadine is dosed once a day and well tolerated with minimal adverse effects.
CLINICAL IMPLICATIONS
Randomized controlled trials are needed to adequately assess the effectiveness of all three medication options. Because little is known about optimal use of any of these medications for pegfilgrastim-induced bone pain, it is also important to identify the optimal time to initiate treatment and ideal treatment duration.
Topics: Adult; Female; Humans; Loratadine; Acetaminophen; Cross-Sectional Studies; Bone Diseases; Musculoskeletal Pain; Breast Neoplasms; Anti-Inflammatory Agents, Non-Steroidal; Filgrastim; Polyethylene Glycols
PubMed: 38216368
DOI: 10.1016/j.pmn.2023.12.004 -
Supportive Care in Cancer : Official... Jan 2024Evaluate the safety and efficacy of efbemalenograstim alfa for neutrophil support in breast cancer patients undergoing myelosuppressive chemotherapy in a phase 2,... (Randomized Controlled Trial)
Randomized Controlled Trial
Efbemalenograstim alfa not inferior to pegfilgrastim in providing neutrophil support in women with breast cancer undergoing myelotoxic chemotherapy: results of a phase 2 randomized, multicenter, open-label trial.
PURPOSE
Evaluate the safety and efficacy of efbemalenograstim alfa for neutrophil support in breast cancer patients undergoing myelosuppressive chemotherapy in a phase 2, dose-finding, open-label study (NCT01648322, ClinicalTrials.gov, 2012-07-19).
METHODS
232 patients received up to 4 cycles of chemotherapy, 141 patients with docetaxel + cyclophosphamide (TC) and 91 patients with docetaxel + doxorubicin + cyclophosphamide (TAC). Patients were randomized to efbemalenograstim alfa (80, 240, or 320 µg/kg [TC]; 240 or 320 µg/kg [TAC]) or pegfilgrastim (6 mg) on Day 2 of each cycle.
RESULTS
Efbemalenograstim alfa was non-inferior to pegfilgrastim in duration of moderate and severe neutropenia (absolute neutrophil count [ANC] < 1.0 × 10/L) in TAC Cycle 1 (mean [SD] of 2.1 [1.58] and 2.1 [1.46] days for 240 µg/kg and 320 µg/kg efbemalenograstim alfa, respectively, and 1.8 [1.28] days for pegfilgrastim), with a difference (95% CI) of 0.3 (-0.4, 1.1) days. ANC nadir occurred between Days 7-8 of TAC Cycle 1, with mean [SD] of 0.68 [1.064], 0.86 [1.407] and 0.78[1.283] × 10/L for 240 µg/kg, 320 µg/kg efbemalenograstim alfa and pegfilgrastim, respectively. Time to ANC recovery post nadir (defined as an ANC > 2.0 × 10/L after the expected ANC nadir) was 2.0-2.4 and 1.9 days for TAC patients treated with efbemalenograstim alfa and pegfilgrastim, respectively. No significant difference was found between any dose of efbemalenograstim alfa and pegfilgrastim in TAC Cycle 1 for incidence of moderate to severe neutropenia (76%-77% of patients) or incidence of severe neutropenia (ANC < 0.5 × 10/L; 63%-72%). Efbemalenograstim alfa exhibited similar safety profile to pegfilgrastim. Febrile neutropenia occurred in 4 (1.8%) patients, 2 patients each for 320 µg/kg efbemalenograstim alfa and pegfilgrastim, with no event considered related to study drug.
CONCLUSION
Efbemalenograstim alfa was comparable to pegfilgrastim in efficacy and safety.
GOV IDENTIFIER
NCT01648322.
Topics: Humans; Female; Neutrophils; Breast Neoplasms; Docetaxel; Neutropenia; Cyclophosphamide
PubMed: 38194162
DOI: 10.1007/s00520-023-08260-x -
Annals of Hematology Mar 2024Data about biosimilar Peg-filgrastim (bioPEG) in autologous stem cell transplant (ASCT) are still scarce. The aim of this study has been to assess efficacy and safety of...
Efficacy and safety of biosimilar Peg-filgrastim after autologous stem cell transplant in myeloma and lymphoma patients: a comparative study with biosimilar Filgrastim, Lenograstim, and originator Peg-filgrastim.
Data about biosimilar Peg-filgrastim (bioPEG) in autologous stem cell transplant (ASCT) are still scarce. The aim of this study has been to assess efficacy and safety of bioPEG among lymphoma and myeloma patients undergoing ASCT, comparing these data with historical controls receiving other G-CSFs. Furthermore, an economic evaluation has been included to estimate the savings by using bioPEG. This is a prospective cohort study comparing lymphoma and myeloma patients undergoing ASCT and receiving bioPEG (n = 73) with three historical consecutive cohorts collected retrospectively who received other G-CSFs (Lenograstim - Leno - n = 101, biosimilar Filgrastim - bioFIL n = 392, and originator Peg-filgrastim - oriPEG n = 60). We observed a significantly shorter time to neutrophils and platelet engraftment (p < 0.001) in patients treated with bioPEG and oriPEG. Moreover, patients who received bioPEG showed a shorter hospitalization time (p < 0.001) and a lower transfusion need (p < 0.001). We did not observe any significant difference in terms of transplant-related mortality, mucositis, and diarrhea among the four groups. No serious adverse events were associated with bioPEG. Similar data were obtained after running a stratified analysis for lymphomas and myeloma separately conducted by using a propensity score matching. The average total cost per patient of bioPEG was € 18218.9 compared to € 23707.8, € 20677.3 and € 19754.9 of Leno, oriPEG, and bioFIL, respectively. In conclusion, bioPEG seems to be as effective as the originator and more effective than short-acting G-CSFs in terms of post-transplant engraftment in myeloma and lymphoma patients undergoing ASCT. Moreover, bioPEG was cost-effective when compared with the other G-CSFs.
Topics: Humans; Filgrastim; Lenograstim; Multiple Myeloma; Biosimilar Pharmaceuticals; Retrospective Studies; Prospective Studies; Lymphoma; Granulocyte Colony-Stimulating Factor; Stem Cell Transplantation; Recombinant Proteins; Hematopoietic Stem Cell Mobilization
PubMed: 38189833
DOI: 10.1007/s00277-023-05604-9 -
Advances in Therapy Mar 2024To help prevent febrile neutropenia, pegfilgrastim-cbqv (UDENYCA; Coherus BioSciences), a pegfilgrastim (NEULASTA; Amgen) biosimilar, is administered 24-96 h after... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
To help prevent febrile neutropenia, pegfilgrastim-cbqv (UDENYCA; Coherus BioSciences), a pegfilgrastim (NEULASTA; Amgen) biosimilar, is administered 24-96 h after myelosuppressive chemotherapy. Delivery of pegfilgrastim-cbqv using an on-body injector (OBI) provides an alternative method of administration, affording options in drug delivery. This study aimed to establish pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence and assess the safety of pegfilgrastim-cbqv administered using an OBI compared with a prefilled syringe (PFS).
METHODS
In this open-label, two-period crossover study, healthy adult male participants (N = 189) were randomly assigned 1:1 to receive pegfilgrastim-cbqv 6 mg subcutaneously using an OBI (n = 92) or a PFS (n = 95) in period 1 and then an injection via the other method in period 2. Primary PK end points were area under the concentration-time curve from time 0 to infinity, area under the concentration-time curve from time 0 to the last quantifiable concentration, and maximum plasma concentration. Secondary PD end points, safety, immunogenicity, and tolerability were also assessed.
RESULTS
The 90% confidence intervals (CIs) of the geometric mean ratios for the PK and PD end points fell within the predetermined range (80-125%), indicating PK and PD bioequivalence between pegfilgrastim-cbqv OBI and pegfilgrastim-cbqv PFS. Treatment-emergent adverse events (TEAEs) occurred in 87.8% and 75.8% of participants in the OBI and PFS groups, respectively. Most TEAEs were musculoskeletal effects. The most common OBI-related TEAE was injection site erythema (31.7%), which was mild, transient, and self-limiting. The incidence of treatment-emergent antidrug antibodies (ADAs) was similar between the OBI and PFS. ADAs had no apparent impact on PK, PD, or safety. Neutralizing antibodies were not detected in any participant.
CONCLUSIONS
Results of the study showed PK and PD bioequivalence of pegfilgrastim-cbqv administered using OBI compared with PFS. OBI and PFS administration had similar safety, tolerability, and immunogenicity profiles. No unexpected safety signals were identified. Graphical Abstract available for this article.
Topics: Adult; Humans; Male; Therapeutic Equivalency; Cross-Over Studies; Syringes; Filgrastim; Polyethylene Glycols; Healthy Volunteers; Biosimilar Pharmaceuticals
PubMed: 38180721
DOI: 10.1007/s12325-023-02735-3 -
European Journal of Pharmaceutics and... Jan 2024We herein report that filgrastim product Neupogen® and the filgrastim formulation buffer induced aggregate formation when mixed in vitro with human plasma, and...
We herein report that filgrastim product Neupogen® and the filgrastim formulation buffer induced aggregate formation when mixed in vitro with human plasma, and formation of large membranous erythrocyte aggregates when mixed with human blood, similar to the aggregation induced by pegfilgrastim and by pegfilgrastim buffer [T. Arvinte, E. Poirier, N. Ersayin, G. Darpin, A. Cudd, J. Dowd, S. Brokx, Aggregation of human plasma and of human blood induced in vitro by pegfilgrastim originator formulation buffer and pegfilgrastim products, Eur. J. Pharmaceut. Biopharmaceut. (2023), doi: 10.1016/j.ejpb.2023.10.019]. The data identify the filgrastim buffer (which is practically the same in filgrastim and pegfilgrastim products) as the main driver of human plasma and blood aggregation. Kinetic experiments showed differences in the extent of plasma aggregation induced by a filgrastim product manufactured in EU and one manufactured in USA. Human donor variability in the plasma aggregation induced by filgrastim was observed. To study the effect of PEGylation of the filgrastim protein on plasma aggregation we compared filgrastim (Neupogen®) with pegfilgrastim (Neulasta®) solutions at the same protein concentration. These data show that PEGylation has a beneficial effect in inhibiting to an extent plasma aggregation. Interestingly, 20 kDa polyethylene glycol in the filgrastim buffer induced more plasma aggregation compared to the buffer, similar to the aggregation induced by pegfilgrastim. For intravenous infusion filgrastim solutions (300 µg/ml, vials only) may be diluted in 5 % dextrose from a concentration of 300 µg/ml to 5 µg/ml. Aggregation of human plasma was also induced by filgrastim solutions diluted in 5 % dextrose to 50 µg/ml, 15 µg/ml and 5 µg/ml filgrastim, as well as by the filgrastim buffer similarly diluted in 5 % dextrose (1:6, 1:20 and 1:60 dilution). These data show that filgrastim solutions used for intravenous administration in patients induce human plasma aggregation in vitro. Such aggregation phenomena may be related to known infusion side effects of filgrastim therapy.
Topics: Humans; Filgrastim; Granulocyte Colony-Stimulating Factor; Injections; Polyethylene Glycols; Glucose; Recombinant Proteins
PubMed: 38097022
DOI: 10.1016/j.ejpb.2023.12.004 -
International Journal of Clinical... Feb 2024Neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy is a new standard for locally advanced esophageal squamous cell carcinoma. The optimal timing of...
BACKGROUND
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.
METHODS
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.
RESULTS
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 7 days 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.
CONCLUSION
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.
Topics: Humans; Cisplatin; Docetaxel; Esophageal Neoplasms; Fluorouracil; Neoadjuvant Therapy; Retrospective Studies; Esophageal Squamous Cell Carcinoma; Antineoplastic Combined Chemotherapy Protocols; Neutropenia; Filgrastim; Polyethylene Glycols
PubMed: 38063978
DOI: 10.1007/s10147-023-02438-3 -
EClinicalMedicine Dec 2023Immune checkpoint inhibitors (ICI) plus platinum-based chemotherapy has been recognized as a standard first-line therapy in non-small cell lung cancer (NSCLC); however,...
Efficacy and safety of second-line therapy of docetaxel plus ramucirumab after first-line platinum-based chemotherapy plus immune checkpoint inhibitors in non-small cell lung cancer (SCORPION): a multicenter, open-label, single-arm, phase 2 trial.
BACKGROUND
Immune checkpoint inhibitors (ICI) plus platinum-based chemotherapy has been recognized as a standard first-line therapy in non-small cell lung cancer (NSCLC); however, no prospective clinical trials of docetaxel (DTX) plus ramucirumab (RAM) following first-line ICI plus platinum-based chemotherapy has been reported.
METHODS
In this multicentre, open-label, single-arm, phase 2 trial, we enrolled patients with NSCLC from eight centres in Japan. Patients with metastatic NSCLC with disease progression after platinum-based chemotherapy plus ICI were eligible for the study. Patients were intravenously treated with 60 mg/m of DTX and 10 mg/kg of RAM on day 1 with a strong recommendation of pegfilgrastim administration on day 2 every 3 weeks. The primary end point was objective response rate (ORR) in efficacy analysis population. Safety was assessed in all patients treated at least one dose. The ORR of the null and alternative hypotheses were 10% and 30%, with α error of 0.1 and β error of 0.1. This trial is registered with the Japan Registry for Clinical Trials, jCRTs041190077.
FINDINGS
Between 16 January, 2020, and 24 August, 2021, 33 patients (median age 66 [range 42-79] years) were enrolled. Thirteen patients (41%) had Eastern Cooperative Oncology Group performance status of 1. Twenty-five patients (78%) had an interval of <60 days after the last administration of ICI. In the efficacy analysis population (n = 32), the primary endpoint was met as 11 patients achieved partial response (PR), with ORR of 34.4% (80% CI, 23.1-47.2). Grade ≥3 anaemia and febrile neutropenia were observed in 2 (6%) and 3 (9%) patients, respectively. No treatment-related deaths and no new safety signals were observed.
INTERPRETATION
DTX plus RAM demonstrated encouraging antitumor activity with a manageable safety profile in patients who have progressed on front-line ICIs plus platinum-based chemotherapy. The results of this trial can be a helpful reference in conducting further phase III trials of new second-line treatment options.
FUNDING
Eli Lilly Japan K.K.
PubMed: 38034077
DOI: 10.1016/j.eclinm.2023.102303 -
Case Reports in Oncology 2023Granulocyte colony-stimulating factor (G-CSF), including pegfilgrastim, increases the peripheral blood leukocyte count and is widely used in clinical practice in...
INTRODUCTION
Granulocyte colony-stimulating factor (G-CSF), including pegfilgrastim, increases the peripheral blood leukocyte count and is widely used in clinical practice in combination with cytotoxic chemotherapy. The most frequent side effects of G-CSF are pain and fever; aortitis, in contrast, is a rare and serious side effect.
CASE PRESENTATION
A 73-year-old man with small-cell lung cancer was treated with a full dose of a combination of carboplatin/etoposide/durvalumab and pegfilgrastim. The patient developed fever and right ear pain 12 days after pegfilgrastim administration and was diagnosed with aortitis by contrast-enhanced computed tomography 5 days later. Because the patient had already been administered the immune checkpoint inhibitor and had a history of hepatitis B, the patient was followed up without corticosteroid administration, and the patient's symptoms resolved spontaneously.
CONCLUSION
In situations where immunosuppression should be avoided, we believe that follow-up without corticosteroids for G-CSF-induced aortitis is a promising option.
PubMed: 38028576
DOI: 10.1159/000534931 -
Cureus Oct 2023Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune pathologies often associated with occult malignancies. Glucocorticoids (GCs)...
Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune pathologies often associated with occult malignancies. Glucocorticoids (GCs) represent the initial therapy to control symptoms and avoid complications. Immune checkpoint inhibitors (ICIs) have shifted the paradigm of cancer treatment. Nivolumab has become the first-line therapy in combination with chemotherapy for untreated, unresectable, non-HER-2-positive advanced gastroesophageal adenocarcinoma. The use of ICIs increases the risk of immune-related adverse events (irAEs), especially in patients with autoimmune diseases, and patients receiving steroids or immunosuppressants might be associated with poorer immunotherapy efficacy. We describe the case of a 49-year-old male who was diagnosed with paraneoplastic dermatomyositis (PDM) and gastroesophageal adenocarcinoma. He was started on prednisone taper, and concomitantly, he was started on chemotherapy with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT), with administration of pegfilgrastim and dexamethasone during each cycle. Additionally, he was started on nivolumab. His course was complicated by worsening episodes of myopathies due to the immunotherapy, requiring adjustments to the prednisone taper. A positron emission tomography (PET) scan and repeat endoscopic ultrasonography with biopsy eight months after therapy initiation showed no major evidence of disease compared to prior. In our case, we exemplified the importance of multidisciplinary management for dosing and tapering of GCs and timing of ICI initiation, and we described the successful response to nivolumab in a patient with autoimmune disease concurrently receiving GCs.
PubMed: 38021941
DOI: 10.7759/cureus.47628 -
Transplantation Apr 2024Pegfilgrastim, a long-acting form of granulocyte-colony stimulating factor, with a convenient single-injection dosage, is being investigated for peripheral blood stem...
BACKGROUND
Pegfilgrastim, a long-acting form of granulocyte-colony stimulating factor, with a convenient single-injection dosage, is being investigated for peripheral blood stem cell (PBSC) mobilization in healthy volunteers. However, data on the adequate dose of pegfilgrastim for PBSC mobilization are limited. This phase 2, single-arm study evaluated the efficacy and safety of pegfilgrastim for PBSC mobilization in healthy volunteers.
METHODS
The study comprised 2 phases: pilot (steps 1-3, dose escalation, a single subcutaneous dose of 3.6, 7.2, and 10.8 mg pegfilgrastim, respectively) and evaluation (step 4, efficacy and safety assessments). The primary endpoint was the proportion of subjects who achieved mobilization of ≥20 × 10 6 /L cluster of differentiation 34 positive (CD34 + ) cells.
RESULTS
Thirty-five subjects (6 each in steps 1 and 2 and 23 in step 4) were included. In the pilot phase, step 3 with a 10.8 mg dose was not conducted due to favorable outcomes in step 2 (desired CD34 + cell count), at 7.2 mg pegfilgrastim, which was identified as the optimal dose for the evaluation phase. In the evaluation phase, successful CD34 + mobilization was achieved in all 23 subjects. The mean peripheral blood CD34 + cells count peaked on day 5. Back pain, thrombocytopenia, transient elevations of alkaline phosphatase, and lactate dehydrogenase were the most common adverse events. All adverse events were mild, and none led to study discontinuation.
CONCLUSIONS
A single-dose pegfilgrastim successfully mobilized an optimal number of CD34 + cells and was well tolerated. Pegfilgrastim could be an alternative option for PBSC mobilization in healthy volunteers. The trial was registered at www.clinicaltrials.gov (NCT03993639).
Topics: Humans; Hematopoietic Stem Cell Mobilization; Filgrastim; Granulocyte Colony-Stimulating Factor; Polyethylene Glycols; Antigens, CD34; Recombinant Proteins
PubMed: 38012835
DOI: 10.1097/TP.0000000000004880