Treatment Of Chemotherapy-induced Febrile Neutropenia Research Articles

Pegfilgrastim-Apgf (Nyvepria): Biosimilar USFDA Approval for the Treatment of Chemotherapy-induced Febrile Neutropenia and Current Updates on Clinical Trials.

Pegfilgrastim-apgf (nyvepria) was currently approved by FDA for the treatment of febrile neutropenia associated with non-myeloid malignancies receiving myelosuppressive anticancer drugs. It was developed by Pfizer, USA. It is a PEGylated leukocyte growth-stimulating factor indicated to reduce the incidence of febrile neutropenia in patients receiving anticancer drugs. Nyvepria is biosimilar to pegfilgrastim, approved by FDA on June 10, 2020. It is the fourth FDA-approved drug for the treatment of infection exhibiting febrile neutropenia. This review abridges the indicators in the development of nyvepria foremost to approval for the treatment of febrile neutropenia (FN), a biosimilar regulatory framework, and current updates on the clinical trials (CTs).

Targeting GGT1 Eliminates the Tumor-Promoting Effect and Enhanced Immunosuppressive Function of Myeloid-Derived Suppressor Cells Caused by G-CSF.

Myeloid-derived suppressor cells (MDSCs) are major immunosuppressive cells that accumulate in tumor-bearing hosts. Since MDSCs suppress anti-tumor immunity and promote tumor progression, they are promising targets for cancer immunotherapy. Granulocyte colony-stimulating factor (G-CSF) is an agent used for the treatment of chemotherapy-induced febrile neutropenia (FN) in patients with cancer. However, several reports have revealed that G-CSF plays crucial immune-related adverse roles in tumor progression through MDSCs. In this study, we showed that MDSCs differentiated in the presence of G-CSF in vitro exhibited enhanced proliferation and immunosuppressive activity compared to those differentiated without G-CSF. RNA sequencing analysis demonstrated that G-CSF enhanced the immunosuppressive function of MDSCs by upregulating gamma-glutamyltransferase (GGT) 1. Moreover, in the EL4 lymphoma-bearing neutropenic mouse model, administration of recombinant G-CSF increased the number of MDSCs and attenuated the anti-cancer effect of chemotherapy. We showed that the combination of GGsTop, a GGT inhibitor, could prevent G-CSF-induced tumor growth, without affecting the promotion of myelopoiesis by G-CSF. These results suggest that targeting GGT1 can mitigate G-CSF-induced enhanced immunosuppressive functions of MDSCs and can eliminate the tumor-promoting effect of G-CSF. Furthermore, GGsTop could be an attractive combination agent during G-CSF treatment for FN in patients with cancer.

Budget Saving Potential of Pegfilgrastim Biosimilar for the Treatment of Chemotherapy-Induced Febrile Neutropenia, in Italy

INTRODUCTION: Current Italian guidelines recommend prophylaxis with granulocyte colony-stimulating factors (G-CSFs) to reduce the risk of chemotherapy-induced febrile neutropenia (FN). The availability of G-CSF biosimilars represents an opportunity for savings in the Italian National Healthcare Service (NHS) delivery of care.OBJECTIVE: To assess the cost saving potential associated with the introduction of pegfilgrastim biosimilars to local formularies, compared to the current G-CSF standard practice in Italy.METHODS: A budget impact model was developed to compare the current standard practice of long-acting (LA) and short-acting (SA) G-CSFs use, with a future scenario in which the market share of LA G-CSFs grows due to the more advantageous administration schedule and price of pegfilgrastim biosimilar. The analysis included G-CSF treatment schedules, drug acquisition costs and costs of patient management including hospitalization and ambulatory care.RESULTS: The introduction of pegfilgrastim biosimilar resulted in cumulative 3-year cost savings of € 59,650 and € 41,539 for FN prophylaxis in a potential cohort of 1000 patients with solid tumors and lymphomas, respectively.CONCLUSIONS: The results indicate that the introduction of pegfilgrastim biosimilar is potentially associated with substantial cost savings for the Italian healthcare system.

Colony-stimulating factors for chemotherapy-induced febrile neutropenia.

Febrile neutropenia is a frequent adverse event experienced by people with cancer who are undergoing chemotherapy, and is a potentially life-threatening situation. The current treatment is supportive care plus antibiotics. Colony-stimulating factors (CSFs), such as granulocyte-CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF), are cytokines that stimulate and accelerate the production of one or more cell lines in the bone marrow. Clinical trials have addressed the question of whether the addition of a CSF to antibiotics could improve outcomes in individuals diagnosed with febrile neutropenia. However, the results of these trials are conflicting. To evaluate the safety and efficacy of adding G-CSF or GM-CSF to standard treatment (antibiotics) when treating chemotherapy-induced febrile neutropenia in individuals diagnosed with cancer. We conducted the search in March 2014 and covered the major electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and SCI. We contacted experts in hematology and oncology and also scanned the citations from the relevant articles. We searched for randomized controlled trials (RCTs) that compared CSF plus antibiotics versus antibiotics alone for the treatment of chemotherapy-induced febrile neutropenia in adults and children. We used the standard methodological procedures expected by The Cochrane Collaboration. We performed meta-analysis of the selected studies using Review Manager 5 software. Fourteen RCTs (15 comparisons) including a total of 1553 participants addressing the role of CSF plus antibiotics in febrile neutropenia were included. Overall mortality was not improved by the use of CSF plus antibiotics versus antibiotics alone (hazard ratio (HR) 0.74 (95% confidence interval (CI) 0.47 to 1.16) P = 0.19; 13 RCTs; 1335 participants; low quality evidence). A similar finding was seen for infection-related mortality (HR 0.75 (95% CI 0.47 to 1.20) P = 0.23; 10 RCTs; 897 participants; low quality evidence). Individuals who received CSF plus antibiotics were less likely to be hospitalized for more than 10 days (risk ratio (RR) 0.65 (95% CI 0.44 to 0.95) P = 0.03; 8 RCTs; 1221 participants; low quality evidence) and had more number of participants with a more faster neutrophil recovery (RR 0.52 (95% CI 0.34 to 0.81) P = 0.004; 5 RCTs; 794 participants; moderate quality evidence) than those treated with antibiotics alone. Similarly, participants receiving CSF plus antibiotics had shorter duration of neutropenia (standardized mean difference (SMD) -1.70 (95% CI -2.65 to -0.76) P = 0.0004; 9 RCTs; 1135 participants; moderate quality evidence), faster recovery from fever (SMD -0.49 (95% CI -0.90 to -0.09) P value = 0.02; 9 RCTs; 966 participants; moderate quality evidence) and shorter duration of antibiotics use (SMD -1.50 (95% CI -2.83 to -0.18) P = 0.03; 3 RCTs; 457 participants; low quality evidence) compared with participants receiving antibiotics alone. We found no significant difference in the incidence of deep venous thromboembolism (RR 1.68 (95% CI 0.72 to 3.93) P = 0.23; 4 RCTs; 389 participants; low quality evidence) in individuals treated with CSF plus antibiotics compared with those treated with antibiotics alone. We found higher incidence of bone or joint pain or flu-like symptoms (RR 1.59 (95% CI 1.04 to 2.42) P = 0.03; 6 RCTs; 622 participants; low quality evidence) in individuals treated with CSF plus antibiotics compared with those treated with antibiotics alone. Overall, the methodological quality of studies was moderate to low across different outcomes. The main reasons to downgrade the quality of evidence were inconsistency across the included studies and imprecision of results. The use of a CSF plus antibiotics in individuals with chemotherapy-induced febrile neutropenia had no effect on overall mortality, but reduced the amount of time participants spent in hospital and improved their ability to achieve neutrophil recovery. It was not clear whether CSF plus antibiotics had an effect on infection-related mortality. Participants receiving CSFs had shorter duration of neutropenia, faster recovery from fever and shorter duration of antibiotics use.

Single-Agent, Broad-Spectrum Fluoroquinolones for the Outpatient Treatment of Low-Risk Febrile Neutropenia

To evaluate the use of oral, single-agent, broad-spectrum fluoroquinolones in the treatment of low-risk febrile neutropenia (FN). MEDLINE via Ovid (1948 to May, week 3, 2011) and EMBASE (1980 to 2011, week 21) were searched using the terms febrile neutropenia, fluoroquinolone, quinolone derivative, levofloxacin, moxifloxacin, and neoplasm. References of selected articles, review articles, and treatment guidelines were reviewed. Trials evaluating the efficacy of oral, single-agent, broad-spectrum fluoroquinolones in the treatment of chemotherapy-induced FN were included if the majority of patients in the study had low-risk FN. Trials involving pediatric patients, non-Food and Drug Administration-approved fluoroquinolones, or monotherapy with ciprofloxacin or ofloxacin were excluded. Data extracted included study design, patient demographics, antiinfective regimens, and treatment outcomes. Four clinical trials were included. One trial compared levofloxacin with piperacillin/tazobactam with a success rate (afebrile at 72 hours) of 76.5% in the levofloxacin group compared with 88.3% in the piperacillin/tazobactam group. This trial was not limited to low-risk patients. The remaining 3 trials investigated moxifloxacin monotherapy in low-risk patients. Two of these were noncontrolled trials with success rates (afebrile at 5 days) of 91% and 95%. The final trial randomized patients to moxifloxacin or ceftriaxone and had success rates (hospital discharge at 48 hours) of 79.2% and 73.9%, respectively. In all 4 trials, treatment of FN with levofloxacin or moxifloxacin was deemed to be safe and effective. Although all studies had positive results, they were limited by small sample sizes and the absence of universal use of control comparisons. Use of oral, single-agent, broad-spectrum fluoroquinolones for outpatient treatment of FN in low-risk patients has shown promising results. At this time, this type of therapy should be limited to low-risk patients. Future clinical trials should include larger sample sizes and a comparison with existing first-line oral therapy-oral ciprofloxacin plus amoxicillin/clavulanate.

Economic evaluations of granulocyte colony-stimulating factor: in the prevention and treatment of chemotherapy-induced neutropenia.

The prevailing uncertainty about the pharmacoeconomic positioning of granulocyte colony-stimulating factor (G-CSF) in the prevention and treatment of chemotherapy-induced febrile neutropenia has resulted in a number of pharmacoeconomic evaluations published in the past 10 years. These studies vary considerably regarding the approaches used and the results presented. In order to contribute to a clearer pharmacoeconomic positioning of G-CSF, a systematic review of economic evaluations was carried out. The focus of the review was prophylaxis and therapy of chemotherapy-induced neutropenia in patients with cancer. A computerised bibliography search of several databases was conducted yielding 33 studies. The findings demonstrated the cost-saving potential of G-CSF in standard-dose chemotherapy to be limited, with lower costs often seen in the control group. The results of these studies were too heterogeneous to extract a clear recommendation from a cost-saving point of view. The administration of G-CSF after high-dose chemotherapy with stem cell support resulted more often in cost savings in the G-CSF group as compared with standard-dose chemotherapy, illustrating a possible cost-saving potential of G-CSF. In the treatment of established chemotherapy-induced febrile neutropenia, cost savings were found in all studies. This result is surprising but hampered by the small number of studies (n = 5) and remains to be confirmed by more rigourously designed prospective economic analyses. Despite the substantial research on this topic, the economic evaluation of G-CSF is far from being settled and needs further investigation.

Economic Comparison of Home-Care-Based versus Hospital-Based Treatment of Chemotherapy-Induced Febrile Neutropenia in Children

Objective The purpose of this study was to compare health-care resource utilization and outcomes among children treated for low-risk febrile neutropenia (FN) in a hospital-based setting with those treated in a home-care-based setting. Methods The perspective of this retrospective, cohort study was the health payer. We collected health-care utilization and treatment outcome data from medical records of 63 children (26 boys and 37 girls) with low-risk, chemotherapy-induced FN who were treated at the University of Arizona (27 children, the hospital-based group) and University of New Mexico (36 children, the home-care-based group). We identified 144 FN episodes (72 episodes in each group). Health-care utilization included physician visits, home-care visits, laboratory visits, outpatient visits, hospital days, intensive care unit days, medical tests and studies, and medications used to manage FN (e.g., filgrastim, antimicrobials, and ancilliary drugs and supplies). We applied uniform charges, based on those used at the University of New Mexico in 1998. We collected outcomes of the FN treatment (success vs. failure and time to resolution, defined as number of days of antibiotic therapy). Rates of positive blood cultures during treatment were also compared. Data were analyzed using nonparametric Mann–Whitney U tests for continuous data and chi-square analysis for categorical data. Sensitivity analyses were conducted by varying the amount of total resource utilization, as well as utilization of specific health-care resources. Results There was no difference in outcome; all episodes of treatment in both groups resulted in successful recovery from FN. Time to resolution of FN was 8.3 ± 2.7 days for home-care FN episodes versus 7.3 ± 3.6 days for hospital FN episodes ( P =.064). Median charge per FN episode was significantly ( P< .001) greater when managed in the hospital compared to home care ($9392 vs. $5893). There was greater use of laboratory and radiographic studies in the hospital-based patients ( P < .01). However, children in the home-care-based group were more often treated with granulocyte colony-stimulating factor (filgrastim, median charge $1085 vs. $451, P < .001), and median antibiotic charges were higher ($2523 vs. $1526, P < .001). Positive blood cultures were more common among the hospital-based FN treatments (30.6 vs. 11.1%, P=.012). Conclusions We found that management of low-risk FN in a home-care-based setting was associated with significantly lower median total charges with no differences in outcome.