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Journal of Clinical Oncology : Official... Nov 2020Limitations of the paclitaxel-doxorubicin-cisplatin (TAP) regimen in the treatment of endometrial cancer include tolerability and cumbersome scheduling. The Gynecologic... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Limitations of the paclitaxel-doxorubicin-cisplatin (TAP) regimen in the treatment of endometrial cancer include tolerability and cumbersome scheduling. The Gynecologic Oncology Group studied carboplatin plus paclitaxel (TC) as a noninferior alternative to TAP.
METHODS
GOG0209 was a phase III, randomized, noninferiority, open-label trial. Inclusion criteria were stage III, stage IV, and recurrent endometrial cancers; performance status 0-2; and adequate renal, hepatic, and marrow function. Prior radiotherapy and/or hormonal therapy were permitted, but chemotherapy, including radiosensitization, was not. Patients were treated with doxorubicin 45 mg/m and cisplatin 50 mg/m (day 1), followed by paclitaxel 160 mg/m (day 2) with granulocyte colony-stimulating factor or paclitaxel 175 mg/m and carboplatin area under the curve 6 (day 1) every 21 days for seven cycles. The primary endpoint was overall survival (OS; modified intention to treat). Progression-free survival (PFS), health-related quality of life (HRQoL), and toxicity were secondary endpoints.
RESULTS
From 2003 to 2009, 1,381 women were enrolled. Noninferiority of TC to TAP was concluded for OS (median, 37 41 months, respectively; hazard ratio [HR], 1.002; 90% CI, 0.9 to 1.12), and PFS (median, 13 14 months; HR, 1.032; 90% CI, 0.93 to 1.15). Neutropenic fever was reported in 7% of patients receiving TAP and 6% of those receiving TC. Grade > 2 sensory neuropathy was recorded in 26% of patients receiving TAP and 20% receiving TC ( = .40). More grade ≥ 3 thrombocytopenia (23% 12%), vomiting (7% 4%), diarrhea (6% 2%), and metabolic (14% 8%) toxicities were reported with TAP. Neutropenia (52% 80%) was more common with TC. Small HRQoL differences favored TC.
CONCLUSION
With demonstrated noninferiority to TAP, TC is the global first-line standard for advanced endometrial cancer.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cisplatin; Endometrial Neoplasms; Female; Filgrastim; Humans; Middle Aged; Paclitaxel; Progression-Free Survival; Quality of Life; Treatment Outcome
PubMed: 33078978
DOI: 10.1200/JCO.20.01076 -
Supportive Care in Cancer : Official... Jan 2018Filgrastim (NEUPOGEN) is the originator recombinant human granulocyte colony-stimulating factor widely used for preventing neutropenia-related infections and mobilizing... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Filgrastim (NEUPOGEN) is the originator recombinant human granulocyte colony-stimulating factor widely used for preventing neutropenia-related infections and mobilizing hematopoietic stem cells. This report presents findings of a systematic literature review and meta-analysis of efficacy and safety of originator filgrastim to update previous reports.
METHODS
A literature search of electronic databases, congress abstracts, and bibliographies of recent reviews was conducted to identify English-language reports of clinical trials and observational studies evaluating filgrastim in its US-approved indications up to February 2015. Two independent reviewers assessed titles/abstracts and full texts of publications, and extracted data from studies that compared originator filgrastim vs placebo or no treatment. For outcomes with sufficient homogeneous data reported across studies, meta-analysis was performed and relative risk (RR) determined. Data were summarized descriptively for all other evaluated outcomes.
RESULTS
A total of 1194 unique articles evaluating originator filgrastim were identified, with 25 meeting eligibility criteria for data extraction: 18 randomized controlled trials, 2 nonrandomized clinical trials, and 5 observational studies. In chemotherapy-induced neutropenia (CIN), filgrastim vs placebo or no treatment significantly reduced febrile neutropenia incidence (RR 0.63, 95% CI 0.53-0.75) and grade 3 or 4 neutropenia incidence (RR 0.50, 95% CI 0.37-0.68). The most commonly reported adverse event (AE) with filgrastim was bone pain (RR 2.61, 95% CI 1.29-5.27 in CIN). Additional efficacy and safety outcomes are described within indications.
CONCLUSIONS
This systematic literature review and meta-analysis confirms and updates previous reports on the efficacy and safety of originator filgrastim. Bone pain was the commonly reported AE associated with filgrastim use.
Topics: Filgrastim; Granulocyte Colony-Stimulating Factor; Hematologic Agents; Humans
PubMed: 28939926
DOI: 10.1007/s00520-017-3854-x -
Journal of Tissue Engineering and... May 2022Segmental recanalization of chronically occluded arteries was observed in patients with chronic limb-threatening ischemia (CLTI) treated with Filgrastim, a granulocyte...
Segmental recanalization of chronically occluded arteries was observed in patients with chronic limb-threatening ischemia (CLTI) treated with Filgrastim, a granulocyte colony stimulating factor, every 72 h for up to a month, and an infra-geniculate programmed compression pump (PCP) for 3 h daily. Molecular evidence for fibrinolysis and neovascularization was sought. CLTI patients were treated with PCP alone (N = 19), or with Filgrastim and PCP (N = 8 and N = 6, at two institutions). Enzyme-Linked Immunosorbent Assay was used to measure the plasma concentration of plasmin and of fibrin degradation products (FDP), and the serum concentration of proteins associated with neovascularization. In the PCP-alone group, blood was sampled on Day 1 (baseline) and after 30 days of daily PCP. In the Filgrastim and PCP group, blood was drawn on Day 1, and 1 day after the 5th and the 10th Filgrastim doses. Each blood draw occurred before and after 2 h of supervised PCP. Significant (p < 0.01) PCP independent increases in the plasma concentration of plasmin (>10-fold) and FDP (>5-fold) were observed 1 day after both the 5th and the 10th Filgrastim doses, compared to Day 1. Significant (p < 0.05) increases in the concentration of pro-angiogenic proteins (e.g., HGF, MMP-9, VEGF A) were also observed. Filgrastim at this novel dosimetry induced fibrinolysis without causing acute hemorrhage, in addition to inducing a pro-angiogenic milieu conducive to NV. Further clinical testing is warranted at this novel dosimetry in CLTI, as well as in other chronically ischemic tissue beds. Trial registration. https://clinicaltrials.gov/ct2/show/NCT02802852.
Topics: Blood Group Antigens; Fibrinolysin; Fibrinolysis; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Neovascularization, Pathologic; Recombinant Proteins
PubMed: 35175691
DOI: 10.1002/term.3284 -
BMJ Case Reports Jun 2020Drug-induced thrombocytopenia (DITP) is suggested by severe thrombocytopenia with subsequent recovery of platelet count after removal of the offending drug. The...
Drug-induced thrombocytopenia (DITP) is suggested by severe thrombocytopenia with subsequent recovery of platelet count after removal of the offending drug. The diagnosis is ascertained when there is reproducibility of thrombocytopenia with repeated exposure. Filgrastim is used during peripheral blood progenitor cell harvest during autologous stem cell transplantation in the setting of multiple myeloma to prolong event-free survival and overall mortality. The following case illustrates all of the suggestive features of DITP after filgrastim exposure during elective stem cell harvest. Due to the inability to tolerate filgrastim, autologous stem cell transplant was aborted in this patient and he was maintained on induction chemotherapy.
Topics: Filgrastim; Hematologic Agents; Hematopoietic Stem Cell Transplantation; Humans; Induction Chemotherapy; Lumbar Vertebrae; Male; Middle Aged; Multiple Myeloma; Pelvic Bones; Platelet Count; Preoperative Care; Thrombocytopenia; Transplantation, Autologous; Withholding Treatment
PubMed: 32606115
DOI: 10.1136/bcr-2020-234584 -
Blood Cancer Journal May 2017The aim of this cohort study was to compare a condensed schedule of consolidation therapy with high-dose cytarabine on days 1, 2 and 3 (HDAC-123) with the HDAC schedule... (Comparative Study)
Comparative Study Randomized Controlled Trial
The aim of this cohort study was to compare a condensed schedule of consolidation therapy with high-dose cytarabine on days 1, 2 and 3 (HDAC-123) with the HDAC schedule given on days 1, 3 and 5 (HDAC-135) as well as to evaluate the prophylactic use of pegfilgrastim after chemotherapy in younger patients with acute myeloid leukemia in first complete remission. One hundred and seventy-six patients were treated with HDAC-135 and 392 patients with HDAC-123 with prophylactic pegfilgrastim at days 10 and 8, respectively, in the AMLSG 07-04 and the German AML Intergroup protocol. Time from start to chemotherapy until hematologic recovery with white blood cells >1.0 G/l and neutrophils >0.5 G/l was in median 4 days shorter in patients receiving HDAC-123 compared with HDAC-135 (P<0.0001, each), and further reduced by 2 days (P<0.0001) by pegfilgrastim. Rates of infections were reduced by HDAC-123 (P<0.0001) and pegfilgrastim (P=0.002). Days in hospital and platelet transfusions were significantly reduced by HDAC-123 compared with HDAC-135. Survival was neither affected by HDAC-123 versus HDAC-135 nor by pegfilgrastim. In conclusion, consolidation therapy with HDAC-123 leads to faster hematologic recovery and less infections, platelet transfusions as well as days in hospital without affecting survival.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Consolidation Chemotherapy; Cytarabine; Daunorubicin; Disease-Free Survival; Female; Filgrastim; Humans; Length of Stay; Leukemia, Myeloid, Acute; Male; Middle Aged; Platelet Transfusion; Polyethylene Glycols; Survival Rate
PubMed: 28548643
DOI: 10.1038/bcj.2017.45 -
Journal of Clinical Oncology : Official... Dec 2020Relapse is a major cause of treatment failure after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) for high-risk acute myeloid leukemia (HR-AML). The aim... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of rhG-CSF Combined With Decitabine Prophylaxis on Relapse of Patients With High-Risk MRD-Negative AML After HSCT: An Open-Label, Multicenter, Randomized Controlled Trial.
PURPOSE
Relapse is a major cause of treatment failure after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) for high-risk acute myeloid leukemia (HR-AML). The aim of this study was to explore the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) combined with minimal-dose decitabine (Dec) on the prevention of HR-AML relapse after allo-HSCT.
PATIENTS AND METHODS
We conducted a phase II, open-label, multicenter, randomized controlled trial. Two hundred four patients with HR-AML who had received allo-HSCT 60-100 days before randomization and who were minimal residual disease negative were randomly assigned 1:1 to either rhG-CSF combined with minimal-dose Dec (G-Dec group: 100 µg/m of rhG-CSF on days 0-5 and 5 mg/m of Dec on days 1-5) or no intervention (non-G-Dec group). The primary outcome was relapse after transplantation, and the secondary outcomes were chronic graft-versus-host disease (cGVHD), safety of the treatment, and survival.
RESULTS
The estimated 2-year cumulative incidence of relapse in the G-Dec group was 15.0% (95% CI, 8.0% to 22.1%), compared with 38.3% (95% CI, 28.8% to 47.9%) in the non-G-Dec group ( < .01), with a hazard ratio (HR) of 0.32 (95% CI, 0.18 to 0.57; < .01). There was no statistically significant difference between the G-Dec and non-G-Dec groups in the 2-year cumulative incidence of cGVHD without relapse (23.0% [95% CI, 14.7% to 31.3%] and 21.7% [95% CI, 13.6% to 29.7%], respectively; = .82), with an HR of 1.07 (95% CI, 0.60 to 1.92; = .81). After rhG-CSF combined with minimal-dose Dec maintenance, increasing numbers of natural killer, CD8+ T, and regulatory T cells were observed.
CONCLUSION
Our findings suggest that rhG-CSF combined with minimal-dose Dec maintenance after allo-HSCT can reduce the incidence of relapse, accompanied by changes in the number of lymphocyte subtypes.
Topics: Adolescent; Adult; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Decitabine; Female; Filgrastim; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Prognosis; Recurrence; Risk Factors; Transplantation Conditioning; Young Adult
PubMed: 33108244
DOI: 10.1200/JCO.19.03277 -
Journal of Managed Care & Specialty... May 2021The first biosimilar product filgrastim-sndz was approved by the FDA in 2015, but real-world evaluations of its uptake and cost in nationally representative populations...
The first biosimilar product filgrastim-sndz was approved by the FDA in 2015, but real-world evaluations of its uptake and cost in nationally representative populations are limited. To evaluate the uptake and cost of filgrastim-sndz, relative to its originator filgrastim and alternative biologic tbofilgrastim, among Medicare and Medicaid populations. Using the annually aggregated, product-level utilization and cost data of biologic and biosimilar filgrastim products in 2015-2018 from CMS drug spending data, total number of claims and costs for all 3 filgrastim products were identified and extracted for Medicare Part B, Part D, and Medicaid reimbursement. Annual average cost per claim and per beneficiary of individual filgrastim products were also extracted, and their annual growth rates were calculated. Three years after entering the US market, use of filgrastim-sndz increased to 49.1% and 46.0% of all filgrastim claims paid by Medicare Parts B and D, respectively, and to 38.7% of filgrastim Medicaid claims in 2018. Total cost for filgrastim-sndz also reached 42.8%, 41.8%, and 26.9% of all filgrastim products paid by Medicare Parts B and D and Medicaid, respectively. Significant reductions in average cost per claim for filgrastim-sndz in 2017 and 2018 were observed in Medicare Part B and Medicaid. Significant uptake of biosimilar filgrastim in Medicare and Medicaid programs occurred during the first 3 years of marketing. Policymakers may use the evidence to evaluate existing barriers and policies regarding biosimilar adoption. No outside funding supported this work. The author has no conflicts of interest to disclose.
Topics: Biosimilar Pharmaceuticals; Drug Costs; Filgrastim; Hematologic Agents; Humans; Insurance Claim Review; Medicaid; Medicare Part B; United States
PubMed: 33908273
DOI: 10.18553/jmcp.2021.27.5.660 -
International Journal of Cancer Mar 2021Little is known about the benefits and risks of myeloid growth factor administration after chimeric antigen receptor (CAR) T-cell therapy for diffuse large B-cell...
Little is known about the benefits and risks of myeloid growth factor administration after chimeric antigen receptor (CAR) T-cell therapy for diffuse large B-cell lymphoma (DLBCL). We present a retrospective analysis among 22 relapsed/refractory DLBCL patients who received CAR T-cell therapy with axicabtagene ciloleucel. Filgrastim was administered by physician discretion to seven patients (31.8%), and the median duration of neutropenia after lymphodepleting therapy was significantly shorter for those patients who received filgrastim (5 vs 15 days, P = .016). Five patients (22.7%) developed infection in the 30 days post-CAR T-cell therapy with three patients being Grade 3 or higher. There was no difference in the incidence and severity of infection based on filgrastim use (P = .274, P = .138). Among the seven patients that received filgrastim, six patients (85.7%) and four patients (57.1%) had evidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), respectively. Among the 15 patients that did not receive filgrastim, 8 patients (53.3%) and 7 patients (46.7%) had evidence of CRS and ICANS, respectively. There was no significant difference in the incidence of developing CRS or ICANS between the group of patients that received filgrastim and those that did not (P = .193, P = .647). However, there was a significant increase in the severity of CRS for patients that received filgrastim compared to those that did not (P = .042). Filgrastim administration after CAR T-cell therapy may lead to an increase in severity of CRS without decreasing infection rates.
Topics: Aged; Cytokine Release Syndrome; Female; Filgrastim; Humans; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Neurotoxicity Syndromes; Neutropenia; Receptors, Chimeric Antigen; Retrospective Studies
PubMed: 33091961
DOI: 10.1002/ijc.33356 -
Journal of Oncology Pharmacy Practice :... Sep 2018Background Granulocyte colony-stimulating factors are effective at reducing the risk and duration of neutropenia. The current meta-analysis compared the... (Comparative Study)
Comparative Study Meta-Analysis Review
Background Granulocyte colony-stimulating factors are effective at reducing the risk and duration of neutropenia. The current meta-analysis compared the neutropenia-related efficacy and safety of lipegfilgrastim to those of pegfilgrastim and filgrastim. Methods Embase was searched for trials examining the efficacy/safety of lipegfilgrastim, pegfilgrastim, or filgrastim. Outcomes included febrile neutropenia, severe neutropenia, duration of severe neutropenia, time to recovery of absolute neutrophil count, and incidence of bone pain. Direct comparisons were made using random-effects models. No trials directly compared lipegfilgrastim and filgrastim. Indirect comparisons were made between lipegfilgrastim and filgrastim with pegfilgrastim as the common comparator. Results This meta-analysis included a total of 5769 patients from 24 studies. Over all cycles, lipegfilgrastim showed a lower, nonsignificant risk of febrile neutropenia compared with pegfilgrastim. Lipegfilgrastim has a lower risk of febrile neutropenia versus filgrastim but was also not statistically significant. The risk ratio for severe neutropenia in cycle 1 was 0.80, a 20% reduction in favor of lipegfilgrastim. For cycles 2-4, the risk ratio was 0.53 (0.35, 0.79) for lipegfilgrastim versus pegfilgrastim. The risk of severe neutropenia in cycles 2-4 was also significantly lower for lipegfilgrastim (risk ratio 0.45, 0.27, 0.75, respectively). No significant differences were found for febrile neutropenia and severe neutropenia in cycle 1. However, in cycles 2-4, lipegfilgrastim was associated with significant and clinically meaningful reductions in risk of severe neutropenia versus either pegfilgrastim or filgrastim. Conclusions Compared with pegfilgrastim or filgrastim, lipegfilgrastim has a statistically significantly lower absolute neutrophil count recovery time; however, differences in duration of severe neutropenia and bone pain were nonsignificant.
Topics: Antineoplastic Agents; Filgrastim; Humans; Neutropenia; Odds Ratio; Polyethylene Glycols
PubMed: 28614980
DOI: 10.1177/1078155217714859 -
Future Oncology (London, England) May 2019The recombinant G-CSF filgrastim was first approved in 1991, and its value has been evolving ever since. Initial health technology assessments suggested low value due to... (Review)
Review
The recombinant G-CSF filgrastim was first approved in 1991, and its value has been evolving ever since. Initial health technology assessments suggested low value due to high drug cost and no evidence for significant gain in overall survival. However, more recent meta-analyses of placebo-controlled randomized trial data show falling costs due to biosimilar competition and absolute overall survival gains of 3.2% (95% CI: 2.1-4.2%) from filgrastim support of cytotoxic chemotherapy. The launch of biosimilar alternatives merits a re-evaluation of decisions by health technology assessments and explains the first inclusion of filgrastim in the WHO Essential Drug List for cancer >20 years after its original approval in 1991, thus demonstrating the power of biosimilar medicines in transforming healthcare.
Topics: Biosimilar Pharmaceuticals; Filgrastim; Hematologic Agents; Humans; Neoplasms; Prognosis
PubMed: 30835142
DOI: 10.2217/fon-2018-0762