Incidence Of Febrile Neutropenia In Patients Research Articles

Effects of primary granulocyte-colony stimulating factor prophylaxis on the incidence of febrile neutropenia in patients with germ cell tumors.

Testicular germ cell tumors (GCTs) are the most common solid malignancy in males aged 15–35 years. Febrile neutropenia (FN) is a serious complication of chemotherapy that frequently occurs in patients with GCTs. The present retrospective study aimed to evaluate the effect of primary granulocyte-colony stimulating factor (G-CSF) prophylaxis on the incidence of FN in patients with GCTs. The present study included a review of the medical records of patients diagnosed with GCTs treated with first-line/adjuvant chemotherapy between January 2000 and December 2017 at the National Cancer Institute (Bratislava, Slovakia). In January 2006, a decision was made to administer G-CSF prophylaxis (filgrastim or pegfilgrastim) to patients after every cycle of chemotherapy. The present study included 385 patients, and out of these, 264 patients received primary G-CSF prophylaxis, while 121 patients did not. A total of 71 patients (18.4%) suffered from FN events. In the subgroup that did not receive primary prophylaxis, 42 patients exhibited FN, while only 29 patients with primary prophylaxis suffered from FN (34.7 vs. 11.0%; P=0.00000003). According to the subgroup analysis, FN incidence was decreased in all groups that received primary prophylaxis, except for patients with stage I GCT receiving adjuvant chemotherapy, without affecting overall survival. Primary G-CSF prophylaxis was associated with markedly reduced FN incidence in patients treated with first-line chemotherapy for metastatic disease. Therefore, the results of the present study suggested that primary G-CSF prophylaxis should be considered in patients with GCT receiving first-line chemotherapy.

A prospective study to evaluate febrile neutropenia incidence in patients receiving pegfilgrastim on-body injector vs other choices.

PurposeWe evaluated the incidence of febrile neutropenia (FN) and related clinical outcomes among patients treated with myelosuppressive chemotherapy for nonmyeloid malignancies who received pegfilgrastim on-body injector (OBI) or other options (Other) for FN prophylaxis.MethodsIn this prospective observational study, adult patients with breast, prostate, or lung cancer, or non-Hodgkin lymphoma at risk for FN were stratified into subgroups based on FN prophylaxis used in the first chemotherapy cycle: pegfilgrastim OBI vs Other (pegfilgrastim or biosimilar pegfilgrastim prefilled syringe, daily filgrastim, or no granulocyte colony–stimulating factor [G-CSF]) for up to 4 planned chemotherapy cycles.ResultsThis US study enrolled 2575 eligible patients (OBI, 1624; Other, 951). FN incidence was lower in the OBI group (6.4% [95% CI, 5.2–7.6%]) than in the Other group (9.4% [7.5–11.2%]), with a relative risk (RR) of 0.66 (0.47–0.91; p = .006). A decreased risk of dose delays among patients receiving pegfilgrastim OBI vs Other was observed (RR for ≥ 5 days: 0.64 [0.42–0.96], p = .023; RR for ≥ 7 days: 0.62 [0.40–0.91], p = .016). Adherence, defined as G-CSF support for all chemotherapy cycles, was 94.0% (92.9–95.2%) in the OBI group compared with 58.4% (55.2–61.5%) in the Other group. Compliance with pegfilgrastim, defined as administration the day after chemotherapy, was 88.3% in the OBI group and 48.8% in the prefilled syringe group.ConclusionPatients receiving pegfilgrastim OBI had a lower incidence of FN compared with those receiving alternatives. The OBI was associated with improved adherence to and compliance with clinically recommended G-CSF prophylaxis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00520-022-07226-9.

A prospective cohort study to evaluate the incidence of febrile neutropenia in patients receiving pegfilgrastim on-body injector versus other options for prophylaxis of febrile neutropenia: breast cancer subgroup analysis

BackgroundBreast cancer chemotherapy often carries a high risk of febrile neutropenia (FN); guidelines recommend prophylaxis with granulocyte colony-stimulating factor (G-CSF), such as pegfilgrastim. Neulasta® Onpro® on-body injector (OBI) is a delivery device administering pegfilgrastim approximately 27 h after application.MethodsThis prospective study examined patients with breast cancer who received chemotherapy with a high risk of FN, receiving OBI (“OBI”) or other options (other G-CSF or none; “other”). The primary endpoint was FN incidence; secondary endpoints included chemotherapy delivery, adherence (G-CSF in all cycles), compliance (G-CSF day after chemotherapy), and FN incidence in patients receiving curative or palliative treatment.ResultsA total of 1776 patients with breast cancer were enrolled (OBI, n = 1196; other, n = 580). Across all cycles, FN incidence was lower for OBI (4.4% [95% CI, 3.3–5.6%]) than other (7.4% [5.3–9.6%]). For curative treatment, the FN incidence across all cycles was lower for OBI (4.6% [3.4–5.8%]) than for other (7.1% [5.0–9.3%]). For palliative treatment (OBI, n = 33; other, n = 20), 3 patients (15%) in the other and none in the OBI group had FN. After adjusting for baseline covariates, FN incidence remained lower for OBI (4.6% [3.5–6.1%]) versus other (7.8% [5.7–10.5%]). Adherence was higher for OBI (93.8%) than for other G-CSF (69.8%), as was compliance (90.5 and 53.2%, respectively). Chemotherapy dose delays/reductions were similar for OBI (4.7%/32.3%, respectively) and other (4.7%/30.0%) groups.ConclusionPegfilgrastim OBI was associated with a lower FN incidence in patients with breast cancer compared to other options for FN prophylaxis.Trial registrationwww.clinicaltrials.gov, NCT02178475, registered 30 June, 2014

Predictive Parameters of Febrile Neutropenia and Clinical Significance of G-CSF Receptor Signaling Pathway in the Development of Neutropenia during R-CHOP Chemotherapy with Prophylactic Pegfilgrastim in Patients with Diffuse Large B-Cell Lymphoma.

PurposePegfilgrastim is widely used to prevent chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) in patients with diffuse large B-cell lymphoma (DLBCL). We investigated the predictive factors affecting CIN and FN incidence in patients with DLBCL receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy with pegfilgrastim and conducted experiments to find reason for the occurrence of CIN even when pegfilgrastim was used.Materials and MethodsWe reviewed the CIN and FN events of 200 patients with DLBCL. Based on these data, we investigate the association with predictive factor and the levels of granulocyte-colony stimulating factor (G-CSF) receptor signaling pathway markers (pSTAT3, pAKT, pERK1/2, pBAD, and CXCR4) in bone marrow (BM) samples isolated from patients with DLBCL.ResultsFN was significantly associated with stage III/IV (hazard ratio [HR], 12.74) and low serum albumin levels (HR, 3.87). Additionally, patients with FN had lower progression-free survival (PFS; 2-year PFS, 51.1 % vs. 74.0%) and overall survival (OS; 2-year OS, 58.2% vs. 85.0%) compared to those without FN. The occurrence of CIN was associated with overexpression of G-CSF receptor signaling pathway markers, and expression levels of these markers were upregulated in BM cells co-cultured with DLBCL cells. The rate of neutrophil apoptosis was also higher in neutrophils co-cultured with DLBCL cells and was further promoted by treatment with doxorubicin.ConclusionOur findings suggest that high DLBCL burden may alter the BM environment and G-CSF receptor signaling pathway, even in chemotherapy-naïve state, which may increase CIN frequency during R-CHOP chemotherapy.

Systematic review and meta-analysis of febrile neutropenia risk with TCH(P) in HER2-positive breast cancer.

Docetaxel, carboplatin and trastuzumab, with or without pertuzumab (TCH(P)), has become the preferred (neo)adjuvant regimen for HER2-positive breast cancer. However, its associated febrile neutropenia (FN) risk is unclear: pivotal studies reported FN risks < 10%, but in clinical practice, a high FN rate (> 20%) was observed. This systematic review and meta-analysis determine the FN risk associated with TCH(P) and the indication for primary prophylactic granulocyte colony-stimulating factor (PP G-CSF). The MEDLINE, Embase, Web of Science and Cochrane databases were searched for full-text English articles reporting the FN incidence in early breast cancer patients receiving (neo)adjuvant TCH(P). The primary endpoint was the pooled crude FN incidence in patients treated without PP G-CSF using the random effects method. Secondary endpoints were the FN risk with PP G-CSF support, age-related differences in FN and differences in risk with TCH versus TCHP. Seventeen studies were included in the systematic review. The pooled estimates of FN incidences were 27.6% (95% CI 18.6 to 37.1) in patients who did not receive PP G-CSF (primary meta-analysis, 9 studies, n = 889) versus 5.0% (95% CI 2.6 to 8.0) in patients administered PP G-CSF (secondary meta-analysis, 7 studies, n = 445). Two studies reported non-significant age-related differences in FN. The risk comparison between TCH and TCHP was inconclusive. The crude FN risk associated with (neo)adjuvant TCH(P) is over 20%, the upper limit above which the international guidelines unanimously advise PP G-CSF administration. G-CSF prophylaxis effectively reduces FN risk and should become the standard of care with (neo)adjuvant TCH(P).

Transition of dose-adjusted EPOCH therapy into the outpatient healthcare setting, quality and cost considerations under an alternate payment model.

e18655 Background: Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin DA-(EPOCH)-containing regimens are frequently utilized in lymphoma, however, outpatient EPOCH or modified inpatient/outpatient EPOCH has not been described extensively. We transitioned inpatient EPOCH to the outpatient setting and modified EPOCH to be given in the inpatient setting with rituximab outpatient to improve quality of care and access to patient assistance programs. Methods: A single-center, institutional review board-approved retrospective study was conducted for adults receiving EPOCH-based regimens. Data were collected by chart review for each patient between January 2013 and September 2020. The primary outcomes were to determine the incidence of chemotherapy delays due to disease-related reasons as febrile neutropenia (FN), adverse events or abnormal labs and the incidence of FN between patients receiving inpatient (IP), outpatient (OP), or combination inpatient/outpatient DA-EPOCH +/- R (hybrid). Secondary cost analysis including hospital stay cost, chemotherapy and laboratory monitoring costs was performed for the three settings. Results: A total of 43 patients received 175 cycles of an EPOCH regimen (18 [10.3%] IP), 90 [51.4%] OP, and 67 [38.3%] hybrid). The mean maximum dose level achieved with DA-EPOCH+/-R was dose level 2 with the average number of cycles at 4.1 cycles/patient. A total of 15 cycles were delayed due to disease related reasons: 1 (6%) in IP, 12 (18%) in hybrid (P = 0.196, when compared with IP) and 2 (2%) in OP (P = 0.432 when compared with IP). A total of 166 cycles received granulocyte-colony stimulating factor (G-CSF); 16 cycles (9.6%) administered IP with a FN incidence of two (12.5%), 62 cycles (37.4%) administered in the hybrid setting with a FN incidence of seven (11.3%) (P = 0.893 when compared with IP) and 88 cycles (53%) administered OP with a FN incidence of ten (11.3%) (P = 0.896 when compared with IP). The incidence of FN was 9.3% and 12.7% in patients received pegfilgrastim same day versus next day, respectively, P = 0.558. The incidence of FN in patients received reference pegfilgrastim was 9.5% vs 7.7% for patients received pegfilgrastim-cbqv in OP setting (P = 1.00). Transitioning EPOCH to a hybrid IP/OP or OP setting yielded a total cost savings to the health-system of $3,523,174 with 607 hospital bed days saved. Conclusions: EPOCH-containing regimens can be safely transitioned into the outpatient setting or utilized as a hybrid of EPCOH and outpatient Rituximab after chemotherapy side effects can be monitored and outcomes optimized, to better adapt treatment strategies for individualized patient therapies. As new healthcare payment models are developed, outpatient treatments allow for adaptive financial options both for the payor and the patient.

Retrospective Analysis of Clinical Outcomes Associated With the Use of Pegfilgrastim On-body Injector in Patients Receiving Chemotherapy Requiring Granulocyte Colony-Stimulating Factor Support.

Objectives: Pegfilgrastim is a granulocyte colony-stimulating factor (G-CSF) used as primary prophylaxis in patients receiving myelosuppressive chemotherapy regimens that have greater than 20% risk of developing febrile neutropenia (FN). Historically, pegfilgrastim has been administered 24 to 72 hours after chemotherapy, necessitating a return to clinic to receive the provider-administered injection. An alternative option is the pegfilgrastim on-body injector (OBI). With the OBI device, patients have their pegfilgrastim administered 27 hours after receiving chemotherapy while remaining at home, avoiding an additional clinic appointment. Concerns with pegfilgrastim OBI include lack of experience with the device in both the patient and provider, device-related failures, and the success of delivery. This study evaluates pegfilgrastim OBI failure rates through associated patient outcomes among cancer patients receiving chemotherapy requiring G-CSF. Methods: A retrospective electronic chart review was conducted of adult patients with cancer who received chemotherapy and pegfilgrastim OBI from July 1, 2016, to July 31, 2018. The primary objective of this study was the incidence of FN in patients receiving pegfilgrastim OBI. Results: There were no reported cases of hospitalization due to FN in patients who received pegfilgrastim OBI. Dose delays and dosage modifications were not observed in our review. The OBI device failure rate was found to be low (1.92%). Conclusion: The low device failure rate from this study suggests that the OBI is a viable option for administration of pegfilgrastim in patients receiving chemotherapy requiring G-CSF.

Primary prophylactic granulocyte colony-stimulating factor according to ASCO guidelines has no preventive effect on febrile neutropenia in patients treated with docetaxel, cisplatin, and 5-fluorouracil chemotherapy.

The efficacy of primary prophylactic granulocyte colony-stimulating factor (G-CSF) in preventing febrile neutropenia (FN) in patients treated with docetaxel, cisplatin, and 5-fluorouracil (TPF) chemotherapy remains controversial. We compared the incidence of FN in patients treated with and without primary prophylactic G-CSF. We performed a retrospective analysis of 142 patients with locally advanced head and neck or esophageal cancer treated with TPF between January 2009 and March 2017. Among them, 116 patients started TPF without primary prophylactic G-CSF (control group) while 26 patients were given primary prophylactic G-CSF from day 7 of the first cycle of TPF (prophylactic group). The incidence of grade 4 neutropenia during the first cycle of TPF was significantly higher in the control group than in the prophylactic group [58.6% (n = 68) vs. 30.8% (n = 8), p = 0.02]. However, the incidence of FN in the first cycle was not significantly different between the two groups [32 patients (27.5%) in the control group and 8 patients (30.8%) in the prophylactic group (p = 0.62)]. In addition, the mean relative dose intensity throughout all cycles of TPF, as well as the survival time and response after TPF, were also not significantly different between the two groups. Primary prophylactic G-CSF from day 7 of the first cycle of TPF did not reduce the incidence of FN. Our findings suggest that the timing of primary prophylactic G-CSF, as recommended by the American Society of Clinical Oncology guidelines, should be modified to reduce the incidence of FN in TPF.

Optimal timing for pegfilgrastim administration in Japanese breast cancer patients receiving intermediate-risk chemotherapies.

Background Pegfilgrastim is widely used for prophylaxis of febrile neutropenia (FN) in cancer patients receiving chemotherapies. However, the optimal timing of pegfilgrastim administration has not been established. Objective We investigated the effect of the timing of pegfilgrastim administration on the prevention of FN in patients with breast cancer undergoing intermediate-risk chemotherapies. Method We retrospectively analysed the incidence of FN in patients with breast cancer treated at our institution with intermediate-risk chemotherapies and primary or secondary prophylactic pegfilgrastim between 2015 and 2017. The impact of the timing of pegfilgrastim administration on the incidence of FN was evaluated by univariate and multivariate logistic regression analyses. Results Overall, 87 patients received a total of 318 chemotherapy cycles with pegfilgrastim, and 14 patients (16%) experienced FN. In univariate analyses, day 2 pegfilgrastim administration, age of > 65years, baseline haemoglobin < 12g/dL, prior history of FN, and presence of recurrent/metastatic disease trended toward an association with FN. Adjustment for these confounding risk factors revealed that day 2 pegfilgrastim administration was associated with a significantly increased risk of FN (odds ratio 11.0, p = 0.009). Conclusion Administrating pegfilgrastim on day 3 or later may prevent FN more effectively among Japanese breast cancer patients receiving intermediate-risk chemotherapies.

Association of risk of febrile neutropenia (FN) with docetaxel in prostate cancer (PC) patients: A meta-analysis of published phase II-III trials.

e21683 Background: Reported rates of FN with docetaxel (DTX) in PC patients are variable. This creates uncertainty regard the use of granulocyte colony-stimulating factor primary prophylaxis (G-CSF) in this setting. We conducted a meta-analysis of randomized clinical trials to determine the relative risk (RR) of FN in patients receiving DTX. Methods: To perform this analysis we systematically searched in PUBMED and MEDLINE database the following terms: “DTX”, “randomized clinical trial” and “prostate cancer” only for articles published between January 1996 and August 2016. Phase II-III clinical studies comparing DTX to non-DTX control arms (best supportive care [BSC] including non-cytotoxic therapy or mitoxantrone) for PC were included. The meta-analyses were performed by computing RRs with 95% confidence intervals (CI) using fixed-effects model with the Mantel-Haenszel method. Results: Seven studies (N = 5088 patients) were included. The global incidence of FN in patients treated with DTX was 10.7%. The RR of FN was higher in patients receiving DTX compared to patients did not receive DTX (RR 16.8 [95% CI 10.7; 26.4] p &lt; 0.0001). 6.6% of patients with metastatic castration resistant prostate cancer (CRPC) treated with DTX developed FN, the RR of FN with DTX compared to mitoxantrone was 28.6 (95% CI 5.6; 145.1). 12.4% of patients with hormone-sensitive prostate cancer (HSPC) treated with DTX developed FN, the RR of FN was 15.3 (95% CI 9.6; 24.6) compared to BSC. There was no statistically significant differences in the rate of FN according to the hormone sensitivity (HSPC vs CRPC) (p = 0.7). In most studies the use of G-CSF was at the discretion of the investigator. Conclusions: This meta-analysis shows that DTX is associated with a significant increase in the relative risk of FN in patients with PC. The effectiveness of primary prophylactic G-CSF in this setting has not been fully established. The incidence reported here does not meet the threshold recommended by ESMO and ASCO guidelines for the use of prophylactic G-CSF. Special attention should be given to high risk groups for FN, including elderly patients and those with bone marrow involvement or previous radiotherapy/chemotherapy.

A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Pegfilgrastim in Patients Receiving First-Line FOLFOX/Bevacizumab or FOLFIRI/Bevacizumab for Locally Advanced or Metastatic Colorectal Cancer: Final Results of the Pegfilgrastim and Anti-VEGF Evaluation Study (PAVES)

BackgroundPegfilgrastim's role in reducing the risk of febrile neutropenia (FN) in patients with colorectal cancer (CRC) receiving chemotherapy plus bevacizumab was not previously evaluated in a prospective study. The present phase III, double-blind trial evaluated the efficacy of pegfilgrastim versus placebo in reducing the incidence of grade 3/4 FN in patients with advanced CRC receiving bevacizumab combined with first-line chemotherapy (FOLFOX [leucovorin, 5-fluorouracil, oxaliplatin] or FOLFIRI [leucovorin, 5-fluorouracil, irinotecan]). Patients and MethodsPatients aged ≥ 18 years with locally advanced or metastatic CRC were randomized 1:1 to placebo or 6 mg of pegfilgrastim ∼24 hours after receiving chemotherapy plus bevacizumab every 14 days. The study treatment period included 4 cycles, but patients could continue treatment for ≤ 60 months. The primary endpoint was incidence of grade 3/4 FN in the first 4 cycles. The secondary endpoints included the objective response rate (ORR), overall survival, and progression-free survival, analyzed at the end of the long-term follow-up period. ResultsA total of 845 patients were randomized from November 2009 to January 2012 (422, pegfilgrastim; 423, placebo). Pegfilgrastim significantly reduced the incidence of grade 3/4 FN in the first 4 treatment cycles (pegfilgrastim, 2.4%; 95% confidence interval [CI], 1.1%-4.3%; placebo, 5.7%; 95% CI, 3.7%-8.3%; odds ratio [OR], 0.41; P = .014). No significant differences were observed between the 2 arms in ORR (OR, 1.15; P = .330), overall survival (hazard ratio, 0.94; P = .440), and progression-free survival (hazard ratio, 0.93; P = .300). ConclusionPegfilgrastim reduced the FN incidence in patients with advanced CRC receiving chemotherapy and bevacizumab. Administration of pegfilgrastim was tolerable and did not negatively affect the tumor response or survival in this patient population.

Lipegfilgrastim in patients with chemotherapy-induced neutropenia

The development of dose-limiting toxicities, including myelotoxicity, can significantly limit cytostatic therapy of malignant tumors. Neutropenia associated with high risk of febrile neutropenia (FN) and infectious complications that may interfere with therapy intensity and significantly increases the cost of diagnosis and treatment. With the development of recombinant forms of human granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor, therapy of iatrogenic neutropenia has undergone significant changes. The use of G-CSF (filgrastim, lenograstim, pegfilgrastim) reduces FN incidence in patients receiving myelosuppressive chemotherapy. Until recently, the only original preparation of G-CSF with prolonged action was pegfilgrastim. Lipegfilgrastim (Lonquex, Teva) is a new highly effective long-acting pegylated G-CSF, which has been approved by European Medicines Agency experts for FN prevention in patients receiving chemotherapy. This review summarizes the characteristics of chemical structure, pharmacokinetics, safety and efficacy of lipegfilgrastim.

Prophylactic Biosimilar Filgrastim Treatment during Cytotoxic Chemotherapy in Patients with Malignant Diseases: The Venice Observational Study

▪Introduction: Among other serious adverse events, febrile neutropenia (FN) is a serious, frequent complication associated with cytotoxic chemotherapy (CT). Biosimilar filgrastim (NivestimTM, Hospira Inc.) is a granulocyte-colony stimulating factor (G-CSF)approved for use in Europe since 2010 for the reduction in the duration of neutropenia and the incidence of FN in patients treated with cytotoxic CT for malignancy. The VENICE study was conducted to observe the tolerability, safety and efficacy of prophylactic treatment using biosimilar filgrastim among in-patients receiving cytotoxic CT for cancer outside the clinical trial setting in the context of real-life, day-to-day medical practice. This study is of particular relevancy due to the propensity for biosimilar G-CSF to lower overall costs of cancer treatment. ClinicalTrials.gov Identifier: NCT01627990Study Design: The study was conducted as a prospective, non-interventional study at 48 sites in Germany. Patients being treated for solid tumors or malignant hematologic tumors except for chronic myeloid leukemia (CML) or myelodysplastic syndrome (MDS) who had provided informed consent and for whom cytotoxic CT and biosimilar filgrastim treatment was planned were enrolled in the study. Data on demographics, clinical characteristics, treatment-related data on efficacy and safety (AEs including FN) and hospitalizations were collected. Three study visits were planned: at recruitment, at end of first biosimilar filgrastim administration and at end of CT or end of study.Results: The study included 386 adult patients undergoing cytotoxic CT who were treated with biosimilar filgrastim prophylactically to reduce the duration of neutropenia and to reduce incidence of chemotherapy-induced FN. Patients were 81% female with a mean age of 60 years. At baseline, 43% of the patients had already received CT and previous FN was reported by only 3% of patients. A total of 338 patients (88%) had solid tumors and 49 (13%) had hematological malignancies. Antibiotic prophylaxis was taken by 13% of patients at inclusion. Only 9% of the patients had received G-CSF from the first cycle. The majority (64%) of patients received biosimilar filgrastim as primary prophylaxis and 36% as secondary prophylaxis.At least one hospitalization was reported by 24 (6%) of 382 patients in the safety analysis set and the median hospital stay for these patients was 10 days. Hospitalization due to FN or infection was reported for 2% of patients.Only 1% of patients had a delay in their CT due to FN after the first biosimilar filgrastim treatment and for only 5% of patients, the CT in any subsequent CT cycle was delayed due to neutropenia. Reduction of CT dose after first biosimilar filgrastim treatment due to FN was reported for only 1% of patients and reduction of CT dose in any subsequent cycle due to neutropenia was reported for only 5% of patients.The median duration between the last dose of CT and treatment with biosimilar filgrastim was 5 days. The majority of patients were prescribed the 30 million units (MU) dose of biosimilar filgrastim administered SC. The median duration of treatment was 4 days. Most patients administered the biosimilar filgrastim injection themselves at both treatment visits (78% at first visit and 69% at last visit). Most of the self-applicators reported that the application was easy or very easy.During the study, 24% of patients experienced ≥1 AE that was at least possibly related to biosimilar filgrastim treatment. The treatment related AEs reported most frequently were musculoskeletal and connective tissue disorders (11%); general disorders and administration site conditions (5%); and blood and lymphatic system disorders (5%).Conclusions: The VENICE non-interventional study aimed to evaluate the use of biosimilar filgrastim according to the label approved usage of the biosimilar filgrastim in order to collect additional real world data on the tolerability, safety and efficacy in cancer patients. Biosimilar filgrastim was effective and well-tolerated in both the primary and secondary prophylactic settings in patients undergoing chemotherapy for solid tumors and hematological malignancies. DisclosuresErdlenbruch:Hospira Germany: Employment.

Attitudes of physicians toward assessing risk and using granulocyte colony-stimulating factor as primary prophylaxis in patients receiving chemotherapy associated with an intermediate risk of febrile neutropenia.

Febrile neutropenia (FN) is a potentially fatal complication of chemotherapy. This prospective, observational study describes physicians' approaches toward assessing FN risk in patients receiving chemotherapy regimens with an intermediate (10-20%) FN risk. In the baseline investigator assessment, physicians selected factors considered important when assessing overall FN risk and deciding on granulocyte colony-stimulating factor (G-CSF) primary prophylaxis (PP). Physicians then completed patient assessments using the same lists of factors. The final FN risk scores and whether G-CSF PP was planned were reported. The final analysis included 165 physicians and 944 patients. The most frequently considered factor in both assessments was chemotherapy agents in the backbone (88% of investigator and 93% of patient assessments). History of FN (83%), baseline laboratory values (76%) and age (73%) were commonly selected at baseline, whereas tumor type (72%), guidelines (62%) and tumor stage (43%) were selected most during patient assessments. Median investigator-reported FN risk threshold for G-CSF PP was 20% (range 10-85%). G-CSF PP was planned in 82% of patients with an FN risk at or above this threshold; therefore, almost one-fifth of qualifying patients would not receive G-CSF PP. Physicians generally follow guidelines, but also consider individual patient characteristics when assessing FN risk and deciding on G-CSF PP. A standardized FN risk assessment may optimize the use of G-CSF PP, which may minimize the incidence of FN in patients undergoing chemotherapy with an intermediate FN risk. ClinicalTrials.gov Identifier: NCT01813721.

Timing of Primary Prophylaxis G-CSF Use during Chemotherapy in Elderly Patients with NHL

Background: Febrile neutropenia (FN) and hospitalizations for infection are serious potential complications of myelosuppressive chemotherapy (chemo) treatment in cancer patients. Primary prophylactic G-CSF (PPG) is often used to decrease incidence of FN in patients at high risk. Due to the potential for G-CSF to stimulate neutrophil precursors at the same time as myelosuppression from chemotherapy, it is recommended that G-C SF be administered 24 hours after chemo administration. In addition, several studies showed that use of G-CSF on the same day as chemo may result in worse FN outcomes. Data are limited describing practice patterns of PPG timing relative to chemo administration in elderly patients with non-Hodgkin’s lymphoma (NHL), overall and by agent.Methods: The study population included non-HMO enrollees in the 20% Medicare sample with Parts A and B coverage who had NHL and initiated the first course of chemo between July 1, 2007, and November 30, 2011. PPG was defined as G-CSF initiated during days 0-5 of the first cycle, with day 0 the start of the chemo course. In patients with PPG, type of agent prescribed [Filgrastim (FIL), Sargramostim (SAR), or Pegfilgrastim(PEG)], timing of PPG initiation relative to chemo start date overall and by agent, and duration of prophylactic use (for the daily use agents FIL and SAR) were examined. Counts and percentages were estimated.Results: The study cohort included 13,402 patients with NHL; 2690 (20.1%) received PPG. In these patients, the most common PPG agent used was PEG (2471; 91.9%) followed by FIL (171; 6.4%) and SAR (48; 1.8%). The median [interquartile range] of course duration (in days) for the daily use agents was 3.5 [2, 5] for FIL and 3 [1.5, 5] for SAR. Overall, first G-CSF use within the prophylactic period peaked on the day after chemo initiation (day 1, 47.3%) and steadily decreased from day 2 (22%) to day 5 (4%). About 5% of patients received PPG on the same day as chemo (day 0). Patterns were similar by agent type (Figure). More PPG with FIL than with PEG was used on days 4 and 5.Conclusion: Use of prophylactic growth factor support is the recommended standard of care for patients at high risk of neutropenic infection. Consistent with the recommendations, PPG began most often on the day after chemo initiation regardless of agent type and more PPG with FIL started on day 4 or 5 after chemo initiation. [Display omitted] Note: Ten or fewer patients with SAR on days 0, 3-5. Results are not shown. DisclosuresPage:Amgen Inc.: Employment, Equity Ownership. Barron:Amgen Inc.: Employment, Equity Ownership. Morrow:Amgen Inc.: Employment, Equity Ownership. Stryker:Amgen Inc.: Employment, Equity Ownership. Acquavella:Amgen Inc.: Employment, Equity Ownership. Collins:ZS Pharma Inc.: Consultancy; Keryx Biopharmaceuticals, Inc.: Consultancy; Amgen Inc.: Consultancy; NxStage Medical Inc.: Consultancy.

P1-23-2 - Predicting Febrile Neutropenia From Docetaxel(Dtx)-Based Therapy in a Population-Based Analysis of Solid Tumor Patients

Background: Febrile neutropenia(FN) is a life-threatening complication of DTX therapy. It was reported that clearance of DTX associated with α1-acid glycoprotein, serum albumin level(ALB), CYP3A activity, liver dysfunction, and so on. This study aimed to identify predictive factors of DTX-induced FN.Methods: We investigated the incidence of FN in patients(pts) treated with DTX at the Osaka National Hospital from Apr 2008 to Oct 2013. The data obtained during the first 21 days were used for an analysis in the present study. We conducted to explore factor associated with FN by pts treated with DTX alone dose of 60mg/m2. Then we examined the validity of predictive factors in different doses and DTX-based combination therapy.Results: In total, 791 pts were included: 347 treated by monotherapy and 444 by combination therapy. Univariate analysis identified CYP3A inhibitor (≥moderate), PS (≥2), ALB, ALP and liver dysfunction (AST and/or ALT > 1.5xULN concomitant with ALP > 2.5xULN) as significant predictive factors; CYP3A inhibitor (≥moderate) and ALB was also an independent predictive factor in multivariable analysis at DTX alone dose of 60mg/m2. As the results of ROC analysis, optimal cut-off value of ALB associated with FN occurrence was determined to 3.2g/mL (AUC: 0.78). The incidence of FN was significantly higher in 63% of pts with ALB ≤3.2mg/dL compared with 11% of pts with ALB > 3.2mg/dL (OR:13.6, p < 0.0001). On the other hand, it was no difference in the incidence of FN in pts treated with DTX alone dose of ≤40mg/m2. Although combination therapy was similar to trend of monotherapy, the incidence of FN was frequent regardless of predictive factors in platinum-based triplet therapy.Conclusions: On the dose setting of DTX, it should be referring to ALB and combination of CYP3A inhibitors. Results of this study might suggest needs of dose reduction to ≤40mg/m2 in patients with ALB ≤3.2g/mL or combined with CYP3A moderate and strong inhibitors.

OPERa Study

On the whole, most European and international guidelines recommend prophylactic use of granulocyte-colony stimulating factors (G-CSFs) when the risk of chemotherapy-induced febrile neutropenia (FN) in cancer patients exceeds 20%. In patients treated with intermediate-risk chemotherapy regimens the recent EORTC guidelines recommend to consider supplementary patient-related adverse risk factors such as elderly age ( 65 years) prior to administrating each cycle of chemotherapy. The primary objective of our study is to describe the most important FN risk factors that underlie the use of pegfilgrastim PP in daily practice in the Czech Republic; secon-dary endpoints include FN incidence, chemotherapy dose intensity, anti-infective agents admini-stration, hospitalization length and safety of chemotherapy regimens. This prospective, multicenter, non-interventional study enrolled patients receiving a chemotherapy with high FN risk ( 20% according to EORTC guidelines) based on investigators` assessment. Data were collected on a total of 333 patients treated for breast cancer (69%), lymphoma (20%), ovarian (5%), lung (4%) and testicular cancer (1%). The most frequent indications for G-CSF prophylaxis were myelotoxic chemotherapy regimen (96%), elderly age (36%), advanced stage disease (35%), female gender (30%), cancer type (15%) and previous FN episode (12%). The overall FN incidence was 3% in patients receiving primary pegfilgrastim prophylaxis (n = 210) and 12% in patients with no pegfilgrastim PP (n = 123). The myelotoxicity of a chemotherapeutic regimen was the most significant FN risk factor identified by the inquired physicians. The second most compelling FN risk factor was elderly age and advanced stage disease. FN incidence in patients who received pegfilgrastim PP was relatively low in comparison to the commonly expected FN incidence in a population of patients receiving a chemotherapy regimen with high risk of FN.

P5-18-05: Incidence of Febrile Neutropenia in Patients Treated with Docetaxel and Cyclophosphamide (TC) for Adjuvant Breast Cancer.

Abstract Background: Adjuvant docetaxel with cyclophosphamide (TC) chemotherapy use in the community is common based on its improved disease outcomes compared to doxorubicin with cyclophosphamide (AC) treatment, lack of cardiac toxicity associated with anthracyclines, and perceived low incidence of febrile neutropenia (FN). In the pivotal trial of AC versus TC, the incidence of FN in breast cancer patients who received TC treatment was 4% in patients under 65 years and 8% in patients greater than 65 years. Growth factors (CSF) were not used in the trial, but antibiotics were used significantly. FN rates of 11.6% to 50% have been reported in multiple small studies, prompting warnings that primary prophylaxis with growth factor should be used. The true incidence of FN in community based patients may be higher than in the original clinical trial population as non-trial patients may have risk factors known to increase the risk for chemotherapy-induced FN, including increased age or other comorbid conditions. We wanted to know the incidence of FN in patients receiving TC chemotherapy who were not given primary prophylaxis with CSF. Methods: Using our electronic medical record system, a retrospective review of patients starting TC for breast cancer in 2010 at Kaiser Permanente Northern California was included. Patients had started a four or six cycle regimen of docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 every 21 days. Patients were stratified into two groups: (1) CSF primary prophylaxis given with the first cycle versus (2) no CSF primary prophylaxis given with the first cycle. CSF prophylaxis was given by physician choice. FN episodes were defined with a clinical diagnosis code for FN from emergency department visits or hospitalizations. The primary outcome was the incidence of TC-induced FN in patients who did not receive CSF primary prophylaxis with the first cycle of treatment. Results: 332 patients with a mean age of 57.9 years (range 30.5 to 83.6 years) were included. Of these, 204 (61.4%) did not receive primary CSF prophylaxis (mean age 57.4 years, range 30.5 to 83.6 years), and 128 (38.6%) received primary CSF prophylaxis (mean age 58.5 years, range 36.6 to 82.4 years). The incidence of FN during any cycle was 24.5% (50/204) in those who did not receive primary CSF prophylaxis and 8.6% (11/128) in those who did (p=0.0003). Patients were hospitalized for FN for a total of 174 days (mean 3.2 days, range 1 to 13 days). Mean days hospitalized were 3.2 in each group. We will present risk factors associated with the development of FN. Conclusion: In the largest population based report to date, we report the incidence of febrile neutropenia to be 24.5% in patients not receiving primary CSF prophylaxis. The rate is higher than originally reported for TC. Primary prophylaxis with CSF should be considered when treating this patient population with TC chemotherapy. Further analysis, including risk factor assessment, will be presented. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-18-05.

Optimizing Premedications In the Prevention of Bendamustine Infusion Related Reactions

AbstractAbstract 4370 IntroductionBendamustine is indicated for the treatment of CLL and rituximab-refractory indolent NHL. Clinical trials have reported 25% incidence of infusion related reactions (IRR) in patients receiving bendamustine. While these reactions are well documented, there is no consensus on the optimal premedication regimen for the prevention of these adverse effects. The Moffitt Cancer Center (MCC) utilizes a regimen of ondansetron 16 mg PO and dexamethasone 10 mg IVP prior to each bendamustine infusion. Herein, we report our experience with our current premedication regimen with regards to the IRR as well as the incidence of febrile neutropenia (FN). MethodsWe retrospectively analyzed 79 consecutive patients receiving bendamustine infusions at MCC from June 2008 to June 2010 to determine the incidence of IRR and FN. Data collected include baseline laboratory values, diagnosis, dosing, number of bendamustine infusions, concurrent rituximab use, growth factor utilization, as well as safety data including the rate of adverse reactions, interventions, and hospitalization. The primary objective was to determine the incidence of IRR. Secondary objectives include incidence of febrile neutropenia and hospital admission rate. All analyses were performed using SPSS 17.0. Descriptive statistics were used to analyze data. Results79 consecutive patients received a total of 513 bendamustine infusions at MCC. Median age was 68 years; M:F (52:27). The most common primary malignancies were indolent non-Hodgkin's lymphoma (NHL), 56%; chronic lymphocytic leukemia (CLL), 38%; and multiple myeloma (MM) 6.3%. Patients had received a median of 2 regimens prior to initiation of bendamustine. Bendamustine was utilized as first line treatment in 25% of patients, second line in 17.7%, third line in 25%, and fourth line or greater in 32.3% of patients. Bendamustine infusions were well-tolerated. Infusion-related reactions (IRR) occurred at a rate of 3.35% (17/513) with all reactions attributed to rituximab. Most commonly reported reactions reported were rigors (2%), chills (1%), and fever (<1%). IRR did not occur in patients receiving bendamustine alone. Overall incidence of FN was 11% (9/79). Of 9 patients that developed FN, 7 patients received bendamustine as 3rd line treatment or greater. The incidence of FN in patients that received bendamustine as 1st or 2nd line treatment was 6% (2/36). Patients that received bendamustine as 3rd line or greater had a 16% (7/43) incidence of FN. ConclusionBased on our experience with bendamustine, ondansetron and dexamethasone provide safe and effective prevention of infusion related reactions associated with bendamustine. Notably, all infusion reactions were attributed to rituximab infusions and no patients experienced an infusion related reaction when receiving bendamustine alone. This compares favorably to the initial reported infusion-related reactions with bendamustine alone (25%). In avoiding the use of other premedications, the likelihood of additional complications or adverse affects can be minimized. The overall incidence of FN was comparable to previously published studies. As may be expected, heavily pretreated patients had a higher incidence of FN (6% vs. 16%) than those who had received 1 or no previous treatments and may warrant growth factor support. Disclosures:Tombleson:Cephalon: Research Funding. Off Label Use: Bendamustine used for the treatment of myeloma. Ho:Cephalon: Consultancy, Research Funding. Pinilla-Ibarz:Cephalon: Speakers Bureau. Wetzstein:Cephalon: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Prevention of Chemotherapy-Induced Febrile Neutropenia by Prophylactic Antibiotics Plus or Minus Granulocyte Colony-Stimulating Factor in Small-Cell Lung Cancer: A Dutch Randomized Phase III Study

Febrile neutropenia (FN) is a major complication of chemotherapy. Antibiotics as well as granulocyte colony-stimulating factor (G-CSF) are effective in preventing FN. This multicenter randomized phase III trial determines whether the addition of G-CSF to antibiotic prophylaxis can further reduce the incidence of FN in patients with small-cell lung cancer (SCLC) at the risk of FN. Patients (N = 175) were stratified for stage of disease, performance status, age, and prior chemotherapy treatment, and were randomly assigned for treatment with cyclophosphamide, doxorubicin, and etoposide (CDE), followed by prophylactic antibiotics alone (ciprofloxacin and roxithromycin) or by antibiotics in combination with G-CSF on days 4 to 13. In cycle 1, 20 patients (24%) in the antibiotics group developed FN compared with nine patients (10%) in the antibiotics plus G-CSF group (P = .01). In cycles 2 to 5, the incidences of FN were practically the same in both groups (17% v 11%). Only the treatment parameters (odds ratio, 0.33; 95% CI, 0.14 to 0.78) and age (1.067 per year; 95% CI, 1.013 to 1.0124) were related to the probability of FN in cycle 1. Primary G-CSF prophylaxis added to primary antibiotic prophylaxis is effective in reducing FN and infections in SCLC patients at the risk of FN with the first cycle of CDE chemotherapy. For patients with similar risk of FN, the combined use of prophylactic antibiotics plus G-CSF can be considered, specifically in the first cycle of chemotherapy.