Overall Risk Of Febrile Neutropenia Research Articles

Predictive Model for Occurrence of Febrile Neutropenia after Chemotherapy in Patients with Diffuse Large B-Cell Lymphoma: A Multicenter, Retrospective, Observational Study.

Febrile neutropenia (FN) is a major concern in patients undergoing chemotherapy for diffuse large B-cell lymphoma (DLBCL); however, the overall risk of FN is difficult to assess. This study aimed to develop a model for predicting the occurrence of FN in patients with DLBCL. In this multicenter, retrospective, observational analysis, a multivariate logistic regression model was used to analyze the association between FN incidence and pretreatment clinical factors. We included adult inpatients and outpatients (aged ≥ 18 years) diagnosed with DLBCL who were treated with chemotherapy. The study examined 246 patients. Considering FN occurring during the first cycle of chemotherapy as the primary outcome, a predictive model with a total score of 5 points was constructed as follows: 1 point each for a positive hepatitis panel, extranodal involvement, and a high level of soluble interleukin-2 receptor and 2 points for lymphopenia. The area under the receiver operating characteristic curve of this model was 0.844 (95% confidence interval: 0.777-0.911). Our predictive model can assess the risk of FN before patients with DLBCL start chemotherapy, leading to better outcomes.

Prospective study of a web-mediated management of febrile neutropenia related to chemotherapy (Bioconnect)

We aimed to investigate whether patient self-evaluated symptoms transmitted via Internet is feasible between planned visits to provide an early management of fever and neutropenia induced by chemotherapy, and if it can reduce hospitalizations for severe neutropenia. Patients who received a chemotherapy regimen with an overall risk of febrile neutropenia ≥ 20% had to report daily temperature between physician planned visits using a web application. Fever and clinical signs of seriousness were reported to the physician (if some criteria were fulfilled in a specific algorithm) via automatic email notifications by the web application. Patients could be hospitalized quickly or could take over at home, make blood count, and take predefined oral antibiotics if indicated. Primary outcome was patient's compliance and satisfaction. The number and the cost of hospitalization were also assessed and compared with an historical cohort of patients with similar clinical conditions and treatment. Among the 41 patients included, 36 (87.8%) used the web application with 88% of daily compliance and 90% (28/33) of satisfaction. One patient (2.7%) had planned hospitalization after the web application alert. In the historical cohort, the rate of unplanned hospitalization for febrile neutropenia was 17% (6 patients) and 2.7% (1 patient) in users of the web application cohort. The cumulative cost of hospitalization for neutropenia was USD 28,827 in the historical cohort and USD 6563 in the web application cohort. Web-mediated follow-up of febrile neutropenia is feasible. It led to high patient satisfaction, high compliance, and a possible reduction of the number and the cost of hospitalizations.

Prophylactic use of Granulocyte-colony stimulating factors (G-CSF) in cancer patients: Adherence to NCCN guidelines.

209 Background: G-CSF are used for prophylactic and therapeutic treatment of febrile neutropenia (FN). NCCN guidelines (version 1.2015) recommend prophylactic use of G-CSF based on the chemotherapy regimen and patient related risk factors, especially for the high (> 20%) and intermediate (10-20%) risk groups for developing FN. This study investigates the practice patterns and adherence to NCCN guidelines for use of G-CSF at a community based academic outpatient facility. Methods: Cleveland Clinic IRB was obtained. Charts of all patients with underlying non-small cell lung cancer, small cell lung cancer, and breast cancer, treated in the year 2013, were reviewed for G-CSF use on their initial chemotherapy encounter. Risk assessment for developing FN was assessed based on individual risk factors and chemotherapy regimen. Analysis was obtained for appropriate guideline based use of G-CSF. Results: A total of 172 (n = 172) patients were included in the study. Overall, 63% (108/172) of patients had breast cancer; 81% (140/172) were female, most patients (64%, 108/170) were aged < 65 years; 29% (49/172) had metastatic disease; and almost all patients (91%, 106/117) had good ECOG performance status (0 or 1). The overall risk of FN was estimated to be low (< 10%) for 9% (16/172) of patients, intermediate (10-20%) for 45% (77/172) of patients, and high (> 20%) for 45%. Overall, 5% (8/172) of patients did not follow the NCCN guidelines. Only 86% of the patients in metastatic group were adherent to NCCN guidelines compared to 99% of patients in non-metastatic group (p< .01). Among patients with metastatic disease, 14% (7/49) did not follow NCCN guidelines; in a univariable analysis, among patients with metastatic disease - risk of neutropenia (p < .0001), age (p < .01), and prior chemotherapy and or radiation (p = .04), were associated with whether or not the NCCN guidelines were followed. Conclusions: In our limited study population, more use of G-CSF was seen among patients with metastatic cancer with a higher number of metastatic patients being non-adherent to NCCN guidelines. Further research is required to elucidate the potential benefit and cost-effectiveness of G-CSF use in the palliative setting.

Results of a prospective dose intensity and neutropenia prophylaxis evaluation programme (DIEPP) in cancer patients at risk of febrile neutropenia due to myelosuppressive chemotherapy.

SummaryObjectiveTo describe the incidence of febrile neutropenia (FN) and use of pegfilgrastim in cancer patients with high overall risk of FN and to investigate the relationship between granulocyte-colony stimulating factor (G-CSF) guideline adherence and chemotherapy delivery in Central and Eastern Europe (CEE) and Austria.MethodsDose Intensity Evaluation Program and Prophylaxis (DIEPP) was a multicentre, prospective, and observational study of adult patients with breast cancer, lymphoma, lung cancer, gastric cancer, and ovarian cancer, who received chemotherapy with pegfilgrastim support and who had an overall risk of FN ≥ 20 %. Physicians assessed patient risk factors and reported their reasons for administering pegfilgrastim.ResultsPatients were enrolled from 113 centres in CEE and Austria between August 2010 and July 2013, and data were analysed from 1072 patients. The most common tumour types were breast cancer (50 %) and lymphoma (24 %). FN incidence was 5 % overall. FN occurred in 3 % of patients (28/875) who received pegfilgrastim as primary prophylaxis (PP) and 13 % of patients (19/142) who received it as secondary prophylaxis (SP); 79 % of FN events in SP patients occurred in the first cycle before pegfilgrastim was administered. The three most frequently chosen reasons for using pegfilgrastim were planned chemotherapy with high FN risk, female gender, and advanced disease. Overall, 40 % of patients received > 90 % of their planned chemotherapy dose within 3 days of the planned schedule.ConclusionFN incidence was relatively low with pegfilgrastim PP in patients with a physician-assessed overall FN risk of ≥ 20 %. The most important reasons for pegfilgrastim use were consistent with the investigators’ risk assessment and international guidelines.

Neutropenia management and granulocyte colony-stimulating factor use in patients with solid tumours receiving myelotoxic chemotherapy—findings from clinical practice

PurposeClinical practice adherence to current guidelines that recommend primary prophylaxis (PP) with granulocyte colony-stimulating factors (G-CSFs) for patients at high (≥20 %) overall risk of febrile neutropenia (FN) was evaluated.MethodsAdult patients with breast cancer, non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), or ovarian cancer were enrolled if myelotoxic chemotherapy was planned, and they had an investigator-assessed overall FN risk ≥20 %. The primary outcome was FN incidence.ResultsIn total, 1,347 patients were analysed (breast cancer, n = 829; NSCLC, n = 224; SCLC, n = 137; ovarian cancer, n = 157). Patients with breast cancer exhibited fewer individual FN risk factors than patients with other cancers and were far more likely to have received a high-FN-risk chemotherapy regimen. However, a substantial proportion of all patients (45–80 % across tumour types) did not receive G-CSF PP in alignment with investigator risk assessment and guideline recommendations. FN occurred in 127 patients overall (9 %, 95% confidence interval (CI) 8–11 %), and incidence was higher in SCLC (15 %) than other tumour types (8 % in ovarian and NSCLC, 9 % in breast cancer). A post hoc analysis of G-CSF use indicated that G-CSF prophylaxis was not given within the recommended timeframe after chemotherapy (within 1–3 days) or was not continued across all cycles in 39 % of patients.ConclusionsFN risk assessment was predominantly based on clinical judgement and individual risk factors, and guidelines regarding G-CSF PP for patients at high FN risk were not consistently followed. Improved education of physicians may enable more fully informed neutropenia management in patients with solid tumours.Electronic supplementary materialThe online version of this article (doi:10.1007/s00520-013-2021-2) contains supplementary material, which is available to authorized users.

Is primary prophylaxis with granulocyte colony stimulating factor (G-CSF) indicated in the treatment of lymphoma?

Febrile neutropenia (FN) is a common complication of cancer therapy. It can contribute to delays in treatment, increased rates of hospitalization, and severe infections. FN may also hinder completion of intended chemotherapy. Granulocyte colony stimulating factors (G-CSF) lower the rates of FN, infections, and hospitalization. Multiple national and international guidelines advocate the use of G-CSF in primary prophylaxis if the overall risk of FN is >20% (accounting for both patient and treatment-related risks). Lymphoma specific guidelines recommend G-CSF use in similar fashion. However, based on our updated review of published literature, we note that primary prophylaxis (PP) with G-CSF fails to improve overall survival as well as infection-related mortality. Moreover, lymphoma specific cost-effectiveness analyses on the use of PP have shed further doubt on the optimal use of this myeloid growth factor. In this general review, we will discuss whether PP with GCSF has any role in the management of adults with non-Hodgkin lymphoma.

Abstract P1-15-04: The relationship of relative dose intensity and supportive care to febrile neutropenia rates in patients with early stage breast cancer receiving chemotherapy: a prospective cohort study of chemotherapy-associated toxicity

Abstract Background: Febrile neutropenia (FN) represents a major dose-limiting toxicity of cancer chemotherapy resulting in considerable morbidity, mortality, and cost. Patients have the highest risk of the initial neutropenic event in cycle 1 when most patients receive full dose chemotherapy. This study evaluates time course of neutropenic events in patients receiving chemotherapy for early-stage breast cancer (ESBC) and supportive care interventions that modify FN risk in ESBC patients treated in actual oncology practice. Methods: A prospective cohort study of adult cancer patients with solid tumors or lymphoma starting a chemotherapy regimen was conducted at 115 U.S. sites. Toxicities associated with chemotherapy were recorded in up to 4 cycles including severe neutropenia (SN), FN, and infection. Documented clinical interventions included reductions in chemotherapy relative dose intensity (RDI), the use of colony-stimulating factors (CSFs), and antibiotics. Results: A total of 1202 ESBC patients starting chemotherapy were analyzed, of which 1154, 1099, and 896 reached the midcycle of cycles 2, 3, and 4, respectively. While the majority of neutropenic and infection events occurred in cycle 1, decreasing rates of FN and infection in later cycles correlated with increasing reductions in dose intensity and increased use of CSFs and antibiotics. The overall risk of FN in all patients combined was 16.3 %. It reached 21.1% for patients who started with planned RDI≥85% and without primary CSF prophylaxis. There was no significant difference in FN rates by menopausal status or hormone receptors. Conclusions: While the risk of neutropenic complications is highest during the first cycle of chemotherapy, reductions in neutropenic events during subsequent cycles are associated with reduced chemotherapy dose intensity or increased use of supportive care measures. Nevertheless, the cumulative risk of neutropenic events remains high in ESBC patients receiving full dose chemotherapy without prophylactic measures overall and across menopausal and hormone receptor subgroups. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-15-04.

1560P - The Neutropenia Prophylaxis Evaluation Program in Patients Receiving Myelosuppressive Chemotherapy with Moderate or High Risk of Febrile Netropenia – an Interim Analysis of the Diepp Study

ABSTRACT Background Pegfilgrastim is a pegylated granulocyte colony stimulating factor (G-CSF) indicated for the prophylaxis of febrile neutropenia (FN) in patients (pts) treated with myelosuppressive chemotherapy (CT). The DIEPP study was designed to evaluate FN incidence and risk assessment in pts at high overall risk of FN receiving myelosuppressive CT with pegfilgrastim prophylaxis. Methods This prospective observational study collected data from pts within Central and Eastern Europe and Austria having the following malignancies: early stage breast cancer (stages I-III), diffuse large B-cell lymphoma, lung, gastric or ovarian cancer. To be eligible, pts had an investigator-assessed overall risk of FN ≥20% (CT plus patient risk factors), and were planned to receive pegfilgrastim according to the SmPC and to receive CT for ≥4 cycles. The primary objective was to estimate FN incidence and secondary objectives included assessment of which risk factors (RF) from the ASCO/EORTC guidelines most often contributed to the decision to use pegfilgrastim primary (PP) or secondary (SP) prophylaxis. The final planned sample size is 1,200 pts; this interim analysis includes data collected from the Czech Republic, Poland, Hungary, Romania, and Austria between 08/2011 and 01/2012. Results At the interim cut off time 268 enrolled pts (mean age 58 ± 12 years, 25% male) received 1343 CT cycles; 237 pts (88%) received PP, 10 pts (4%) SP, and 21 pts (8%) delayed or other pegfilgrastim administration. Overall 9 pts (4%; 95% CI [2%, 6%]) reported FN in a total of 10 (1%; 95% CI [0.4%, 1%]) cycles. Five pts (2%; 95% CI [1%, 4%]) reported FN in the first CT cycle. The high FN risk of planned CT was the most common reason reported by physicians for pegfilgrastim use: 80% pts [95% CI [74%, 84%]. The three most common pt-related RFs were: female gender, 54%, 95% CI [48, 60]; advanced disease stage, 41%, 95% CI [35%, 47%]; and age ≥65, 21% 95% CI [17%, 27%]. No SADR and 2 ADR cases (neutropenia and bone pain) were registered. Conclusion Based on data from the CEE and Austria, rates of FN were low with pegfilgrastim prophylaxis in pts receiving CT with an overall FN risk of ≥20%. Disclosure T. Csoszi: corporate-sponsored study - VECTIS, DIEPP, D-CARE( Amgen20060359, APPRIORI,Amgen 20080259, M. Safanda: corporate-sponsored study - DIEPP (Amgen), G. Mazur: corporate-sponsored study - DIEPP (Amgen) G. Mihaylov: corporate-sponsored study - DIEPP (Amgen), J. Benkovicova: corporate-sponsored study - DIEPP (Amgen), E. Toth: Amgen contract worker.

2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours

Chemotherapy-induced neutropenia is a major risk factor for infection-related morbidity and mortality and also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact the success of treatment, particularly when treatment intent is either curative or to prolong survival. In Europe, prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim (including approved biosimilars), lenograstim or pegfilgrastim is available to reduce the risk of chemotherapy-induced neutropenia. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. The need for generally applicable, European-focused guidelines led to the formation of a European Guidelines Working Party by the European Organisation for Research and Treatment of Cancer (EORTC) and the publication in 2006 of guidelines for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. A new systematic literature review has been undertaken to ensure that recommendations are current and provide guidance on clinical practice in Europe. We recommend that patient-related adverse risk factors, such as elderly age (⩾65 years) and neutrophil count be evaluated in the overall assessment of FN risk before administering each cycle of chemotherapy. It is important that after a previous episode of FN, patients receive prophylactic administration of G-CSF in subsequent cycles. We provide an expanded list of common chemotherapy regimens considered to have a high (⩾20%) or intermediate (10–20%) risk of FN. Prophylactic G-CSF continues to be recommended in patients receiving a chemotherapy regimen with high risk of FN. When using a chemotherapy regimen associated with FN in 10–20% of patients, particular attention should be given to patient-related risk factors that may increase the overall risk of FN. In situations where dose-dense or dose-intense chemotherapy strategies have survival benefits, prophylactic G-CSF support is recommended. Similarly, if reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis, primary G-CSF prophylaxis may be used to maintain chemotherapy. Clinical evidence shows that filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications where indicated. Filgrastim biosimilars are also approved for use in Europe. While other forms of G-CSF, including biosimilars, are administered by a course of daily injections, pegfilgrastim allows once-per-cycle administration. Choice of formulation remains a matter for individual clinical judgement. Evidence from multiple low level studies derived from audit data and clinical practice suggests that some patients receive suboptimal daily G-CSFs; the use of pegfilgrastim may avoid this problem.

Prophylaxis of chemotherapy-induced febrile neutropenia with granulocyte colony-stimulating factors: where are we now?

Updated international guidelines published in 2006 have broadened the scope for the use of granulocyte colony-stimulating factor (G-CSF) in supporting delivery of myelosuppressive chemotherapy. G-CSF prophylaxis is now recommended when the overall risk of febrile neutropenia (FN) due to regimen and individual patient factors is ≥20%, for supporting dose-dense and dose-intense chemotherapy and to help maintain dose density where dose reductions have been shown to compromise outcomes. Indeed, there is now a large body of evidence for the efficacy of G-CSFs in supporting dose-dense chemotherapy. Predictive tools that can help target those patients who are most at risk of FN are now becoming available. Recent analyses have shown that, by reducing the risk of FN and chemotherapy dose delays and reductions, G-CSF prophylaxis can potentially enhance survival benefits in patients receiving chemotherapy in curative settings. Accumulating data from ‘real-world’ clinical practice settings indicate that patients often receive abbreviated courses of daily G-CSF and consequently obtain a reduced level of FN protection. A single dose of PEGylated G-CSF (pegfilgrastim) may provide a more effective, as well as a more convenient, alternative to daily G-CSF. Prospective studies are needed to validate the importance of delivering the full dose intensity of standard chemotherapy regimens, with G-CSF support where appropriate, across a range of settings. These studies should also incorporate prospective evaluation of risk stratification for neutropenia and its complications.

Febrile Neutropenia Risk Assessment and Granulocyte-Colony Stimulating Factor Support in Patients with Diffuse Large B Cell Lymphoma Receiving R-CHOP Regimens.

Abstract 107 BACKGROUND:ASCO and EORTC guidelines recommend granulocyte colony-stimulating factor (G-CSF) primary prophylaxis for cancer patients with a ≥20% overall risk of febrile neutropenia (FN), and to support delivery of dose-dense regimens. CHOP-like regimens (with rituximab [R]) are the current standard of care for the management of aggressive non-Hodgkin lymphoma (NHL), but they are often associated with significant myelosuppression. Neutropenic events, particularly febrile neutropenia (FN), can be life-threatening and may lead to dose delays or reductions that compromise the efficacy of chemotherapy. In IMPACT NHL, we evaluated current practice in FN risk assessment and use of G-CSF prophylaxis in patients receiving (R)CHOP. METHODS: IMPACT NHL is a retrospective and prospective observational study conducted in 14 European countries and Australia. Physicians assessed the overall FN risk of NHL patients and their need for G-CSF prophylaxis. This analysis focuses on patients with diffuse large B-cell lymphoma (DLBCL) receiving either 2-weekly R-CHOP-14 or 3-weekly R-CHOP-21. FN risk was assessed according to EORTC guidelines (i.e. the total risk from the chemotherapy regimen plus individual patient risk factors). The primary outcome measure was the proportion of patients assessed as being at ≥20% risk of FN and who were planned to receive primary prophylaxis with a G-CSF (defined as G-CSF initiation within days 1-7 of cycle 1). RESULTS: Data were available for 1829 patients who initiated chemotherapy between 01/2005 and 08/2008; 1136 had DLBCL. The mean age±SD of patients receiving R-CHOP-21 (N=704) was 62.6±13.8 years, 51% were aged ≥65 years and 53% had Stage III-IV disease. For R-CHOP-14 patients (N=409), the mean age was 58.4±14.7 years, 41% were ≥65 years and 59% had Stage III-IV disease. In total, 434 R-CHOP-21 patients were assessed as being at high risk for FN and 47% of them actually received G-CSF primary prophylaxis (with either pegfilgrastim or daily G-CSF) (see Table). Furthermore, almost a fifth of patients assessed as being at <20% FN risk received G-CSF primary prophylaxis. Across all cycles, 29% of R-CHOP-21 patients had an unplanned hospitalization, with neutropenia/FN being the main reason. Subsequently, 67% of patients achieved a relative dose intensity (RDI) of ≥90% of their planned treatment (with respect to cyclophosphamide, doxorubicin, and vincristine). In the R-CHOP-14 group, 16% of patients did not receive G-CSF primary prophylaxis; 32% had an unplanned hospitalization and 59% of patients achieved '90% of their planned RDI.TableFN risk assessment, G-CSF support and FN outcomes in patients receiving R-CHOP-21 or R-CHOP-14R-CHOP-21R-CHOP-14Overall FN risk assessment≥20%<20%N/AN434266409G-CSF PP recommended per guidelinesYesNoYes (dose dense)G-CSF PP planned237 (55%)46 (17%)348 (85%)G-CSF PP given205 (47%)47 (18%)345 (84%)FN* in any cycle89 (21%)43 (16%)81 (20%)FN* in cycle 145 (10%)17 (6%)24 (6%)RCHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, prednisonePP: primary prophylaxis*FN defined as absolute neutrophil count <0.5 × 109/L (or <1.0 × 109/L and predicted to fall <0.5) and fever CONCLUSIONS:Half of R-CHOP-21 patients assessed as high risk for FN did not receive G-CSF primary prophylaxis despite physicians' awareness of elevated risk, while primary G-CSF support was not given to almost one fifth of R-CHOP-14 patients, contrary to guideline recommendations. Both R-CHOP-14 and R-CHOP-21 resulted in significant myelotoxicity (with substantial FN even in those evaluated as being at lower risk), and only around two-thirds of patients received optimal chemotherapy RDI. Our data suggest that improvements in neutropenia management are required. More consistent use of G-CSF primary prophylaxis may further reduce FN and assist in optimal chemotherapy delivery.Sponsored by Amgen Disclosures:Salar:Amgen: Honoraria. Haioun:Roche: Research Funding; Amgen: Other, Research Funding; Celgene: Other, Research Funding; Mundipharma: Research Funding. Pettengell:Amgen: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau; Bayer: Honoraria, Speakers Bureau. Jaeger:Amgen: Research Funding. Schwenkglenks:Amgen: Honoraria, Research Funding. Bacon:Amgen: Employment, Equity Ownership. Bendall:Amgen: Employment.

The economic value of primary prophylaxis using pegfilgrastim compared with filgrastim in patients with breast cancer in the UK

Febrile neutropenia (FN) is a serious adverse event associated with myelotoxic chemotherapy that predisposes patients to life-threatening bacterial infections. Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) from the first cycle of chemotherapy is recommended by the 2006 American Society of Clinical Oncology, 2008 National Comprehensive Cancer Network and 2006 European Organisation for Research and Treatment of Cancer guidelines when the overall risk of FN is approximately 20% or higher. Once-per-cycle pegfilgrastim and daily filgrastim are two commonly used G-CSFs with different dosing schedules and associated costs. To evaluate the cost effectiveness of pegfilgrastim versus filgrastim primary prophylaxis in women with early-stage breast cancer receiving chemotherapy in the UK. A decision-analytic model was constructed from the UK NHS perspective with a lifetime study horizon. The model simulated three clinical scenarios: scenario 1 assumed that pegfilgrastim and filgrastim had differential impact on the risk of FN; scenario 2 assumed additional differential impact on FN-related mortality; and scenario 3 assumed additional differential impact on chemotherapy relative dose intensity (RDI) with long-term survival effects. The base-case population included 45-year-old women with stage II breast cancer receiving four chemotherapy cycles, with an FN risk of approximately 20% or higher. Model inputs, including FN risk, FN case-fatality, RDI, impact of RDI on survival and utility scores, were based on a review of the literature and expert panel validation. Using data from the literature, it was estimated that the absolute risk of FN associated with pegfilgrastim was 5.5% lower than with 11-day filgrastim (7% vs 12.5%), and 10.5% lower than with 6-day filgrastim (7% vs 17.5%). Costs were taken from official price lists or the literature and included drugs, drug administration, FN-related hospitalizations and subsequent medical costs. Breast cancer mortality and all-cause mortality were obtained from official statistics. The main outcome measures were the costs ( pound, year 2006 values) per percentage decrease in (absolute) FN risk, per FN event avoided, per life-year gained (LYG), and per QALY gained. Model robustness was tested using deterministic and probabilistic sensitivity analyses. Pegfilgrastim was cost saving compared with 11-day filgrastim ( pound 3196 vs pound 4315). Compared with 6-day filgrastim, pegfilgrastim was associated with a cost of pound 4200 per FN event avoided, or pound 42 per 1% decrease in absolute risk of FN, in scenario 1. In scenario 2, pegfilgrastim provided 0.055 more LYGs or 0.052 more QALYs at a minimal cost increase of pound 441 ( pound 3196 vs pound 2754) per person, yielding an incremental cost-effectiveness ratio (ICER) of pound 8075/LYG or pound 8526/QALY. In scenario 3, when all potential benefits of G-CSF were considered, the ICER became pound 3955/LYG or pound 4161/QALY. Results were most sensitive to the relative risk of FN for 6-day filgrastim versus pegfilgrastim. In this UK analysis, pegfilgrastim appears to dominate 11-day use of filgrastim. The value of pegfilgrastim versus 6-day filgrastim at pound 4161-8526/QALY was very favourable compared with the commonly used threshold in the UK. In this setting, primary prophylaxis with pegfilgrastim may be cost effective compared with filgrastim.

A Prospective Multivariate Analysis of Risk Factors Associated with Occurrence of Febrile Neutropenia in Any Cycle in NHL Patients Receiving Chemotherapy.

Febrile neutropenia (FN) following chemotherapy often results in hospitalisation and chemotherapy dose delays or reductions in subsequent cycles. Although current guidelines highlight non-Hodgkin lymphoma (NHL) patients receiving standard regimens as having a significant risk of FN, the contribution of additional factors to the overall risk of FN is not fully understood. We present a logistic regression model describing the relationship of various clinical factors with FN occurrence in NHL. Predictors were chosen based on their clinical and statistical significance (5% level) and to allow comparison with other models. Data were obtained from the INC-EU Prospective Observational European Neutropenia Study, which aimed to assess the incidence and predictors of neutropenia, FN and chemotherapy dose limitations in breast cancer and lymphoma. 240 NHL patients were recruited from 37 centres in Belgium, France, Germany, Spain, and the UK. Ann Arbor stages were distributed: I 18%; II 26%; III 17%; IV 40%. Chemotherapy regimens received were 3-weekly CHOP-like (74%), 2-weekly CHOP-like (17%), ACVBP-like (4%) and other regimens (5%). Overall colony stimulating factor (CSF) prophylaxis in patients who had not previously experienced FN was 50%. FN incidence in any cycle was 22%. The resulting logistic regression model of any FN occurrence is shown in the table. Replacing GFR and height with the closely related parameters of age and weight slightly affected predictive ability but did not affect model stability. The area under the receiver operating characteristic curve was 0.84. Using the optimal probability cut-off, model test characteristics were 75% sensitivity and 76% specificity; corresponding to positive and negative predictive values of 48% and 91%, respectively. Low absolute neutrophil or white blood cell count (ANC, WBC), high baseline alkaline phosphatase, low GFR (or high age), low height (or low weight), cardiac comorbidity, recent infection, and high planned chemotherapy dose appeared to increase the risk of FN occurrence. Although chemotherapy dose reduction or delay protected against FN, these are associated with reduced survival in patients receiving CHOP-like regimens. CSF use was a protective factor. These results complement risk factors highlighted in current guidelines. [Display omitted]

Use of Colony-Stimulating Factors for Chemotherapy-Associated Neutropenia: Review of Current Guidelines

Chemotherapy-associated neutropenia is often dose-limiting and may compromise treatment efficacy. Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage-colony-stimulating factor (GM-CSF) are increasingly used to prevent febrile neutropenia (FN) or to increase dose-density. This review discusses recent changes in treatment guidelines for chemotherapy-associated neutropenia. Primary prophylactic use of CSFs is now recommended as a treatment option at an overall risk of FN of 20%, not taking into account cost-effectiveness. To estimate the risk of FN, patient-, disease-, and treatment-related factors predicting an adverse outcome of FN have been determined. Dose-dense chemotherapy has become feasible with the use of CSFs. However, clinical benefit has been shown only for specific chemotherapy regimens in breast cancer, small cell lung cancer (SCLC), and non-Hodgkin's lymphoma (NHL), for the latter particularly for patients above 60 years of age. Strategies are being developed to tailor the use of CSFs to patients with a high risk of adverse outcome of FN.

EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphomas and solid tumours

Chemotherapy-induced neutropenia is not only a major risk factor for infection-related morbidity and mortality, but is also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact on the success of treatment, particularly when treatment intent is either curative or to prolong survival. The incidence of severe or FN can be reduced by prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim, lenograstim or pegfilgrastim. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. While several academic groups have produced evidence-based clinical practice guidelines in an effort to standardise and optimise the management of FN, there remains a need for generally applicable, European-focused guidelines. To this end, we undertook a systematic literature review and formulated recommendations for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. We recommend that patient-related adverse risk factors such as elderly age (⩾65 years), be evaluated in the overall assessment of FN risk prior to administering each cycle of chemotherapy. In addition, when using a chemotherapy regimen associated with FN in >20% patients, prophylactic G-CSF is recommended. When using a chemotherapy regimen associated with FN in 10–20% patients, particular attention should be given to patient-related risk factors that may increase the overall risk of FN. In situations where dose-dense or dose-intense chemotherapy strategies have survival benefits, prophylactic G-CSF support is recommended. Similarly, if reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis, primary G-CSF prophylaxis may be used to maintain chemotherapy. Finally, studies have shown that filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications, where indicated.