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Background/aim: We evaluated the long-term outcome of docetaxel, cisplatin, and 5-fluorouracil as combination chemoradiotherapy (DCF-RT) for patients with potentially resectable esophageal cancer (EC) in clinical settings., Patients and Methods: Twenty-eight patients with potentially resectable thoracic EC were included in this study. Chemotherapy consisted of intravenous docetaxel at 50 mg/m 2 (day 1), CDDP at 60 mg/m 2 (day 1), and 5-FU at 600 mg/m 2 (days 1 to 4), repeated every four weeks for two cycles along with radiotherapy (60 Gy in 30 fractions). Potentially resectable esophageal cancer was defined as clinical stage (cStage) I, II, III, and IV with supraclavicular lymph node metastasis [M1(Lym)]., Results: The overall complete response (CR) rate was 88.5%. The 5-year overall survival (OS) rates for cStage I, cStage II-III, and IV [M1(lym)] patients were 79.5%, 76.2%, and 50.0%, respectively. The most frequent grade 3 or 4 acute toxicities were leucopenia (85.7%), neutropenia (78.5%), and febrile neutropenia (FN) (21.4%). The rate of any grade 3 or 4 late toxicity was 7.7%., Conclusion: DCF-RT demonstrated a satisfactory CR rate and OS with a higher rate of FN for potentially resectable thoracic EC patients. Prophylactic treatment with granulocyte-colony-stimulating factor and antibiotics may be appropriate supportive care for patients undergoing DCF-RT., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Describe temporal changes in use of myelosuppressive chemotherapy, primary prophylactic colony-stimulating factor, and neutropenia-related hospitalization, in commercially insured patients., Methods: Using a large commercial administrative database, we identified annual cohorts of adult patients diagnosed with breast or lung cancer, or non-Hodgkin lymphoma and initiating myelosuppressive chemotherapy during 2005-2017. We described yearly changes in proportions of myelosuppressive chemotherapy by febrile neutropenia risk category (high, intermediate, unclassified) and proportion of prophylactic colony-stimulating factor use and unadjusted incidence of neutropenia-related hospitalization in the first cycle of myelosuppressive chemotherapy., Results: Annual cohorts included 4383-5888 eligible patients during 2005-2017. The proportion of eligible patients aged ≥ 65 years increased from 26.0% in 2005 to 58.2% in 2017. Myelosuppressive chemotherapy use with regimens with high risk for febrile neutropenia increased from 15.1% in 2005 to 31.0% in 2017; and regimens with intermediate risk for febrile neutropenia decreased from 63.7% to 48.1% in 2017. Prophylactic colony-stimulating factor use increased from 41.6% in 2005 to 54.3% in 2017. Crude incidence of neutropenia-related hospitalization for all cancers increased from 2.0% to 3.1%, with a substantial increase in neutropenia-related hospitalization observed among non-Hodgkin lymphoma patients (2.8% to 8.5%) during 2005-2017., Conclusion: Among adult patients with breast and lung cancer, and non-Hodgkin lymphoma receiving myelosuppressive chemotherapy, use of regimens with high risk for febrile neutropenia increased, as did the use of prophylactic colony-stimulating factors after 2005. Incidence of neutropenia-related hospitalization increased slightly, particularly among non-Hodgkin lymphoma patients. Further studies are required to understand this increasing trend of neutropenia-related hospitalization, changing patient-level risk factors, and febrile neutropenia management.

Introduction: The administration of myeloid growth factors is the only approved treatment for the prevention of chemotherapy induced neutropenia and febrile neutropenia. However, their specific indications and contraindications and potential side effects limit their application to only a relatively small subset of patients at the highest risk for complications, such as infection., Areas Covered: A computerized systematic literature search was performed through Medline, Google Scholar, Cochrane Library, the Pharmaprojects database and the clinicaltrials.gov website. The shortcomings of the existing treatment approach are reviewed, along with a synopsis of the characteristics of novel agents that protect bone marrow progenitors from the cytotoxic effects of antineoplastic treatment that may be used in the future as a stand-alone preventive strategy or as an adjunct to growth factors., Expert Opinion: There is an abundance of agents undergoing evaluation for the prevention of treatment-induced neutropenia. The appropriate selection of patients, the optimization of the use of existing agents and the increasing competition from biosimilars which likely ensure future decreases in healthcare costs are essential for growth factors to retain their dominant position in this setting.

Background: Healthcare claims databases have been used in several studies to characterize the risk and burden of chemotherapy-induced febrile neutropenia (FN) and effectiveness of colony-stimulating factors against FN. The accuracy of methods previously used to identify FN in such databases has not been formally evaluated., Methods: Data comprised linked electronic medical records from Geisinger Health System and healthcare claims data from Geisinger Health Plan. Subjects were classified into subgroups based on whether or not they were hospitalized for FN per the presumptive "gold standard" (ANC <1.0×10(9)/L, and body temperature ≥38.3°C or receipt of antibiotics) and claims-based definition (diagnosis codes for neutropenia, fever, and/or infection). Accuracy was evaluated principally based on positive predictive value (PPV) and sensitivity., Results: Among 357 study subjects, 82 (23%) met the gold standard for hospitalized FN. For the claims-based definition including diagnosis codes for neutropenia plus fever in any position (n=28), PPV was 100% and sensitivity was 34% (95% CI: 24-45). For the definition including neutropenia in the primary position (n=54), PPV was 87% (78-95) and sensitivity was 57% (46-68). For the definition including neutropenia in any position (n=71), PPV was 77% (68-87) and sensitivity was 67% (56-77)., Conclusions: Patients hospitalized for chemotherapy-induced FN can be identified in healthcare claims databases--with an acceptable level of mis-classification--using diagnosis codes for neutropenia, or neutropenia plus fever.

Fever occurs at high rates in patients with chemotherapy-induced neutropenia and is considered an oncologic emergency. Numerous algorithms have been developed to guide treatment decisions. Prompt care and the initiation of empiric antibiotic therapy are critically important universal aspects of these treatment-decision schemata. Fever may be the only sign of infection, as in patients with cancer who are undergoing chemotherapy, the immune response is attenuated. In the majority of cases, no etiology for neutropenic fever is uncovered; nonetheless, a thorough workup is essential. The workup allows practitioners to risk stratify patients as being at low or high risk for infectious complications so that appropriate care can be administered. Although it is important to note that there are management algorithms to follow, every patient may present and respond differently. We generally start with broad-spectrum monotherapy for Gram-negative bacteria and then consider whether Gram-positive or antifungal coverage is necessary based on the clinical picture, including factors such as duration and degree of neutropenia. It is important for all practitioners to understand how to care for patients with neutropenic fever because it is a common and treatable condition.

Neutropenia induced by chemotherapy (CT) is an infection risk factor associated to greater morbidity/mortality and dose-limiting toxicity that on many occasions requires a reduction of the dose of cytostatics or a delay in the administration of treatment. This may have a negative effect on the patient's quality of life and even diminish the efficacy of the treatment, especially when the intention is to cure or prolong survival. Management of treatment or prophylaxis of grade 3-4 neutropenia and febrile neutropenia with myeloid growth factors (CSF) varies very much in clinical practice, both in the time of starting treatment and the types of patients it is given to. The need to generalise and facilitate practice based on clinical evidence has led the Spanish Society of Medical Oncology (SEOM) to prepare clinical practice guidelines on the use of myeloid growth factors.

Study Objective: To determine the impact of primary prophylactic colony-stimulating factor (CSF) use on febrile neutropenia in a large patient population receiving contemporary chemotherapy regimens to treat breast cancer, colorectal cancer, or non-small cell lung cancer (NSCLC)., Design: Retrospective claims analysis., Data Sources: The Surveillance, Epidemiology, and End Results (SEER)-Puget Sound cancer registry and insurance claims records., Patients: A total of 2728 patients aged 25 years or older who received a diagnosis of breast cancer (998 patients), colorectal cancer (688 patients), or NSCLC (1042 patients) between January 1, 2002, and December 31, 2005, and received chemotherapy., Measurements and Main Results: Initial chemotherapy regimen, CSF use (filgrastim or pegfilgrastim), and febrile neutropenia events were evaluated after the first chemotherapy administration. Subsequently, febrile neutropenia rates in patients receiving primary prophylactic CSF were compared with febrile neutropenia rates in patients receiving CSF in settings other than primary prophylaxis or not at all. The impact of primary prophylactic CSF could not be assessed for patients with colorectal cancer or NSCLC because only 1 and 18 febrile neutropenia events, respectively, occurred in those receiving primary prophylactic CSF. Of the 998 patients with breast cancer, 72 (7.2%) experienced febrile neutropenia, 28 of whom received primary prophylactic CSF. In the patients with breast cancer, we observed that primary prophylactic CSF use was associated with reduced febrile neutropenia rates; however, the analysis may have been confounded by unmeasured factors associated with febrile neutropenia., Conclusion: The impact of primary prophylactic CSFs on febrile neutropenia rates could not be demonstrated. Given the substantive cost of CSFs to pharmacy budgets, there are numerous opportunities for pharmacists to optimize CSF use. Research studies are needed to evaluate if guideline-directed prescribing of primary prophylactic CSFs can improve clinical outcomes., (© 2012 Pharmacotherapy Publications, Inc.)

Chemotherapy-induced neutropenia can cause fatal bacterial infections. Colony-stimulating factors (CSFs) are usually recommended as prophylaxis, while routine use of prophylactic antibiotics remains controversial. Based on our literature search in PubMed, quinolones and trimethoprim/sulfamethoxazole were the most frequently used prophylaxis, while CSFs were administered in 22.1% of patients. Lung cancer patients who received prophylactic antibiotics exhibited significantly fewer episodes of febrile neutropenia, fewer documented infections as well as shorter duration of related hospitalisations. Prophylactic use of wide spectrum antibiotics seems effective and should be considered as an alternative strategy in the prevention of chemotherapy-induced neutropenia in lung cancer patients., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Neutropenia poses a serious threat to patients on chemotherapy. It exposes them to the risk of infection--including potentially fatal infections--and also leads to delays in treatment and reductions in dose intensity, which can compromise the possibility of a favorable outcome., Areas Covered: The use of granulocyte colony-stimulating factors (G-CSF) and antibiotics to prevent febrile neutropenia (FN) and to ameliorate cancer chemotherapy-induced myelosuppression is discussed, based on a systematic search of Pubmed for clinical trials, reviews and meta-analysis published in the last 20 years. We consider that the treatment of FN, with the emphasis on careful attention to the patient, prompts antibiotic therapy and good hospital care., Expert Opinion: We would argue that antibiotic prophylaxis should be offered routinely to patients receiving cytotoxic chemotherapy for acute leukemia and for patients with solid tumors and lymphoma receiving high-dose chemotherapy. In patients undergoing cyclical standard-dose myelosuppressive chemotherapy, we believe that prophylaxis is indicated during the first cycle of chemotherapy in which there is an expectation of grade 4 neutropenia (< 500 neutrophils). However, although the use of antibiotics and haematopoietic growth factors may improve quality of life by reducing the risk and consequences of FN, further study of the magnitude of their effects is needed.

Objectives: We examined health care use in conjunction with primary prophylaxis use of colony stimulating factors (CSF) during patients' initial course of chemotherapy., Methods: This retrospective cohort study identified adults aged 25 years and older with a diagnosis of breast, colorectal, or nonsmall cell lung cancer between 2002 and 2005 from the Western Washington Surveillance Epidemiology and End Results Puget Sound registry. We linked these records to health insurance claims from four payers representing 75% of those insured in the state. Claims records were used to determine chemotherapy regimen type, CSF use, febrile neutropenia occurrences, and supportive care. Chemotherapy regimens were categorized as conferring high, intermediate, or low risk of myelosuppression according to the National Comprehensive Cancer Network guidelines. CSF use was described as primary prophylaxis, other, or none. Antibiotics and antifungal and antiviral agents per National Comprehensive Cancer Network guidelines for supportive care for cancer infection were categorized using Healthcare Common Procedure Coding System and National Drug Code assignments., Results: Use of CSF as primary prophylaxis is not significantly associated with a reduction in antibiotic use or inpatient or outpatient visits. Primary prophylactic CSF use was associated with less use of antiviral drugs., Conclusions: CSF use is not associated with a reduction in health care use, with the exception of antiviral drug use. Given the expense associated with CSF use, pragmatic trials and additional research are needed to further assess the affects of CSF on health care use., (Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: Granulocyte colony stimulating factors (G-CSFs) decrease the incidence of febrile neutropenia (FN) in cancer patients receiving myelosuppressive chemotherapy. There are two G-CSFs (pegfilgrastim and filgrastim) that differ in dosing schedules from which oncologists may prescribe., Objectives: This study aimed to compare the effectiveness of prophylactic pegfilgrastim and filgrastim on the risk of hospitalizations. The secondary objective was to compare the effectiveness of the timing of initiation (prophylactic versus delayed)., Methods: A retrospective study of administrative claims from US commercial payers included adult patients with Non-Hodgkin's lymphoma, breast, or lung cancer, treated with chemotherapy between July 2004 and January 2008. For these patients, the first course of chemotherapy and each unique cycle with use of G-CSF was identified and designated 'prophylaxis' if used within the first 5 days of each cycle, or 'delayed', if after day 5. The risk of neutropenia-related and all-cause hospitalization was evaluated for the pegfilgrastim and filgrastim prophylaxis cohorts and for the prophylaxis and delayed G-CSF initiation cohorts., Results: Among 5,571 patient-cycles identified, 88.9% and 11.1% used pegfilgrastim and filgrastim respectively. The rate of neutropenic hospitalization was 1.1% for pegfilgrastim prophylaxis and 3.5% for filgrastim prophylaxis (P = 0.001). Compared to chemotherapy cycles with filgrastim prophylaxis, those with pegfilgrastim prophylaxis had decreased risk of neutropenia-related (adjusted odds ratio (OR) = 0.38, 95% confidence interval (CI) 0.17-0.83) and all-cause hospitalization (adjusted OR = 0.51, 95% CI 0.31-0.84). The neutropenic hospitalization rate was 1.2% for G-CSF prophylactic initiation and 3.7% for delayed G-CSF initiation (P < 0.001). Chemotherapy cycles with prophylactic initiation of either G-CSF had decreased risk of neutropenia-related (adjusted OR = 0.34, 95% CI 0.21-0.56) and all-cause hospitalization (adjusted OR = 0.67, 95% CI 0.49-0.91) compared with delayed initiation of G-CSF., Conclusions: Pegfilgrastim prescribed as prophylaxis resulted in lower risk of neutropenia-related and all-cause hospitalizations compared to filgrastim prophylaxis. This reduction was similar for prophylactic G-CSF initiation when compared to delayed G-CSF initiation.

Chemotherapy-induced neutropenia and its complications are major dose-limiting toxicities of cancer chemotherapy. The myeloid growth factors have been shown to reduce the risk of neutropenic events across malignancies, regimens, and associated risk categories often enabling the delivery of greater chemotherapy dose intensity. Three different practice guidelines for the myeloid growth factors have recently been published by major professional organizations. A comprehensive review and comparison of the guidelines using a priori structured content criteria and a previously validated quality appraisal tool are reported. Consistency in the final recommendations from these guidelines is observed for primary prophylaxis with the colony-stimulating factors (CSFs) when the risk of febrile neutropenia is in the range of 20% or greater. There is also consistency in the recommendation that patients receiving regimens associated with lower risk should have CSF use guided by individual risk assessment. Critical quality appraisal indicates that the scope and purpose, stakeholder involvement, and applicability of the guidelines differ little. There is more emphasis on comprehensive literature reviews in the ASCO and EORTC guidelines while the NCCN guidelines are more current based on systematic annual updates. The clarity of presentation also favors the NCCN guidelines with recommendations generally presented as both text and algorithmic diagram. All three new or updated guidelines recommend prophylactic use of the myeloid growth factors in patients at greater than a 20% risk of febrile neutropenia and in those with important factors increasing individual risk of neutropenic complications.

Objectives: To determine the effect of colony-stimulating factor (CSF) on incidence of febrile neutropenia, infection, and survival in older people with non-Hodgkin's lymphoma (NHL) treated with chemotherapy., Design: Retrospective cohort study., Setting: The Surveillance, Epidemiology, and End Results-Medicare database., Participants: Thirteen thousand two hundred twenty-three people diagnosed with NHL at age 65 and older (mean age 74.9, range 65-102) in 1992 to 2002 who received chemotherapy within 12 months of diagnosis., Measurements: Primary prophylaxis was defined as CSF administered at the start of chemotherapy before febrile neutropenia or infection; secondary prophylaxis was defined as CSF use after febrile neutropenia or infection., Results: Participants with five to nine administrations of primary prophylactic CSF had a 42% lower risk of febrile neutropenia (odds ratio (OR)=0.58, 95% confidence interval (CI)=0.41-0.83), and participants with 10 or more administrations had a 48% lower risk (OR=0.52, 95% CI=0.36-0.76) after adjusting for age, stage, histology, and comorbidity. Results did not differ significantly after adjusting for propensity score of receiving CSF. There was no significant association between primary prophylactic CSF and overall survival, but secondary prophylactic CSF was significantly associated with better survival. Four to 10 administrations of secondary prophylactic CSF was associated with 9% lower mortality risk (hazard ratio (HR)=0.91, 95% CI=0.84-0.99), 11 to 23 administrations was associated with 23% lower mortality risk (HR=0.77, 95% CI=0.71-0.84) and 24 or more administrations was associated with 13% lower mortality risk (HR=0.87, 95% CI+0.79-0.95) than in participants not receiving CSF after neutropenia or infection., Conclusion: Primary prophylactic CSF was observed to be effective in reducing the incidence of neutropenia and infection. These findings substantiate the clinical guidelines for recommending prophylactic CSF in older people with NHL receiving chemotherapy., (© 2010, Copyright the Authors. Journal compilation © 2010, The American Geriatrics Society.)

Background: In newly diagnosed patients with Hodgkin lymphoma (HL) the effect of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD)-related neutropenia on chemotherapy delivery is poorly documented. The aim of this analysis was to assess the impact of chemotherapy-induced neutropenia (CIN) on ABVD chemotherapy delivery in HL patients., Study Design: Data from two similarly designed, prospective, observational studies conducted in the US and the EU were analysed. One hundred and fifteen HL patients who started a new course of ABVD during 2002-2005 were included. The primary objective was to document the effect of neutropenic complications on delivery of ABVD chemotherapy in HL patients. Secondary objectives were to investigate the incidence of CIN and febrile neutropenia (FN) and to compare US and EU practice with ABVD therapy in HL. Pooled data were analysed to explore univariate associations with neutropenic events., Results: Chemotherapy delivery was suboptimal (with a relative dose intensity < or = 85%) in 18-22% of patients. The incidence of grade 4 CIN in cycles 1-4 was lower in US patients (US 24% vs. EU 32%). Patients in both the US and the EU experienced similar rates of FN across cycles 1-4 (US 12% vs. EU 11%). Use of primary colony-stimulating factor (CSF) prophylaxis and of any CSF was more common in the US than the EU (37% vs. 4% and 78% vs. 38%, respectively). The relative risk (RR) of dose delays was 1.54 (95% confidence interval [CI] 1.08-2.23, p = 0.036) for patients with vs. without grade 4 CIN and the RR of grade 4 CIN was 0.35 (95% CI 0.12-1.06, p = 0.046) for patients with vs. without primary CSF prophylaxis., Conclusions: In this population of HL patients, CIN was frequent and FN occurrence clinically relevant. Chemotherapy delivery was suboptimal. CSF prophylaxis appeared to reduce CIN rates.

Granulocyte transfusion can be used as supportive therapy in patients with life-threatening neutropenia caused by bone marrow failure or in patients with neutrophil dysfunction. Emerging evidence demonstrates the benefits of granulocyte transfusions to treat infections in patients after treatment with high-dose chemotherapy, particularly the chemotherapy associated with conditioning for hematopoietic stem cell transplant. There has been an increased interest in the use of therapeutic granulocyte transfusion in recent years due to the ability to use granulocyte colony-stimulated factors to produce higher doses of granulocytes for transfusion. Other factors that influence the outcome of transfusion include the type of infection being treated, the likelihood of recipient marrow recovery, and recipient alloimmunization. This article provides a historical perspective on granulocyte transfusion and an overview of its clinical use.

Aggressive treatment of childhood cancers including systemic antineoplastic and radiation therapy has secondary effects on a variety of normal cells including hematopoietic elements of the bone marrow, often causing neutropenia. Neutropenia increases the risk for serious infection and is associated with significant morbidity and mortality. The approach to the treatment of the febrile neutropenic pediatric patient has evolved considerably because high- and low-risk criteria have been defined and broad-spectrum antibiotics developed. This article reviews the concepts involved in the evaluation and management of febrile, neutropenic, pediatric cancer patients.

Neutropenia is a common complication of cancer chemotherapy. Colony-stimulating factors (CSF) may be used to avoid neutropenia-associated complications. The Spanish Society of Medical Oncology (SEOM) recently constituted a working group to review the main issues concerning the use of CSF and carried out a consensus process about the use of CSF in cancer patients, held in Madrid on 26 May 2006. The group concluded the following recommendations: prophylactic use of CSF is recommended when a rate of febrile neutropenia (FN) higher than 20% is expected without the use of CSF or when additional risk factors for neutropenia exist; therapeutic use of CSF is recommended in order to treat FN episodes but not to treat afebrile neutropenic episodes. In addition, the use of CSF is considered effective when used to mobilise stem cells before high-dose chemotherapy and when used for chemotherapy schedule optimisation in dose-dense and in dose-intense regimens.

Goals: Management of the risk of potential chemotherapy-induced neutropenic complications such as febrile neutropenia (FN) and severe neutropenia (SN) is a quality of care priority. How frequently does care at our institution conform to established guidelines?, Materials and Methods: This retrospective chart review study included a random sample of 305 cancer patients receiving care at a single US academic medical center. Abstracted data included demographics, risk factors, and outcome variables (e.g., development of FN/SN, administration of myeloid growth factors). To evaluate quality of care, we assessed conformance between actual practice and established clinical practice guidelines for the use of myeloid growth factors from the National Comprehensive Cancer Network (NCCN)., Main Results: Of the 305 cases reviewed, 8% were classified as low risk (<10%), 48% as intermediate risk (10-20%), and 44% as high risk (>20%), using the risk classifications in the NCCN guidelines modified to accommodate illness and other risk factors. Thirty-four percent received prophylactic administration of myeloid growth factors. Half of the cases had adequate documentation of mid-cycle absolute neutrophil count to determine whether FN/SN developed. Among these cases with adequate documentation, 21% developed FN/SN. Use of growth factors did not conform to established quality guidelines. Overall, 77 of 133 (58%) high-risk cases received myeloid growth factors, whereas six of 25 (24%) low-risk cases received myeloid growth factors., Conclusions: Routine clinical practice in this academic oncology setting was poorly aligned with established guidelines; there is substantial opportunity to standardize clinical strategies and increase conformance with evidence-based guidelines.

Myelosuppression, particularly febrile neutropenia (FN), are serious dose-limiting toxicities that occur frequently during the first cycle of chemotherapy. Identifying patients most at risk of developing FN might help physicians to target prophylactic treatment with colony-stimulating factor (CSF), in order to decrease the incidence, or duration, of myelosuppression and facilitate delivery of chemotherapy as planned. We present a risk model for FN occurrence in the first cycle of chemotherapy, based on a subgroup of 240 patients with non-Hodgkin lymphoma (NHL) enroled in our European prospective observational study. Eligible patients had an International Prognostic Index of 0-3, and were scheduled to receive a new myelosuppressive chemotherapy regimen with at least four cycles. Clinically relevant factors significantly associated with cycle 1 FN were older age, increasing planned cyclophosphamide dose, a history of previous chemotherapy, a history of recent infection, and low baseline albumin (<35 g/l). Prophylactic CSF use and higher weight were associated with a significant protective effect. The model had high sensitivity (81%) and specificity (80%). Our model, together with treatment guidelines, may rationalise the clinical decision of whether to support patients with CSF primary prophylaxis based on their risk factor profile. Further validation is required.

Objectives: Neutropenia and its complications, including febrile neutropenia (FN), are a common side effect of cancer chemotherapy. Results of clinical trials showed that prophylactic use of granulocyte colony-stimulating factors (G-CSF) is effective in preventing FN. In this study, the cost effectiveness (measured as cost per quality-adjusted time [days]) of three treatment alternatives were evaluated: no G-CSF, filgrastim administered daily for 7-12 days after chemotherapy, and a pegylated form of G-CSF pegfilgrastim, administered once per cycle., Methods: A cost-utility model based on standard clinical practice of treating FN with immediate hospitalization or with ambulatory treatment, from a societal perspective was developed. Direct medical cost estimates for hospitalization were derived from claims data reported by 115 US academic medical centers. Indirect medical costs, productivity costs, probabilities, and utilities are based on published literature. Results were subjected to sensitivity analyses and 95% confidence intervals are based on a Monte Carlo simulation., Results: Mean estimated costs/day of hospitalization were $1984 (SD $1040, N = 24,687) for surviving patients and $3139 (SD $2014, N = 1437) for dying patients. Under baseline conditions, pegfilgrastim dominated both filgrastim and no G-CSF, with expected costs and effectiveness of $4203 and 12.361 quality adjusted life-days (QALDs) for no G-CSF, $3058 and 12.967 QALDs for pegfilgrastim, and $5264 and 12.698 QALDs for filgrastim., Conclusions: This cost-utility analysis provides strong evidence that pegfilgrastim is not only cost-effective but also cost-saving in most common clinical and economic settings. There appear to be both clinical and economic benefits from prophylactic administration of pegfilgrastim.

Chemotherapy-induced neutropenia (CIN) is a common and serious toxicity of cancer chemotherapy. It can lead to febrile neutropenia (FN), which often requires patients to be hospitalised for intravenous antibiotic therapy. Chemotherapy dose reductions or delays, which can compromise clinical outcomes, may also result from CIN and FN. Prophylactic use of colony-stimulating factors (CSFs) reduces the incidence, duration, and severity of FN, and there is evidence that it helps maintain scheduled chemotherapy dose delivery. In 2006, three organisations published new or updated guidelines for the use of CSFs in cancer treatment. Each recommends that FN risk be determined individually for each patient, taking into account patient- and disease-specific risk factors, the chemotherapy regimen, and treatment intent. Particular consideration should be given to patients who are > or =65 years old, receiving chemotherapy regimens associated with > or =20% risk of FN, receiving dose-dense chemotherapy, and receiving treatment that is adjuvant, potentially curative, or intended to prolong survival. Accordingly, oncology nurses can play an important role in assessing and identifying patients at risk for FN before every chemotherapy cycle. There is evidence that, regardless of practice type or size, implementing guidelines for CSF use within a multidisciplinary team improves patient outcomes.

Chemotherapy-induced neutropenia is a major dose-limiting toxicity of systemic cancer chemotherapy that can lead to fever and infection, requiring prompt analysis and in-patient treatment with broad-spectrum antibiotics. Complicated neutropenia may lead to reduction and/or delay of systemic anti-cancer treatment, which may compromise outcome. Haematopoietic growth factors have the ability to augment haematopoietic cell cycling and are used to facilitate more dose-intense treatments and to decrease treatment-related complications. This review focuses on randomised trials that investigated the use of colony-stimulating factors (CSF) to prevent treatment-related febrile complications in haematological malignancies in (younger) adult patients. In general, these studies demonstrated that CSF reduced the duration of severe neutropenia but not always its febrile complications; therefore inconsistent results regarding clinically relevant reduction of hospitalisation, duration of therapeutic antibiotics, infection-related or disease-related mortality and economic effects were reported. Current developments in treatment of haematological malignancies will pose new challenges as a shift in infectious pathogens can be expected.

(1) Neutropenia is a frequent complication of chemotherapy associated with life-threatening infections, hospitalisation, and chemotherapy dose reductions and delays.(2) Primary prophylaxis with granulocyte colony-stimulating factors has been shown to reduce the incidence and duration of neutropenia, febrile neutropenia, infections, hospitalisation and antibiotic use.(3) Recent randomised clinical trials of filgrastim, lenograstim and pegfilgrastim showed variable results across patient groups at different risks of febrile neutropenia.(4) Pegfilgrastim is at least as effective as filgrastim in the prophylaxis of chemotherapy-induced neutropenia and has improved pharmacokinetics requiring reduced administration.

Purpose of Review: Neutropenic complications including febrile neutropenia represent major dose-limiting toxicities of cancer chemotherapy. Recommendations for the use of recombinant myeloid growth factors to reduce the risk of neutropenic complications and sustain dose intensity continue to evolve., Recent Findings: Several randomized controlled trials and meta-analyses have confirmed that the myeloid growth factors reduce the risk of neutropenic complications and may facilitate delivered dose intensity in patients receiving cancer chemotherapy. Older age and certain comorbidities significantly increase the risk of febrile neutropenia and its consequences. Three new clinical practice guidelines for the use of the myeloid growth factors have been published by major professional oncology organizations including the American Society of Clinical Oncology, the European Organization for Research and Treatment of Cancer and the National Comprehensive Cancer Network. The recommendations and evidence basis for these guidelines are presented here. All three new or updated guidelines recommend prophylactic use of the myeloid growth factors in cancer patients receiving chemotherapy at 20% or greater risk of febrile neutropenia and in those with important variables that increase individual risk of neutropenic complications., Summary: Consistent clinical practice guidelines based on multiple randomized control trials and meta-analyses should further guide the appropriate and cost-effective use of these agents.

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.

Febrile neutropenia is a relatively frequent event in cancer patients treated with chemotherapy. A relevant body of scientific evidence has been produced in the last 2 decades, through clinical trials addressing the efficacy of colony stimulating factors (CSFs) in the prevention and treatment of febrile neutropenia. The correct use of CSFs needs to be optimized, and several guidelines have been produced and periodically updated, in order to uniform and guide clinical practice. The aim of this review is to synthesize the most relevant clinical trials and the most important existing guidelines about the role of CSFs in solid tumours. Role of CSFs as primary prophylaxis, secondary prophylaxis and treatment of afebrile and febrile neutropenia is discussed. A special focus is dedicated to neutropenia and the use of CSFs in the treatment of the three "big killers" among the solid tumours: breast cancer, lung cancer and colorectal cancer.

Purpose/objectives: To review and determine the applicability of the 2006 National Comprehensive Cancer Network (NCCN) clinical practice guidelines for the use of myeloid growth factors in adult patients treated with chemotherapy for solid tumors and nonmyeloid malignancies., Data Sources: Published guidelines, original research, review articles, and conference presentations., Data Synthesis: Chemotherapy-induced neutropenia is a common adverse effect of myelosuppressive chemotherapy that may lead to life-threatening infections, prolonged hospitalization, increased IV antibiotic use, and dose reductions or delays that affect patients' quality of life and clinical outcomes., Conclusions: Before treatment begins, nurses should determine which patients are at greater risk for chemotherapy-induced neutropenia and implement an appropriate plan of care., Implications for Nursing: Nurses are in an ideal position to implement a risk assessment tool and play an integral role in directing the quality of patient care. Implementing the NCCN guidelines is one way to facilitate standardization of care.

Three different practice guidelines for the myeloid growth factors were recently published by major professional organizations. A comprehensive review and comparison of the guidelines using a priori structured content criteria and a previously validated quality appraisal tool are reported. The final recommendations from these guidelines are consistent for primary prophylaxis with the colony-stimulating factors (CSFs) when the risk of febrile neutropenia is in the range of 20% or greater. All 3 guidelines also recommend prophylactic use of myeloid growth factors in patients with important factors increasing individual risk of neutropenic complications. The recommendation that patients receiving regimens associated with lower risk should have CSF use guided by individual risk assessment is also consistent. Critical quality appraisal indicates that the scope, purpose, stakeholder involvement, and applicability of these guidelines differ little. The American Society of Clinical Oncology and European Organization for Research and Treatment of Cancer guidelines place more emphasis on comprehensive literature reviews, and the National Comprehensive Cancer Network guidelines are more current based on systematic annual updates. Presentation clarity also favors National Comprehensive Cancer Network guidelines, with recommendations generally presented as both text and algorithmic diagram.

The chemotherapy of most cancers may be beneficial to older individuals as long as patients are selected on the basis of their life expectancy and functional reserve, conditions that may interfere with the tolerance of chemotherapy are corrected, and adequate doses of chemotherapy are administered. Prevention of neutropenia-related infection may both improve the outcome of cancer and reduce the risk of toxic deaths in older patients. The prophylactic use of myelopoietic growth factors is recommended in individuals aged 65 and older when the risk of chemotherapy-induced neutropenic infection is at least 10% or higher. In this article we explore the management of neutropenia and neutropenic infections in older cancer patients, as well as review the causes and the risk of this complication.

Grade 3 and 4 neutropenia as well as febrile neutropenia have been demonstrated to occur in all tumor types and are clearly associated with major morbidity and significant mortality; this is particularly true when myelosuppressive regimens are used with curative intent as is the case in most breast cancer and non-Hodgkin's lymphoma regimens. Myeloid colony-stimulating factors (CSFs) substantially decrease the risk of severe and febrile neutropenia. Although the white cell growth factors might not be cost-effective at lower risks of febrile neutropenia, they clearly benefit other outcomes such as the incidence of severe neutropenia and febrile neutropenia, hospitalization, and mortality. Updated guidelines from the American Society of Clinical Oncology, the National Comprehensive Cancer Network, and the European Organisation for Research and Treatment of Cancer now recommend primary prophylaxis or first-cycle use of white cell growth factors with regimens where the occurrence of febrile neutropenia is approximately 20% (as well as when other risk factors are present). This article briefly describes the rationale for the development of several of the guideline changes as well as highlights some of the ongoing issues related to the use of CSFs.

Purpose: To update the 2000 American Society of Clinical Oncology guideline on the use of hematopoietic colony-stimulating factors (CSF)., Update Methodology: The Update Committee completed a review and analysis of pertinent data published from 1999 through September 2005. Guided by the 1996 ASCO clinical outcomes criteria, the Update Committee formulated recommendations based on improvements in survival, quality of life, toxicity reduction and cost-effectiveness., Recommendations: The 2005 Update Committee agreed unanimously that reduction in febrile neutropenia (FN) is an important clinical outcome that justifies the use of CSFs, regardless of impact on other factors, when the risk of FN is approximately 20% and no other equally effective regimen that does not require CSFs is available. Primary prophylaxis is recommended for the prevention of FN in patients who are at high risk based on age, medical history, disease characteristics, and myelotoxicity of the chemotherapy regimen. CSF use allows a modest to moderate increase in dose-density and/or dose-intensity of chemotherapy regimens. Dose-dense regimens should only be used within an appropriately designed clinical trial or if supported by convincing efficacy data. Prophylactic CSF for patients with diffuse aggressive lymphoma aged 65 years and older treated with curative chemotherapy (CHOP or more aggressive regimens) should be given to reduce the incidence of FN and infections. Current recommendations for the management of patients exposed to lethal doses of total body radiotherapy, but not doses high enough to lead to certain death due to injury to other organs, includes the prompt administration of CSF or pegylated G-CSF.

Background: The colony-stimulating factors (CSFs) are widely utilized to prevent neutropenic complications in both adults and children, but randomized controlled trials in the pediatric setting have reported varied results. A systematic review of the literature and meta-analysis were conducted to definitively assess the impact of prophylactic CSFs on the risk of febrile neutropenia (FN) in pediatric oncology patients., Methods: MEDLINE was searched and references hand-searched through July 2004 for randomized controlled trials of prophylactic G-CSF or GM-CSF in pediatric oncology patients. Objectives, outcomes, and quality of the 16 included studies were extracted by two reviewers. Weighted summary estimates of relative risks (RR) were calculated for FN and documented infection (DI). Mean differences in hospitalization, antibiotic use, and duration of neutropenia were calculated., Results: FN occurred in 68% of 400 controls and 59% of 404 CSF patients. The estimated RR was 0.88 [0.81-0.97; (P=0.01)] favoring the CSFs for leukemia and high grade lymphoma studies and 0.71 [0.51-0.97; (P=0.03)] for solid tumor studies. DI occurred in 25% of controls and 20% of CSF patients for an estimated RR of 0.80 [0.61-1.06; (P=0.12)]. The mean decrease in duration of neutropenia was 3.5 days [2.2-4.7; (P<0.0001)]. Mean decreases favoring CSF use were also observed for hospital stay of 1.7 days [0.9-2.5 (P<0.01)] and antibiotic use of 2.0 days [0.4-3.6; P=0.02]., Conclusions: Prophylactic CSFs significantly decrease the incidence of FN and the durations of severe neutropenia, hospitalization, and antibiotic use in pediatric cancer patients, but they do not significantly decrease documented infections.

Neutropenia represents a major dose-limiting toxicity of chemotherapy and is associated with an increased risk of infection, impaired patient quality of life, and interference with the delivery of full-dose chemotherapy. These complications increase not only morbidity and mortality associated with cancer treatment but also the overall cost of care for cancer patients. Conversely, chemotherapy-induced neutropenia as a surrogate for delivered dose intensity has been associated with improved cancer survival. Administration of myeloid growth factors, such as filgrastim and pegfilgrastim, reduces the risk for neutropenic complications and facilitates the delivery of full-dose chemotherapy. There is an ongoing effort to identify patients at increased risk for developing neutropenic complications who would likely benefit from preemptive myeloid growth factor therapy. Appropriate use of myeloid growth factors is associated with reduced neutropenic complications, improved patient quality of life, and potentially improved disease control and long-term survival.

Currently, 2 granulocyte colony-stimulating factors are available in the United States--filgrastim and pegfilgrastim. In patients receiving chemotherapy for solid tumors, lymphoma, and acute myelogenous leukemia, these agents reduce the duration of severe neutropenia, decrease the incidence of febrile neutropenia, and facilitate on-time delivery of scheduled doses of chemotherapy. In addition, substantial data document the benefits of using these agents in patients undergoing peripheral blood progenitor cell mobilization and in patients who have undergone bone marrow transplantation or peripheral blood progenitor cell transplantation. Recent studies suggest that for all of these indications, the efficacy of pegfilgrastim, the newest agent, is comparable to or greater than that of filgrastim. Like filgrastim, pegfilgrastim is generally well tolerated. An important advantage of pegfilgrastim, however, is its once-per-cycle schedule of administration. Patients and health care providers are likely to prefer the administration schedule of pegfilgrastim to the daily administration schedule required with the use of filgrastim. Furthermore, the more convenient schedule of pegfilgrastim may be associated with greater treatment adherence and increased patient quality of life.

Objective: Recombinant granulocyte colony-stimulating factors (G-CSF) have been shown to be effective in reducing the risk of infections associated with antitumour chemotherapy. This report describes a single-centre experience of the efficacy of pegfilgrastim compared with filgrastim or lenograstim in reducing the incidence of febrile neutropenia in patients receiving combination chemotherapy with taxane and epirubicin in a neoadjuvant and adjuvant setting., Methods: A total of 118 patients with breast cancer were treated with either epirubicin 75 mg/m(2) and docetaxel 75 mg/m(2) or epirubicin 90 mg/m(2) and paclitaxel 200 mg/m(2) every 3 weeks; 88 received G-CSF support with daily filgrastim or lenograstim and 30 with pegfilgrastim once per cycle., Results: Eight patients (9.1%) with prophylactic filgrastim or lenograstim support developed febrile neutropenia, as well as 1 patient (3.3%) in the pegfilgrastim group (p = 0.445). Febrile neutropenia occurred in 13 (2.7%) of 476 filgrastim or lenograstim supported chemotherapy cycles and in 2 (1.2%) of 172 cycles with pegfilgrastim support (p = 0.376). The frequency of chemotherapy delays and dose reductions was not significantly different between the two G-CSF treatment groups., Conclusion: These data show a trend towards superiority of pegfilgrastim over filgrastim or lenograstim in reducing the frequency of febrile neutropenia in patients treated with taxane and epirubicin chemotherapy regimens for breast cancer., (Copyright (c) 2006 S. Karger AG, Basel.)

Febrile neutropenia is a serious side effect of chemotherapy. Colony-stimulating factors (CSFs) are used for primary and secondary treatment in patients with grade 4 neutropenia. The use of CSFs is expensive and accompanied by side effects. In the current study, Life-Mel Honey (LMH) was administered to prevent neutropenia and to reduce the need for CSFs in patients treated with chemotherapy. Thirty cancer patients receiving chemotherapy for primary or metastatic disease were included. All patients had grade 4 neutropenia and were treated with CSFs. The patients repeated the same chemotherapy schedule, with the addition of LMH for 5 d. Blood count was performed weekly. There was no recurrence of neutropenia after LMH intake and no need for treatment with CSFs in 12 (40%) of patients. Eighteen (60%) patients with LMH developed neutropenia grade 4 and were treated with CSFs (p=0.007). Hemoglobin levels remained >11 g/dL during LMH intake in 19 (64%) patients. Only three (10%) patients had thrombocytopenia. Eight (32%) patients reported improvement in quality of life. The use of LMH in patients who are at high risk of developing neutropenia as a result of chemotherapy decreases the risk of pancytopenia and the need for CSFs. LMH is inexpensive, has no side effects, and is easy to administer.

High risk febrile neutropenia requires hospital treatment. The choice of antibiotic is determined by the resistance patterns of the pathogens predominating in each center. Monotherapy with an antipseudomonal beta-lactam can be the initial choice in most patients. However, initial beta-lactam-aminoglycoside combination therapy should be considered with infectious foci other than the catheter, in non-fermenting Gram-negative colonization, and when the patient has received beta-lactam treatment in the previous month. Combination therapy with glycopeptides should be considered if the focus of infection is the catheter, if there is colonization by methicillin-resistant Staphylococcus aureus or severe mucositis and both agents should be administered if there are criteria for severe sepsis. If there is no microbiologically documented infection, glycopeptides and/or aminoglycosides should be withdrawn promptly. Empirical antifungal therapy plays an important role in patients with persistent fever. In severe microbiologically documented infections, therapy should be maintained for a minimum of 14 days. Adjuvant therapy with granulopoiesis-stimulating factors is indicated in most patients.

Neutropenia is a frequent dose-limiting complication of chemotherapy. Although myeloid growth factors decrease the risk of febrile neutropenia and the resulting complications of hospitalizations, dose delays, and dose reductions, not all patients need or benefit from the prophylactic administration of myeloid growth factors. A recent risk model showed that the predictors of febrile neutropenia include anthracycline use, poor performance status, and low pretreatment blood counts. These predictors may be used in addition to the intensity of the chosen chemotherapy regimen to determine whether a patient warrants primary prophylaxis with myeloid growth factors. The 2005 guidelines of the National Comprehensive Cancer Network call for primary prophylactic use in all patients with a risk of febrile neutropenia above 20%. Other recent studies show that pegylated filgrastim is also effective at preventing febrile neutropenia in patients receiving intermediate- risk chemotherapy.

Granulocyte colony-stimulating factor (CSF) and granulocyte-macrophage CSF are potent drugs used to increase neutrophil counts after myelosuppressive chemotherapy. However, in various indications, the use of CSFs has no clinical benefit with regard to morbidity or mortality from infectious complications, frequency of antibiotic use, or rate of hospitalization. Thus, the application of CSFs should be limited to indications with proven clinical benefits or evidence of cost-effectiveness. This review will provide an overview of the state-of-the-art use of CSFs in chemotherapy-associated neutropenia, transplantation, and bone marrow failure syndromes. In addition, recently developed drugs for accelerated hematopoietic recovery will be presented.

The prophylactic use of myeloid growth factors reduces the risk of chemotherapy-induced neutropenia and its complications, including febrile neutropenia and infection-related mortality. Perhaps most importantly, the prophylactic use of colony-stimulating factors (CSFs) has been shown to reduce the need for chemotherapy dose reductions and delays that may limit chemotherapy dose intensity, thereby increasing the potential for prolonged disease-free and overall survival in the curative setting. National surveys have shown that the majority of patients with potentially curable breast cancer or non-Hodgkin's lymphoma (NHL) do not receive prophylactic CSF support. In this issue, the National Comprehensive Cancer Network presents guidelines for the use of myeloid growth factors in patients with cancer. These guidelines recommend a balanced clinical evaluation of the potential benefits and harms associated with chemotherapy to define the treatment intention, followed by a careful assessment of the individual patient's risk for febrile neutropenia and its complications. The decision to use prophylactic CSFs is then based on the patient's risk and potential benefit from such treatment. The routine prophylactic use of CSFs in patients receiving systemic chemotherapy is recommended in patients at high risk (>20%) of developing febrile neutropenia or related complications that may compromise treatment. Where compelling clinical indications are absent, the potential for CSF prophylaxis to reduce or offset costs by preventing hospitalization for FN should be considered. The clinical, economic, and quality of life data in support of these recommendations are reviewed, and important areas of ongoing research are highlighted.

Purpose: Current treatment for febrile neutropenia (FN) includes hospitalization for evaluation, empiric broad-spectrum antibiotics, and other supportive care. Clinical trials have reported conflicting results when studying whether the colony-stimulating factors (CSFs) improve outcomes in patients with FN. This Cochrane Collaboration review was undertaken to further evaluate the safety and efficacy of the CSFs in patients with FN., Methods: An exhaustive literature search was undertaken including major electronic databases (CANCERLIT, EMBASE, LILACS, MEDLINE, SCI, and the Cochrane Controlled Trials Register). All randomized controlled trials that compare CSFs plus antibiotics versus antibiotics alone for the treatment of established FN in adults and children were sought. A meta-analysis of the selected studies was performed., Results: More than 8,000 references were screened, with 13 studies meeting eligibility criteria for inclusion. The overall mortality was not influenced significantly by the use of CSF (odds ratio [OR] = 0.68; 95% CI, 0.43 to 1.08; P = .1). A marginally significant result was obtained for the use of CSF in reducing infection-related mortality (OR = 0.51; 95% CI, 0.26 to 1.00; P = .05). Patients treated with CSFs had a shorter length of hospitalization (hazard ratio [HR] = 0.63; 95% CI, 0.49 to 0.82; P = .0006) and a shorter time to neutrophil recovery (HR = 0.32; 95% CI, 0.23 to 0.46; P < .00001)., Conclusion: The use of the CSFs in patients with established FN caused by cancer chemotherapy reduces the amount of time spent in hospital and the neutrophil recovery period. The possible influence of the CSFs on infection-related mortality requires further investigation.