Search

Importance: Colony-stimulating factors are prescribed to patients undergoing chemotherapy to reduce the risk of febrile neutropenia. Research suggests that 55% to 95% of colony-stimulating factor prescribing is inconsistent with national guidelines., Objective: To examine whether a guideline-based standing order for primary prophylactic colony-stimulating factors improves use and reduces the incidence of febrile neutropenia., Design, Setting, and Participants: This cluster randomized clinical trial, the Trial Assessing CSF Prescribing Effectiveness and Risk (TrACER), involved 32 community oncology clinics in the US. Participants were adult patients with breast, colorectal, or non-small cell lung cancer initiating cancer therapy and enrolled between January 2016 and April 2020. Data analysis was performed from July to October 2021., Interventions: Sites were randomized 3:1 to implementation of a guideline-based primary prophylactic colony-stimulating factor standing order system or usual care. Automated orders were added for high-risk regimens, and an alert not to prescribe was included for low-risk regimens. Risk was based on National Comprehensive Cancer Network guidelines., Main Outcomes and Measures: The primary outcome was to find an increase in colony-stimulating factor use among high-risk patients from 40% to 75%, a reduction in use among low-risk patients from 17% to 7%, and a 50% reduction in febrile neutropenia rates in the intervention group. Mixed model logistic regression adjusted for correlation of outcomes within a clinic., Results: A total of 2946 patients (median [IQR] age, 59.0 [50.0-67.0] years; 2233 women [77.0%]; 2292 White [79.1%]) were enrolled; 2287 were randomized to the intervention, and 659 were randomized to usual care. Colony-stimulating factor use for patients receiving high-risk regimens was high and not significantly different between groups (847 of 950 patients [89.2%] in the intervention group vs 296 of 309 patients [95.8%] in the usual care group). Among high-risk patients, febrile neutropenia rates for the intervention (58 of 947 patients [6.1%]) and usual care (13 of 308 patients [4.2%]) groups were not significantly different. The febrile neutropenia rate for patients receiving high-risk regimens not receiving colony-stimulating factors was 14.9% (17 of 114 patients). Among the 585 patients receiving low-risk regimens, colony-stimulating factor use was low and did not differ between groups (29 of 457 patients [6.3%] in the intervention group vs 7 of 128 patients [5.5%] in the usual care group). Febrile neutropenia rates did not differ between usual care (1 of 127 patients [0.8%]) and the intervention (7 of 452 patients [1.5%]) groups., Conclusions and Relevance: In this cluster randomized clinical trial, implementation of a guideline-informed standing order did not affect colony-stimulating factor use or febrile neutropenia rates in high-risk and low-risk patients. Overall, use was generally appropriate for the level of risk. Standing order interventions do not appear to be necessary or effective in the setting of prophylactic colony-stimulating factor prescribing., Trial Registration: ClinicalTrials.gov Identifier: NCT02728596.

Background: Guidelines recommend primary prophylactic use of colony-stimulating factor (PP-CSF) when risk of febrile neutropenia (FN) - based on chemotherapy and patient risk factors - is high. Whether and how PP-CSF use may have changed over time (e.g. due to guideline revisions, increasing use of myelosuppressive regimens, controversy regarding inappropriate CSF use), and whether there has been a concomitant change in the incidence of FN, is unknown., Methods: A retrospective cohort design and data from two US healthcare claims repositories were employed. The study population included patients who had non-metastatic cancer of the breast, colon/rectum, lung or ovaries, or non-Hodgkin's lymphoma (NHL), and who received myelosuppressive chemotherapy regimens with an intermediate/high risk for FN. For each patient, the first cycle of the first course was characterized in terms of PP-CSF use and FN episodes. Crude incidence proportions for PP-CSF and FN during the first cycle were estimated by calendar quarter (2010-2016); multivariable logistic regression models were used to estimate quarter-specific adjusted mean probabilities of FN by PP-CSF use., Results: The study population totaled 142,730 patients with breast cancer (61%), colorectal cancer (14%), NHL (11%), ovarian cancer (10%) or lung cancer (5%). PP-CSF use increased from 52% in 1Q2010 to 58% in 4Q2016; pegfilgrastim was the most commonly used agent (>96% across quarters). PP-CSF administration on the same day as chemotherapy ranged from 8 to 11% until 1Q2015, and increased to 64% by 4Q2016. Adjusted incidence proportions for FN in the first chemotherapy cycle ranged from 2.7% (95% CI: 2.3-3.0) to 3.7% (95% CI: 3.1-4.3) among those who did not receive PP-CSF, and was 2.6% (95% CI: 2.5-2.7) across quarters among those who received PP-CSF., Conclusions: Although the use of PP-CSF is commonplace in current US clinical practice, underutilization in cancer patients receiving chemotherapy regimens with an intermediate/high risk for FN may still be an issue. Use of same-day PP-CSF increased markedly from the end of 2015, although this finding reflects (at least in part) increased uptake of pegfilgrastim delivered via an on-body injector as well as the recent change in clinical practice guidelines. Overall, patients receiving PP-CSF appear to have a lower risk of FN during the first cycle of chemotherapy.

Colony stimulating factors (CSF) are widely prescribed to avoid febrile neutropenia (FN) among cancer patients receiving chemotherapy, but studies show their use is often not consistent with practice guidelines. In addition, there is limited high quality evidence assessing benefits and harms of primary prophylactic-CSF (PP-CSF) in the setting of chemotherapy that poses an intermediate risk of FN. To address these issues, with funding from the Patient Centered Outcomes Research Institute (PCORI) and the National Cancer Institute's Community Oncology Research Program, SWOG is sponsoring a prospective, cluster randomized controlled pragmatic trial of an automated order entry protocol for PP-CSF among patients with breast, lung and colorectal cancer receiving myelosuppressive chemotherapy, with a nested randomized controlled trial of PP-CSF for patients receiving intermediate risk chemotherapy. Primary outcomes include adherence to practice guidelines, overall rates of FN and rates of FN among persons receiving intermediate risk chemotherapy. The study, the first pragmatic trial in the National Cancer Institute's cancer cooperative clinical trials network, will provide critical evidence to inform physician and patient decision-making around PP-CSF use and practice policies regarding automated orders in cancer components.

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.

Appropriate use of myeloid growth factors may reduce the risk of neutropenic complications including febrile neutropenia (FN) in patients receiving cancer chemotherapy. The recently updated American Society of Clinical Oncology (ASCO) Guidelines on the Use of the White Blood Cell Growth Factors recommends routine prophylaxis with these agents starting in the first cycle when the risk of FN is 20% or greater. However, the risks for neutropenic complications and the risk of serious adverse consequences from FN vary considerably with different chemotherapy regimens as well as other disease-, treatment-, and patient-specific risk factors. Considerably more information is now available on the major risk factors for FN. Multivariable risk models combining factors look promising but require further validation. Most clinical studies of myeloid growth factor prophylaxis assessed relative risk (RR) of FN but were not powered to evaluate the effect of prophylaxis on disease-free or overall survival. Accumulating evidence suggests, however, that the appropriate use of these agents in selected patients may improve both short-term and long-term survival by reducing the immediate risk of mortality accompanying patients with high-risk disease developing FN as well as improving disease-free and overall survival by enabling the delivery of full dose intensity chemotherapy and reducing the risk of disease recurrence in patients treated with curative intent. Further studies to evaluate risk factors and models for FN are needed to guide clinical and shared decision making for the optimal personalized use of these agents and offer patients at increased risk the best chance of long-term disease control.

Purpose: The American Society of Clinical Oncology (ASCO)/American Board of Internal Medicine (ABIM) Choosing Wisely (CW) measures aim to reduce the use of interventions that lack evidence of benefit in cancer care. The study presented here characterized adherence to the 2012 ASCO/ABIM CW recommendations by linking health plan claims data with a regional cancer registry and sought to identify areas for research interventions to improve adherence., Methods: SEER records for patients diagnosed with cancer in Western Washington State between 2007 and 2014 were linked with enrollment and claims from a large regional commercial insurance plan. Using claims and SEER records, algorithms were developed to characterize adherence to each CW measure. In addition, we calculated differences in total reimbursements and procedure-specific reimbursements for patients receiving adherent and nonadherent care., Results: A total of 22,359 unique individuals with cancer were linked with insurance enrollment records and met basic eligibility criteria. Overall adherence varied from 53% (breast surveillance) to 78% (breast staging). Within each measure, adherence varied substantially by stage at diagnosis and by cancer site in situations in which the CW measure affected multiple types of cancer. The difference in reimbursements between adherent and nonadherent populations across all five measures was approximately $29 million., Conclusion: Adherence to the ASCO/ABIM CW measures varies widely, as does the cost implication of nonadherence. A structured approach to evaluating adherence and cost impact is needed before developing programs aimed at improving adherence to the ASCO/ABIM CW measures., (Copyright © 2015 by American Society of Clinical Oncology.)

Aims: To examine the impact of research design on results in two published comparative effectiveness studies., Methods: Guidelines for comparative effectiveness research have recommended incorporating disease process in study design. Based on the recommendations, we develop a checklist of considerations and apply the checklist in review of two published studies on comparative effectiveness of colony-stimulating factors. Both studies used similar administrative claims data, but different methods, which resulted in directionally different estimates., Results: Major design differences between the two studies include: whether the timing of intervention in disease process was identified and whether study cohort and outcome assessment period were defined based on this temporal relationship., Conclusion: Disease process and timing of intervention should be incorporated into the design of comparative effectiveness studies.

The colony-stimulating factors (CSFs) are the master regulators of granulocyte and macrophage populations. There are four different aspects of the connection between the CSFs and cancer: (a) the CSFs can accelerate the regeneration of protective white cells damaged by chemotherapy; (b) the CSFs can mobilize stem cells to the peripheral blood in convenient numbers for transplantation; (c) the CSFs can enhance anticancer immune responses and (d) the CSFs are potentially involved in the genesis of the myeloid leukemias.

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.

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.)

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.

Purpose of Review: Clinical practice guidelines for the prevention of febrile neutropenia in patients receiving cancer chemotherapy utilizing the myeloid growth factors have been developed by several major international professional organizations. This review provides updates on the current status of these guidelines and summarizes recent reported studies currently under review by guideline panels which may alter guideline recommendations., Recent Findings: Whereas the consensus guidelines from the National Comprehensive Cancer Network (NCCN) are updated annually, previous evidence-based recommendations from the American Society of Clinical Oncology (ASCO) and the European Organisation for Research and Treatment of Cancer (EORTC) are currently undergoing an update in their evidence base and recommendations. These updates will consider and base new recommendations on recent important studies related to the efficacy, safety, and cost of these agents in the prevention of neutropenic complications including febrile neutropenia. New information relating to the risk of second malignancies and the ability of the myeloid growth factors to sustain or increase chemotherapy dose intensity and improve overall survival is reviewed., Summary: Current guideline recommendations for the prevention of febrile neutropenia are reviewed along with recent published results likely to alter future guideline recommendations on the use of these agents.

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.

Due to the movement of hematopoietic stem cells through the bone marrow environment, it may be possible to effectively harvest peripheral blood stem cells in a second apheresis within a few hours after a first apheresis. In a retrospective analysis, 107 aphereses were performed in consecutive 33 pediatric and six healthy pediatric donors who received granulocyte-colony stimulating factor at 10 microg/kg/day or 400 microg/m(2)/day for five days. The median age and weight of cases were seven yr (range 1-19) and 20 kg (range 8-87). The toxicities related to apheresis procedure were minimal in both aphereses. In 22 double aphereses, the average number of CD34-positive cells per body weight (kg) collected was 5.3 +/- 4.2 (range 0.6-16.6) and 4.7 +/- 3.1 (range 0.2-10.9) x 10(6) in the first and second aphereses, respectively (p = 0.569). Multivariate analysis showed that number of CD34-positive cells collected in the first apheresis (p = 0.008) was an independent factor of increased CD34-positive cells in the second apheresis. Double apheresis in a single day was feasible and this procedure may be able to lessen the burden of apheresis compared to two consecutive-day apheresis.

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.

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.

(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.

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.

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.

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.

The prevention of infection is an important outcome to measure in patients with cancer because infectious complications are a significant cause of morbidity and mortality. Nurses play a vital role in the prevention of infection in patients with cancer through nursing practice, research, and patient education. However, many common nursing interventions to prevent infection are based on tradition or expert opinion and have not been subjected to scientific examination. The 2005 Oncology Nursing Society Prevention of Infection Outcomes Intervention Project Team reviewed, critiqued, and summarized the research evidence for nursing interventions to prevent infections in patients with cancer. Pharmacologic and nonpharmacologic interventions were included because many advanced practice nurses prescribe medications. This article is an evidence-based review of nursing interventions to prevent infection in patients with cancer.

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.

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.

This session applied an interactive case study format to explore the healing properties of colony-stimulating factors (CSFs). Diarrhea, oral mucositis, wound healing, and Crohn disease are four specific areas in which CSFs have had success. The presenters also covered the signs and symptoms of conditions for which CSFs may be helpful.

Background: Neutropenia and its complications represent the major dose-limiting toxicity of cancer chemotherapy, especially in the elderly. Hematopoietic growth factors have been shown to reduce the severity and duration of febrile neutropenia (FN) and to sustain chemotherapy dose intensity., Methods: A systematic review was undertaken of studies of the relationship between age and the risk of neutropenia and its complications. Recent studies of the "Awareness of Neutropenia in Chemotherapy Study Group" related to the impact of age on neutropenic complications are also summarized., Results: The risk of FN associated with standard regimens increases with age and appears to be greatest during the first cycle of chemotherapy. FN continues to have a considerable clinical, economic, and quality-of-life impact on affected individuals. The risk of mortality associated with hospitalization with FN also increases with age but is largely associated with the higher rate of comorbidities observed in the elderly population. Despite increasing evidence that elderly patients experience similar benefit from cancer chemotherapy, reductions in dose intensity often compromise response rates and long-term survival. The hematopoietic growth factors reduce the risk of neutropenic events and the need for reduced dose intensity in elderly cancer patients. Primary prophylaxis with colony-stimulating factors (CSFs) reduces the risk of FN and its complications in elderly patients receiving moderately intensive systemic chemotherapy for responsive malignancies. CSFs also appear to reduce cost and improve quality of life in selected elderly patients receiving chemotherapy., Conclusions: Primary prophylaxis with CSFs should be considered in elderly patients with responsive and potentially curable malignancies who receive moderately intensive chemotherapy.

Hematological toxicity is the most common and the most frequent fatal complication of chemotherapy. It is observed with increased frequency with age, it is a significant independent predictor of the development of febrile neutropenia, and may contribute to a reluctance to administer chemotherapy in the elderly patient population. The authors analyze published data on effectiveness and results of the use of colony stimulating factors for preventing and treating elderly patients affected by tumors during chemotherapy.

Aging is associated with decreased functional reserve of multiple organ systems and with changes in the pharmacokinetics and pharmacodinamics of drugs. Older individuals express enhanced susceptibility to the complications of cytotoxic chemotherapy, especially to myleotoxicity, mucositis, cardiotoxicity and neurotoxicity. The management of older individuals with chemotherapy involves then prevention of these complications. General precautions include proper patient selection, based on the comprehensive geriatric assessment (CGA), dose adjustment for agents that are renally excreted to the patient creatinine clearance and maintenance of hemoglobin levels > or =12 g/dl. Filgrastim and pegfilgrastim proved effective in reducing by 50-75% the risk of neutropenic fever in older individuals treated with CHOP and CHOP-like chemotherapy and should be used for the prophilaxis of infections. When feasible, the oral agent capecitabine, should be used in lieu of intravenous fluorinated pyrimidines, to prevent mucositis. In patients at risk of cardiomyopathy from anthracyclines, dexrazoxane or liposomal compounds may be indicated. When toxicity is properly prevented, cytotoxic chemotherapy may be as effective in older individuals as it is in the younger ones.

Cytotoxic chemotherapy suppresses the hematopoietic system, impairing host protective mechanisms. One important consequence, chemotherapy-induced neutropenia (CIN), places patients at risk of developing fever and life-threatening infections. These complications have substantial economic impact and may severely affect the quality of life of patients undergoing treatment of cancer. Currently, CIN is managed by delaying and reducing chemotherapy treatment with hematopoietic growth factors and with intravenous antibiotic therapy. Reducing chemotherapy may compromise treatment outcomes in potentially curable malignancies, such as early stage breast cancer and non-Hodgkin's lymphoma. Randomized clinical trials have clearly shown that granulocyte colony-stimulating factor (filgrastim) and the longer-acting pegylated granulocyte colony-stimulating factor pegfilgrastim, when administered 24 hours after chemotherapy before the occurrence of CIN, are effective in reducing the incidence and severity of neutropenia and its complications, including administration of full doses of chemotherapy without treatment delay. Dose-dense chemotherapy, ie, the administration of standard-dose chemotherapy in shorter cycles (made feasible with growth factor support), has recently been shown to improve outcomes in early stage breast cancer and non-Hodgkin's lymphoma. This review summarizes the clinical consequences of CIN and describes current best practices for the management of patients at risk for CIN.

Neutropenia and its subsequent infectious complications represent the most common dose-limiting toxicity of cancer chemotherapy. Febrile neutropenia (FN) occurs with common chemotherapy regimens in 25 to 40% of treatment-naive patients, and its severity depends on the dose intensity of the chemotherapy regimen, the patient's prior history of either radiation therapy or use of cytotoxic treatment, and comorbidities. The occurrence of FN often causes subsequent chemotherapy delays or dose reductions. It may also lengthen hospital stay, increase monitoring, diagnostic and treatment costs, and reduce patient quality of life. A decade after their introduction, colony-stimulating factors (CSFs) such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are now an integral part of the prevention of potentially life-threatening FN; however, only G-CSF has US Food and Drug Administration approval for use in chemotherapy-induced neutropenia. These adjunctive agents accelerate formation of neutrophils from committed progenitors, thereby reducing the duration and severity of neutropenia. Important uses of CSFs in oncology are prevention of FN after chemotherapy, treatment of febrile neutropenic episodes and support following bone marrow transplantation, and collection of CSF-mobilised peripheral blood progenitor cells. G-CSF is used more frequently than GM-CSF for all of these indications because of fewer associated adverse effects. Clinical trials to date have not demonstrated a significant effect on overall survival or disease-free survival, which is most likely to be due to small sample size and lack of power to prove effect. However, they have demonstrated clinical utility in allowing the delivery of planned chemotherapy dose on schedule, an important clinical goal especially in curative tumour settings. The high cost of these agents limits their widespread use. Current American Society of Clinical Oncology guidelines recommend primary prophylaxis, or first cycle use, with CSFs being confined to patients with > or = 40% risk of FN, which may include elderly patients and other high-risk patients. In addition to the risk of FN, primary prophylaxis should also be considered if the patient has risk factors that place them in the Special Circumstances category. These risk factors may include decreased immune function in patients who are already at an increased risk of infection and pre-existing neutropenia due to disease, extensive prior chemotherapy, or previous irradiation to the pelvis or other areas containing large amounts of bone marrow. Future studies are needed to better define the patients most likely to benefit from CSF therapy, both for prophylaxis and as an adjunct to antibiotics for treatment of FN. Other potential uses include combination therapy with stem cell factors and other cytokines to boost progenitor cell development, maintaining dose intensity of salvage therapy in metastatic cancer patients, and application in patients with pneumonia, Crohn's fistulas, diabetic foot infections and a variety of other infectious conditions.

The hematopoietic colony-stimulating factors have been introduced into clinical practice as additional supportive measures that can reduce, but not eliminate infectious complications associated with therapy-induced neutropenia. Over the past decade, we have begun to appreciate the subtler aspects of the proper use of G-CSF and GM-CSF, identifying appropriate indications and contraindications. In the course of evaluating the multitude of studies, a set of formal recommendations have been propagated for the judicious use of these expensive growth factors. To prevent serious infection, the use of G- or GM-CSF is recommended in a subset of pediatric cancer patients shortly after receiving chemotherapy or a marrow transplant. Children with intensive chemotherapy (e.g., children with high risk ALL, NHL or metastatic neuroblastoma) seem to benefit from hematopoietic growth factors whereas it is not clear that this applies to children undergoing therapy for solid tumors such as rhabdomyosarcoma or Ewing's sarcoma. An exciting development is the use of G-CSF and GM-CSF to mobilize peripheral-blood progenitor cells. Future studies in pediatric cancer patients are clearly warranted to address several issues. Prospective clinical trials are still needed to define specific treatment groups who can benefit from growth factor support. In this regard, efforts must be directed at better defining the endpoints and in particular, assigning value to reduction in treatment of possible infectious complications, such as days in hospital, antibiotic usage and costs. In addition, randomized studies are required to evaluate the proper dosage and duration of therapy, which most likely will vary between groups, depending upon underlying malignancy and therapy given. In addition, combinations of different growth factors have to be tested, particularly if ex vivo expansion and the storage of hematopoietic stem cells are to be utilized in a wider spectrum of patients.

Background: Clinical practice guidelines are issued periodically by professional medical societies or committees to assist practitioners in clinical decision making. However, it is unclear whether such guidelines have any lasting impact on clinical practice., Objective: The purpose of this study was to assess the impact of the American Society of Clinical Oncology (ASCO) guidelines regarding use of hematopoietic colony-stimulating factors (CSF) on cancer care in a university hospital in Paris., Methods: The study was performed at Hĵpital Tenon, an 830-bed university hospital in Paris, in 1996 and 1997, both before and after the ASCO guidelines were implemented. The guidelines were first disseminated as a continuing medical education program and then actively implemented using a CSF prescription order form summarizing the guidelines. This form had to be used during the patient consultation and was sent to the Hĵpital Tenon pharmacy for CSF dispensation. Even if CSF use did not comply with the ASCO guidelines, the pharmacy filled the prescription. Seven other university hospitals in Paris, where the ASCO guidelines were not actively implemented, comprised the control group. The main outcome measure was the proportion of prescriptions in compliance with the 1996 update of the ASCO guidelines. Secondary outcome measures were the proportions of prescriptions in compliance with ASCO guidelines regarding primary prophylactic, secondary prophylactic, and therapeutic CSF administration., Results: Before implementation of the ASCO guidelines, CSF use in compliance with the guidelines was 39% (41/105) at the study site and 31% (16/51) at the control sites (P > 0.05). Six months after dissemination and implementation of the guidelines, the proportion of CSF prescriptions complying with ASCO guidelines increased significantly versus baseline (P = 0.003) in the study group, to 61% (50/82). However, even after the guidelines were implemented, compliance with guidelines on primary prophylactic CSF administration did not change significantly versus before implementation in the study group (12% [5/41] before implementation vs 6% [2/33] after implementation; P > 0.05)., Conclusions: The results suggest an association between the active implementation strategy (continuing medical education and CSF prescription reminder form) and physician compliance with the ASCO guidelines. Implementation of the ASCO guidelines appears to have had some impact on medical practice.

Aging is associated with a progressive decline in the functional reserve of multiple organ systems, which may lead to enhanced susceptibility to stress such as that caused by cancer chemotherapy. Myelodepression is the most common and the most commonly fatal complication of antineoplastic drug therapy and may represent a serious hindrance to the management of cancer in older individuals. This is already a common and pervasive problem and promises to become more so. Currently 60% of all neoplasms occur in persons aged 65 years and older, and this percentage is expected to increase as the population ages. This well-known phenomenon, sometimes referred to as squaring or the age pyramid, is caused by the combination of an increasing life expectancy and a decreasing birth rate. This article explores the use of hematopoietic growth factors in the older cancer patient after reviewing the influence of age on hemopoiesis and chemotherapy-related complications. The issue is examined in terms of effectiveness and cost. An outline of the assessment of the older cancer patient is provided at the end of the chapter as a frame of reference for clinical decisions.

Health-related quality of life (QOL) is poorest during the immediate post-transplantation period, but the impact of medical interventions during this period has not been studied. Colony-stimulating factors (CSFs), which are used to minimize short-term negative outcomes, might be expected to improve QOL; however, little is published about their impact on QOL during this period. We conducted a MEDLINE search to identify studies reporting on outcomes of stem cell transplantation (SCT) affected by the CSFs, mainly sargramostim and filgrastim. End points studied were: mucositis, incidence and type of infection, duration of hospitalization, time to myeloid engraftment, and quantity and quality of harvested cells. To impute the impact of CSFs on QOL post-SCT, we also reviewed the association between QOL and CSF outcomes in other circumstances. Data suggest that both CSFs improve QOL in the early autologous or allogeneic post-bone marrow transplantation period. Poor QOL caused by infection and increased length of hospital stay is expected to be improved by sargramostim. Time to myeloid engraftment, when negatively affecting QOL, is expected to be improved with both CSFs; however, the time to myeloid engraftment is consistently shorter with filgrastim. Current prospective trials designed to study the effects of CSFs in the immediate post-SCT period should collect QOL data.

Colony stimulating factors (CSFs), are essential for the regulation of the hematopoietic system and were developed by the pharmaceutical biotechnology industry in the early 1990s for the prevention of serious neutropenic complication after myelosuppressive chemotherapy. Both G-CSF and GM-CSF consistently lead to an increase in circulating white blood cells and a reduction in the incidence of fever and neutropenia after myelosuppressive chemotherapy in patients with solid tumors, hematologic malignancies, and those undergoing stem-cell transplantation. Their role in improving response rates to chemotherapy and overall survival is less clear.

Studies of primary prophylaxis of febrile neutropenia (FN) with recombinant human granulocyte colony-stimulating factor (rHu-G-CSF, filgrastim) administered to all patients starting their initial course of chemotherapy have demonstrated clinical effectiveness and an economic advantage in a wide range of settings. A recent meta-analysis confirmed the ability of filgrastim to reduce the risk of FN and documented infection in a variety of malignancies in both adults and children. The threshold risk for FN at which a cost saving is achieved by using filgrastim is inversely related to the daily cost of the drug and duration of hospitalization. Clinical practice guidelines for the use of filgrastim were developed based on these observations. Recent studies incorporating indirect institutional costs demonstrated that a cost saving can be achieved at substantially lower FN risk thresholds than previously estimated. Despite the demonstrated efficacy of filgrastim in primary prophylaxis, its value may be further increased by appropriately selecting patients and better understanding the importance of sustaining dose intensity in specific malignancies. Clinical prediction models capable of identifying individuals at high risk for neutropenic complications yield further reductions in FN risk thresholds and treatment costs in patients receiving cancer chemotherapy. These models also may be used to evaluate the cost-effectiveness or cost-efficiency of filgrastim. A clinical prediction model recently was presented and validated incorporating both baseline clinical characteristics as well as the results of the first cycle of chemotherapy in patients with early-stage breast cancer. A cost-effectiveness ratio of $34,297/year of life saved was estimated based on dose-response assumptions derived from a previously reported adjuvant breast cancer trial studying the impact of dose reduction on disease-free survival. The cost-effectiveness of filgrastim was evident over a wide range of clinical and cost assumptions. Clinical prediction models permit the rational and cost-effective identification of patients for filgrastim support. Existing clinical practice guidelines should be reevaluated in light of new information available on both the total costs associated with FN as well as the cost-effectiveness of these agents in patients receiving chemotherapy for sensitive and potentially curable malignancies.

Neutropenia is a common and often dose-limiting toxicity associated with chemotherapy One way to decrease the severity of this adverse event is to use colony-stimulating factors (CSFs) after chemotherapy. Colony-stimulating factors are relatively expensive agents, and most institutions limit their use. Unfortunately, it is difficult to predict which patients are likely to develop neutropenia. An improved ability to predict this situation might help institutions and clinicians determine which patients need CSFs as adjunctive therapy. The efficacy of CSFs and how they may affect patient outcomes are discussed. In addition, a primary literature review on the toxicity associated with chemotherapy regimens used for common cancers is summarized. Knowing the toxicity of individual regimens may help clinicians identify patients needing adjunctive therapy or less toxic regimens. Any action that helps reduce the occurrence, or severity, of neutropenia in patients receiving chemotherapy would be beneficial and enhance the patient's quality of life.

Much attention is being focused on biotherapy as the fourth modality of cancer treatment. The use of biotherapy in combination with chemotherapy presents a unique challenge to the nurse, particularly in the ambulatory setting. To provide quality care, nurses must have an understanding of the complexities of this therapy. An overview of biotherapy, including medications used, common side effects, and nursing considerations, is provided.

Optimal regimens for the treatment of invasive fungal infections have yet to be defined, and these life-threatening conditions are one of the leading causes of treatment failure in patients with cancer. A substantial body of preclinical work points in the direction of using cytokines as immunomodulators of the multiple deficiencies involved in the progression of fungal infections in neutropenic and nonneutropenic cancer patients. These deficiencies include not only the easily recognized deficiencies in cell quantity but also subtle deficiencies of cell function. Four cytokines (granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, and interferon gamma) show promise as adjuvant therapy for proven fungal infections in this setting, although clinical experience is still limited. As an additional approach, the concept of white blood cell transfusions has been revived by the use of granulocyte colony-stimulating factor and promises to be helpful in the setting of neutropenia.

We review the randomized trials published so far comparing the use of colony-stimulating factors (both G-CSF and GM-CSF) as adjunctive care in chemotherapy-induced neutropenic fever. With this treatment a slight one day reduction in duration of neutropenia under 500 neutrophils per mm3 is observed; this effect seems to be more important in prolonged neutropenias. The number of days with fever remain unchanged. No clear benefit expressed as clinical and quality of life improvement or economical saving is proved. According to these results, and as previous recommendation about the use of colony-stimulating factors pointed out, the indications for administration of such cytokines in neutropenic fever are restrictive and its use could be acceptable only in patients with poor prognostic factors.