NCCN Guidelines Insights: Hematopoietic Growth Factors, Version 1.2020.

Management of febrile neutropenia (FN) is an integral part of supportive care for patients undergoing cancer treatment. The NCCN Guidelines for Hematopoietic Growth Factors provide suggestions for appropriate evaluation, risk determination, prophylaxis, and management of FN. These NCCN Guidelines are intended to guide clinicians in the appropriate use of growth factors for select patients undergoing treatment of nonmyeloid malignancies. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines regarding the incorporation of newly FDA-approved granulocyte-colony stimulating factor biosimilars for the prevention and treatment of FN.

Medication overuse in oncology: current trends and future implications for patients and society.

The high cost of cancer care worldwide is largely attributable to rising drugs prices. Despite their high costs and potential toxic effects, anticancer treatments could be subject to overuse, which is defined as the provision of medical services that are more likely to harm than to benefit a patient. We found 30 studies documenting medication overuse in cancer, which included 16 examples of supportive medication overuse and 17 examples of antineoplastic medication overuse in oncology. Few specific agents have been assessed, and no studies investigated overuse of the most toxic or expensive medications currently used in cancer treatment. Although financial, psychological, or physical harms of medication overuse in cancer could be substantial, there is little published evidence addressing these harms, so their magnitude is unclear. Further research is needed to better quantify medication overuse, understand its implications, and help protect patients and the health-care system from overuse.

Economic impact on US Medicare of a new diagnosis of myelodysplastic syndromes and the incremental costs associated with blood transfusion need.

BACKGROUND: Recent retrospective studies suggest myelodysplastic syndromes (MDSs) are more common than previously recognized and patients who develop transfusional dependence may be at risk for increased comorbid complications. STUDY DESIGN AND METHODS: A retrospective review was undertaken of Medicare claims focusing on costs associated with patients with a new claim listing ICD-9-CM Diagnosis Code 238.7 in first quarter of 2003. Patients were followed until 2005 to assess resource use and costs. RESULTS: A total of 512 patients aged 65 years or more with newly diagnosed MDS were identified. Forty percent had received red blood cell transfusions between 2003 and 2005. During the 3-year follow-up, transfused patients experienced increased prevalence of cardiac diseases, dyspnea, and infections. Cumulative 3-year mean Medicare costs for MDS patients were $49,156. Transfused patients had greater use of hospital inpatient and outpatient services and incurred significantly higher mean costs than nontransfused patients ($88,824 vs. $29,519, p < 0.001). After adjustment for baseline characteristics and clinical complications, transfusion was independently associated with a 48% increase in monthly costs in addition to the cost of transfusion administration. CONCLUSION: MDS places a significant economic burden on the US Medicare system. MDS patients requiring transfusions experience higher prevalence of new comorbid conditions and incur significantly higher Medicare costs than nontransfused patients during the initial 3 years after diagnosis.

Are guidelines on use of colony-stimulating factors in solid cancers flawed?

In cancer care in Australia, we are very reliant on an array of expensive pharmaceuticals. Our use of these treatments is often based on multinational or foreign clinical studies. Oncologists are, to varying degrees, reliant on how the studies are interpreted by the writers of journal editorials, clinical guidelines and opinion pieces. Therefore it is important that these guidelines are balanced and evidence based. We have examined in detail one of the most influential and wide ranging clinical guidelines used in oncology, The American Society of Clinical Oncology (ASCO) 2006 Update of Recommendations for the use of White Blood Cell Factors: An Evidence-Based Clinical Practice Guideline. We have discussed in detail some of the controversial recommendations in this guideline and have exposed what we believe are some flaws in these recommendations. We would urge that we continue to be rigorous in our oversight of international research agendas and international clinical guidelines in the future.

A national French survey on the use of growth factors as adjuvant treatment of chronic hepatitis C.

UNLABELLED: We conducted a national retrospective survey on hospital practitioners to evaluate the magnitude of erythropoietin (EPO) or granulocyte colony-stimulating factor (G-CSF) prescriptions in patients treated for chronic hepatitis C. Four hundred seventy-one questionnaires were sent, and 274 practitioners (58.2%) responded. Forty-six percent of practitioners used EPO, and 31% used G-CSF. The total number of HCV-infected patients receiving antiviral therapy per year was estimated at 6,630 patients, of whom 8.8% and 4% received EPO and G-CSF, respectively. EPO-beta was the main EPO molecule prescribed at a median dose of 30,000 IU/wk (range: 2,000-80,000). The indications for prescribing EPO varied greatly, including "fragile patients" (34%), "low" Hb level (8-11 g/dL) (19%), "rapid decline" in Hb level (2-5 g/dL during the first month of therapy) (12%), and symptomatic anemic patients (7%). G-CSF was mainly prescribed for a "low" level of neutrophils ranging from 400 to 750 neutrophils/mm3. In multivariate analysis, independent predictors of EPO and G-CSF prescription were age of practitioner less than 45 years (EPO: OR = 1.96, P = 0.03; G-CSF: OR = 2.27, P = 0.004), practice in university hospital (EPO: OR = 5.89, P < 0.0001; G-CSF: OR = 2.39, P = 0.003), and the high number of CHC treated/year (EPO: OR = 6.18, P < 0.0001; G-CSF: OR = 2.58, P = 0.002). CONCLUSION: Our survey reveals an important rate of EPO and G-CSF prescriptions but with considerable disparity in the schedule of injections, the molecules used, and above all the indications. The suitable role of EPO and G-CSF as complements to HCV therapy urgently needs to be clarified.

Are prophylactic haematopoietic growth factors of value in the management of patients with aggressive non-Hodgkin's lymphoma?

Combination chemotherapy used to treat patients with aggressive non-Hodgkin's lymphoma is associated with neutropenia and subsequent infection, hospital admission and treatment delays. Haematopoietic growth factors (HGF) can prevent neutropenia and improve quality of life. We undertook a meta-analysis of six randomised and one nonrandomised trials to quantify the effect in previously untreated patients, and a simple cost-effectiveness analysis. The trials compared HGF plus chemotherapy with chemotherapy alone. In total, there were 779 patients aged between 15 and 82 years. Haematopoietic growth factors was associated with a statistically significant 44% reduction in the incidence of severe neutropenia (neutrophil count <0.5 x 10(9) l(-1)), a 60% reduction in the number of hospital admissions due to infection, an 80% reduction in the number of patients who had a treatment delay due to neutropenia and a 50% reduction in hospital stay. These data together with UK G-CSF drug costs were combined to develop a simple cost-effectiveness model, based on direct costs. Given the current cost of G-CSF, it would only be cost-effective among patients in which high rates of hospital stay due to neutropenia or infection are expected. Alternatively, if the cost could be reduced then all patients may be able to obtain the benefits. However, the evidence that prophylactic HGFs are clinically worthwhile is clear.

Cost effectiveness of myeloid growth factors in cancer chemotherapy.

Healthcare costs continue to rise and hospitalization represents the single largest component of direct medical costs associated with cancer care. Neutropenia and its complications, including febrile neutropenia (FN), remain the major dose-limiting toxicity of systemic cancer chemotherapy. Although under-reported, FN often occurs early in the course of chemotherapy and contributes substantially to the morbidity, mortality, and cost of treatment. The risk of FN and its complications are associated with treatment intensity, age, and various comorbidities. Myeloid growth factors (MGFs) have been used effectively in a variety of clinical settings to prevent or treat FN and assist patients receiving dose-intensive chemotherapy with or without stem cell support. A meta-analysis of the available randomized controlled trials has confirmed the efficacy of prophylactic MGFs. The cost of these agents, along with their large-scale clinical use, has prompted several economic investigations. Economic models based on measures of resource use derived from randomized controlled trials have provided estimates of expected treatment costs, along with FN risk threshold estimates for the cost-saving use of prophylactic MGF. Recent studies have demonstrated the potential value of targeting MGFs toward patients at greatest risk based on accurate and valid predictive models. Although an emerging role has become apparent for MGFs in managing adult leukemia and supporting high-dose therapy with stem cell transplantation in adults, their value in the support of children in these settings remains unclear. Continuing clinical and economic evaluation, along with an updating of clinical practice guidelines because of rapid technologic and clinical advances, is encouraged.

[Analysis of hematopoietic growth factor prescriptions in 19 french cancer centers]. / Analyse de la prescription de facteurs de croissance hématopoïétique dans 19 centres anticancéreux français. Groupe de pharmaciens de la Fédération nationale des centres de lutte contre le cancer.

Medical prescription of hematopoietic growth factors (HGF) was analysed in 19 anticancer french centers during 2 months. About 4% of anticancer chemotherapeutic cycles prescribed during this period were supported by HGF prescription. The mean duration of treatment was 8 days. Among the 755 collected prescriptions, two tumor localizations represented about 50% of the prescriptions: malignant non Hodgkin lymphomas and breast cancer. The other main localizations concerned adult or pediatric soft tissue sarcomas (18%), testicular cancer (7%) and gynecologic tumors (6%). The prescription for primary prophylaxis for febrile neutropenia remains the main use of HGF (44%). The respect of the guidelines established by the F|d|ration nationale des centres de lutte contre le cancer was analyzed. Overall, 66% of the prescriptions were in adequation with these guidelines. Whereas the consommation of HGF decreased in the 19 considered institutions, it did not reach a plateau and could decrease in institutions which are awaked to the international and national recommendations.

[Economic evaluation of the use of haematopoietic factors in managing malignant hemopathies]. / Evaluation économique de l'utilisation de facteurs de croissance hématopoïétiques dans la prise en charge des hémopathies malignes.

Economic evaluation of haematopoietic growth factors in the treatment of malignant hemopathies was undertaken along with clinical trials or retrospectives studies. The cost of the sole treatment was estimated to be 2,302 US$ per cycle. Cost-minimization analyses compared the cost of a treatment course (chemotherapy, bone marrow transplantation with and without haematopoietetic growth factors), and cost-effectiveness analyses estimated the cost per episode of averted febrile neutropenia. Results appear to be contradictory and do not allow definite conclusions about the existence of extra costs or of cost savings due to the introduction haematopoietetic growth factors, except in the case of filgrastim-mobilized peripheral blood progenitor cell transplantation.

[Hematopoietic growth factors in the treatment of malignant hemopathies]. / Les facteurs de croissance hématopoïétiques dans le traitement des hémopathies malignes.

The authors analyze the role of G-CSF and GM-CSF in hematological malignancies. These allow correction of drug-induced neutropenias and perhaps more importantly allow the increase of doses of chemotherapy to improve the antitumor effect, and permit the maintenance of full chemotherapy doses in elderly patients. They can also mobilize peripheral blood stem cells for autologous and recent allogeneic transplantation. They can be useful at low doses in correcting the spontaneous neutropenia of bone marrow failures. A specific antitumor effect, on the other hand, is extremely hypothetical. Erythropoietin by contrast has been disappointing in the treatment of anemia in spontaneous bone marrow failures. For the treatment of thrombocytopenias, preliminary results with thrombopoietin are encouraging. Combinations of growth factors will probably improve results obtained with one factor. However, in all cases the cost/benefit of growth factors will have to be strictly established.

Economic evaluation of new treatments: haematopoietic growth factors.

The clinical benefits of new healthcare interventions usually receive considerable attention, but their impact on the economic aspects of care provision are not so well considered. Among the issues that different audiences will want to see addressed are: how clinical benefits translate into resource use savings in practice; the extent to which clinical trial outcomes can be said to be representative or normal practice and the value of the economic impact to purchasers and providers. In this review we consider these elements using the haematopoietic growth factors as an example.

An economic model to assess the savings from a clinical application of haematopoietic growth factors.

Patients receiving chemotherapy frequently develop fever and neutropenia. Haematopoietic growth factors (HGFs) may decrease the duration of such episodes or may prevent a febrile neutropenic episode. In this study we introduce a Markov type economic model for the hospital which calculates all relevant direct costs and savings of HGF therapy and may support decisions on HGF administration. A distinction is made between patients receiving intensive and standard chemotherapy schedules. Our results indicate that HGFs can induce savings in intensive chemotherapy and standard chemotherapy following neutropenic fever. Prophylactic administration of HGF is cost-effective if the risk of infection is considerable. The risk of infection depends on underlying malignancy, corresponding treatment modalities and the health condition of the patient. The model is meant as an analytical framework and should be used carefully, as not all benefits (e.g. benefits to the patients) are considered. These benefits may be balanced against the additional costs or savings resulting from the economic model.

Economic outcomes associated with the use of hematopoietic growth factors.

The myeloid growth factors G-CSF and GM-CSF have had an impact on the supportive care of cancer patients as well as on the strategies utilized in chemotherapy dose intensification. Therapy with these factors has not been associated with improvements in survival, and hence an examination of their effects on economic outcomes is central to rational decision making regarding their use. Erythropoietin therapy has been shown to decrease transfusion requirements in anemic cancer patients undergoing chemotherapy and to improve the quality of life in responding patients. The available data on the economic outcomes associated with the use of these three factors in oncology practice are reviewed.

Hematopoietic growth factors. Defining the appropriate clinical role in multimodality cancer therapy.

Laboratory investigations have begun to elucidate the regulatory molecules that control the processes of blood cell growth and differentiation. Recombinant human colony-stimulating factors are examples of biotechnology-produced molecules that have epitomized the translation of such basic scientific investigation into therapeutic advances. Small cell lung cancer, a malignancy that is overall highly sensitive to aggressive myelosuppressive chemotherapy at initial presentation, has been used as a clinical model in which the activity of human colony-stimulating factors has been tested. In this article, the clinical applications of hematopoietic growth factors are reviewed in brief. The appropriate clinical use of these agents may allow novel therapeutic strategies to be developed in a research setting. Similarly, these agents have the potential to improve supportive care and improve certain clinical outcomes in the non-research clinical care of patients. Issues of cost of treatment are raised by these agents, but the true clinical value of hematopoietic growth factors needs to be studied more rigorously, with emphasis on quality of life and redistribution of care costs outside of hospitals before definitive statements can be made.

Economic analyses of clinical trials in cancer: are they helpful to policy makers?

Although clinical trials are being used to evaluate economic outcomes of new agents, there are methodological problems. Decisions based on these analyses may lead to inefficient use of medical resources. Randomized clinical trials provide important information on the efficacy of new pharmaceutical agents for cancer patients. Policy makers are likely to require both economic and clinical data in order to approve pharmaceuticals for widespread use. Clinical trials provide an opportunity to evaluate economic outcomes for new agents. However, the interpretation of economic analyses of clinical trials raises issues related to perspective of the investigators, study design, collection of data on resource utilization, and generalizability of data to other settings. In this paper, we review these issues and illustrate problems associated with analyses of economic data from a recent phase III trial of hematopoietic growth factors. Clinical results were similar in both Paris and New York in this phase III trial. However, economic results differed markedly between the hospital in Paris and the hospital in New York. While significant savings in terms of fewer days in the hospital and fewer laboratory tests and radiographs for the granulocyte-macrophage colony-stimulating factor (GM-CSF) patients were noted at the New York hospital, resource savings were not identified at the hospital in France. Caution must be used when reimbursement policies are based on economic analyses of clinical trials. Policy decisions must be based on studies that are carefully conducted, analyzed, and interpreted from both a clinical and an economic perspective.