losartan-potassium and Neoplasms

The tumor microenvironment is an important factor that can determine the success or failure of antitumor therapy. Cells of hematopoietic origin are one of the most important mediators of the tumor-host interaction and, depending on the cell type and functional state, exert pro- or antitumor effects in the tumor microenvironment or in adjacent tissues. Erythroid cells can be full members of the tumor microenvironment and exhibit immunoregulatory properties. Tumor growth is accompanied by the need to obtain growth factors and oxygen, which stimulates the appearance of the foci of extramedullary erythropoiesis. Tumor cells create conditions to maintain the long-term proliferation and viability of erythroid cells. In turn, tumor erythroid cells have a number of mechanisms to suppress the antitumor immune response. This review considers current data on the existence of erythroid cells in the tumor microenvironment, formation of angiogenic clusters, and creation of optimal conditions for tumor growth. Despite being the most important life-support function of the body, erythroid cells support tumor growth and do not work against it. The study of various signaling mechanisms linking tumor growth with the mobilization of erythroid cells and the phenotypic and functional differences between erythroid cells of different origin allows us to identify potential targets for immunotherapy.

Topics: Erythroid Cells; Erythropoiesis; Erythropoietin; Humans; Neoplasms; Signal Transduction; Tumor Microenvironment

Anemia is a common medical problem among patients with cancer and chronic kidney disease (CKD). Although anemia in patients with CKD is often treated with iron and erythropoietin-stimulating agents, there are controversies with regard to the use of erythropoietin-stimulating agents in cancer patients. In this article, we review the treatment of anemia in patients with cancer and CKD, in addition to summarizing the current guidelines in treatment of anemia in these patients.

Topics: Anemia; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Neoplasms; Renal Insufficiency, Chronic

Erythropoietin (EPO) is a glycoprotein cytokine known for its pleiotropic effects on various types of cells and tissues. EPO and its receptor EPOR trigger signaling cascades JAK2/STAT5, MAPK, and PI3K/AKT that are interconnected and irreplaceable for cell survival. In this article, we describe the role of the MAPK and PI3K/AKT signaling pathways during red blood cell formation as well as in non-hematopoietic tissues and tumor cells. Although the central framework of these pathways is similar for most of cell types, there are some stage-specific, tissue, and cell-lineage differences. We summarize the current state of research in this field, highlight the novel members of EPO-induced PI3K and MAPK signaling, and in this respect also the differences between erythroid and non-erythroid cells.

Topics: Animals; Cell Differentiation; Cell Proliferation; Cell Survival; Erythropoiesis; Erythropoietin; Humans; MAP Kinase Signaling System; Models, Biological; Neoplasms; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Receptors, Erythropoietin; Signal Transduction

Cancer and chemotherapy-induced anemia (CIA) is commonly encountered among patients undergoing active chemotherapy with or without radiation therapy. Its pathogenesis is complex and is often difficult to identify. Symptoms related to CIA may have a negative impact on quality of life and may influence treatment efficacy, disease progression and even survival. The recent major setback of erythropoietin-stimulating agents (ESAs) and the reluctance to transfuse cancer patients with mild and even moderate anemia, had resulted in significant under-treatment of CIA. The discovery of hepcidin and its role in iron homeostasis has revolutionized our understanding of the pathogenesis of iron deficiency and iron overload states. In the present review we examine the multifactorial pathogenesis of CIA, addressing the main mechanisms by which the tumor and immune system affect anemia. Additionally, we discuss the treatment options with more focus on the utilization of the new intravenous iron formulations for this indication.

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life

Erythropoietin (EPO), the primary cytokine of erythropoiesis, stimulates both proliferation and differentiation of erythroid progenitors and their maturation to red blood cells. Basal EPO levels maintain the optimum levels of circulating red blood cells. However, during hypoxia, EPO secretion and its expression is elevated drastically in renal interstitial fibroblasts, thereby increasing the number of erythroid progenitors and accelerating their differentiation to mature erythrocytes. A tight regulation of this pathway is therefore of paramount importance. The biological response to EPO is commenced through the involvement of its cognate receptor, EPOR. The receptor-ligand complex results in homodimerization and conformational changes, which trigger downstream signaling events and cause activation or inactivation of critical transcription factors that promote erythroid expansion. In recent years, recombinant human EPO (rEPO) has been widely used as a therapeutic tool to treat a number of anemias induced by infection, and chemotherapy for various cancers. However, several studies have uncovered a tumor promoting ability of EPO in man, which likely occurs through EPOR or alternative receptor(s). On the other hand, some studies have demonstrated a strong anticancer activity of EPO, although the mechanism still remains unclear. A thorough investigation of EPOR signaling could yield enhanced understanding of the pathobiology for a variety of disorders, as well as the potential novel therapeutic strategies. In this chapter, in addition to the clinical relevance of EPO/EPOR signaling, we review its anticancer efficacy within various tumor microenvironments.

Topics: Erythropoiesis; Erythropoietin; Health; Humans; Neoplasms; Receptors, Erythropoietin; Signal Transduction; Tumor Microenvironment

Anemia has and will continue to be a central theme in medicine particularly as clinicians are treating a burgeoning population of complex multi-organ system processes. As a result of multiple randomized controlled trials (RCTs), meta-analyses, and societal recommendations overly restrictive paradigms and under-administration of erythropoiesis stimulating agents (ESAs) have likely been followed by clinicians among all specialties.. A review of anemia in the context of chronic kidney disease, hematologic malignancies, and cancer is presented with focus on the establishment of ESAs as integral in the treatment of anemia. Multiple RCTs and meta-analyses studying the use of ESAs are presented with focus upon their application to clinical practice. A 'compendium' is proffered describing the evolution, establishment, and implications of ESA administration initially among those with CKD with rapid subsequent application to the Hematology-Oncology population of patients. Literature search methodologies have included MEDLINE (1985-2020), PubMed (1996-2020), Cochrane Central Trials (1985-2020), EMBASE (2000-2020), and ClinicalTrials.gov (2000-2020).. Upon evaluation of risks and benefits of ESAs focused opinion and commentary is made supporting more liberal use of these agents and strongly suggesting that the current underlying treatment 'pendulum' has perhaps shifted too far to the 'under-treatment' side in many cases.

Topics: Anemia; Blood Transfusion; Combined Modality Therapy; COVID-19; Epoetin Alfa; Erythropoietin; Expert Testimony; Forecasting; Guideline Adherence; Hematinics; Hematologic Neoplasms; Hematopoiesis; Humans; Iron; Medicine; Meta-Analysis as Topic; Multicenter Studies as Topic; Myocardial Ischemia; Neoplasms; Observational Studies as Topic; Pandemics; Practice Guidelines as Topic; Practice Patterns, Physicians'; Randomized Controlled Trials as Topic; Receptors, Erythropoietin; Renal Dialysis; Renal Insufficiency, Chronic; SARS-CoV-2; Venous Thromboembolism

Anemia is a common diagnosis in patients with cancer that may affect both quality of life and survival. Anemia in this patient population is often multifactorial, caused by direct effects of the malignancy, products secondary to the malignancy, the effects of treatment, or other factors. Therefore, a systematic approach is required to determine the true cause or causes of anemia. An appropriate workup of anemia in patients with cancer can lead to treatment with the potential to reduce transfusion needs and improve quality of life. The clinical benefit of these interventions for specific patients must be weighed against possible risk.

Topics: Anemia; Blood Transfusion; Erythropoietin; Humans; Neoplasms

The EU, the USA, and Japan account for the majority of biological pharmacotherapy use worldwide. Biosimilar regulatory approval pathways were authorised in the EU (2006), in Japan (2009), and in the USA (2015), to facilitate approval of biological drugs that are highly similar to reference products and to encourage market competition. Between 2007 and 2020, 33 biosimilars for oncology were approved by the European Medicines Agency (EMA), 16 by the US Food and Drug Administration (FDA), and ten by the Japan Pharmaceuticals and Medical Devices Agency (PMDA). Some of these approved applications were initially rejected because of manufacturing concerns (four of 36 [11%] with the EMA, seven of 16 [44%] with the FDA, none of ten for the PMDA). Median times from initial regulatory submission before approval of oncology biosimilars were 1·5 years (EMA), 1·3 years (FDA), and 0·9 years (PMDA). Pharmacists can substitute biosimilars for reference biologics in some EU countries, but not in the USA or Japan. US regulation prohibits substitution, unless the biosimilar has been approved as interchangeable, a designation not yet achieved for any biosimilar in the USA. Japan does not permit biosimilar substitution, as prescribers must include the product name on each prescription and that specific product must be given to the patient. Policy Reviews published in 2014 and 2016 in The Lancet Oncology focused on premarket and postmarket policies for oncology biosimilars before most of these drugs received regulatory approval. In this Policy Review from the Southern Network on Adverse Reactions, we identify factors preventing the effective launch of oncology biosimilars. Introduction to the market has been more challenging with therapeutic than for supportive care oncology biosimilars. Addressing region-specific competition barriers and educational needs would improve the regulatory approval process and market launches for these biologics, therefore expanding patient access to these products in the EU, the USA, and Japan.

Topics: Antineoplastic Agents, Immunological; Bevacizumab; Biosimilar Pharmaceuticals; Drug Approval; Drug Substitution; Erythropoietin; Europe; Filgrastim; Hematinics; Humans; Japan; Neoplasms; Patient Safety; Policy Making; Polyethylene Glycols; Risk Assessment; Rituximab; Trastuzumab; Treatment Outcome; United States; United States Food and Drug Administration

Erythropoietin (EPO) is a moonlighting protein since is ability to work as hormone, cytokine and growth factor. Its cardinal function is to regulate erythropoiesis in the bone marrow. However, EPO with his receptor EPOR are expressed also in non-hematopoietic tissues such as endothelium where they exert a protective function. Moreover, it is known EPO-EPOR pathway contribute to neovascularization in the angiogenic switch of tumor, but the mechanism is not completely established. In this article, after a brief introduction on tumor angiogenesis and description of classical and non-classical pro-angiogenic factors, we review the role of EPO in tumor angiogenesis highlighting the different mechanisms activated by it to promote tumor growth and progression. Finally, we analyze the controversy between the beneficial and the harmful effects of EPO. We suppose that the accurate characterization of EPO variants and their downstream pathways will allow to develop specific inhibition strategies to block only EPOR expressed by tumor cells without inducing signalling in hematopoietic cells to avoid side effects.

Topics: Animals; Cell Proliferation; Erythropoietin; Humans; Neoplasms; Neovascularization, Pathologic; Signal Transduction

Cognitive dysfunction is a challenging adverse effect of chemotherapy and radiotherapy that has limited treatment options. Clinical trials for proposed pharmacotherapeutic interventions to help manage these cognitive symptoms have had conflicting results and no standard of care has yet been established. Pharmacotherapeutic approaches for cancer therapy-induced cognitive symptoms include CNS stimulants (eg, methylphenidate and modafinil), medications used in patients with memory impairment (eg, donepezil, memantine, and ginkgo biloba), and bone marrow supporting agents (eg, erythropoietin). Whilst the beneficial effects of CNS stimulants have been mainly reported in children, efficacy in adults has been varied. Antidementia drugs have emerged as promising compounds in the management of cognitive dysfunction, but clinical experience of their use remains limited. Therefore, large clinical trials for these putative memory-enhancing drugs are needed to establish their clinical value in an oncology setting. Several clinical trials testing novel pharmacotherapeutic interventions for the management of cognitive dysfunction are ongoing, as well as numerous preclinical studies. With an increasing understanding of the molecular and cellular mechanisms underlying cognitive deficits in patients with cancer, novel treatment strategies are emerging.

Topics: Antineoplastic Agents; Central Nervous System Stimulants; Cholinesterase Inhibitors; Cognitive Dysfunction; Donepezil; Erythropoietin; Forecasting; Humans; Methylphenidate; Modafinil; Neoplasms; Radiotherapy

Our objective was to determine whether, compared with control interventions, pharmacologic interventions reduce the severity of fatigue in patients with cancer or recipients of hematopoietic stem-cell transplantation (hsct).. For a systematic review, we searched medline, embase, the Cochrane Central Register of Controlled Trials, cinahl, and Psychinfo for randomized trials of systemic pharmacologic interventions for the management of fatigue in patients with cancer or recipients of hsct. Two authors independently identified studies and abstracted data. Methodologic quality was assessed using the Cochrane Risk of Bias tool. The primary outcome was fatigue severity measured using various fatigue scales. Data were synthesized using random-effects models.. In the 117 included trials (19,819 patients), the pharmacologic agents used were erythropoietins (. Erythropoietin and methylphenidate significantly reduced fatigue severity in patients with cancer and in recipients of hsct. Concerns about the safety of those agents might limit their usefulness. Future research should identify effective interventions for fatigue that have minimal adverse effects.

Topics: Central Nervous System Stimulants; Erythropoietin; Fatigue; Hematopoietic Stem Cell Transplantation; Humans; Methylphenidate; Neoplasms; Severity of Illness Index

Kidney transplantation represents a renal replacement therapy for end-stage renal failure, with outcomes improving from year to year. With the improved survival prognosis, treatment of complications of chronic kidney disease after transplantation is becoming increasingly important. In particular, posttransplantation anemia (PTA) is often protracted, which could be related to a variety of factors, including the renal function status, graft rejection episodes, and infectious causes. PTA occurs in about 30-40% of transplant recipients, and is known to affect the function of the transplanted kidney as well as patient survival. Early PTA is associated with a risk of death and cardiovascular disorders, however, during this phase, priority is given to the appropriate maintenance of immunosuppression rather than to the treatment of anemia. Maintenance-phase PTA exerts a strong influence on the survival, prognosis of the transplanted kidney, quality of life, etc. Unlike the disease state and treatment of usual renal anemia, it has been suggested that PTA may possibly reflect the functional state of the transplanted kidney. Therefore, it has been suggested that proper renal function may be maintained by ensuring a normal hemoglobin level in kidney transplant recipients. Proper management of PTA could be expected to be associated with an improved prognosis of the transplanted kidney and improved patient survival in kidney transplant recipients. It is advisable to provide appropriate treatment by setting target levels in accordance with the dialysis vintage, primary disease, cardiovascular complications, and kidney transplant function and delineation of the transplant recipient characteristics.

Topics: Anemia; Anemia, Iron-Deficiency; Anti-Bacterial Agents; Antiviral Agents; Blood Transfusion; Erythropoietin; Graft Rejection; Hematinics; Hemolysis; Humans; Immunosuppressive Agents; Infections; Iron Compounds; Kidney Failure, Chronic; Kidney Transplantation; Neoplasms; Sex Factors; Time Factors

There is a growing interest for the discovery of new cancer-targeted delivery systems for drug delivery and diagnosis. A synopsis of the bibliographic data will be presented on bombesin, neurotensin, octreotide, Arg-Gly-Asp, luteinizing hormone-releasing hormone and other peptides. Many of them have reached the clinics for therapeutic or diagnostic purposes, and have been utilized as carriers of known cytotoxic agents such as doxorubicin, paclitaxel, cisplatin, methotrexate or dyes and radioisotopes. In our article, recent advances in the development of peptides as carriers of cytotoxic drugs or radiometals will be analyzed.

Topics: Animals; Antineoplastic Agents; Drug Carriers; Drug Delivery Systems; ErbB Receptors; Erythropoietin; Humans; Integrins; Neoplasms; Peptides; Receptors, Eph Family; Receptors, LHRH; Receptors, Neurotensin; Receptors, Somatostatin

Cell migration of normal cells is tightly regulated. However, tumor cells are exposed to a modified microenvironment that promotes cell migration. Invasive migration of tumor cells is stimulated by receptor tyrosine kinases (RTKs) and is regulated by growth factors. Erythropoietin (Epo) is a glycoprotein hormone that regulates erythropoiesis and is also known to be a potent chemotactic agent that induces cell migration by binding to its receptor (EpoR). Expression of EpoR has been documented in tumor cells, and the potential of Epo to induce cell migration has been explored. Stem cell factor (SCF) is a cytokine that synergizes the effects of Epo during erythropoiesis. SCF is the ligand of c-Kit, a member of the RTKs family. Molecular activity of RTKs is a primary stimulus of cell motility. Thus, expression of the SCF/c-Kit axis is associated with cell migration. In this chapter, we summarize data describing the potential effect of Epo/EpoR and SCF/c-Kit as promoters of cancer cell migration. We also integrate recent findings on molecular mechanisms of Epo/EpoR- and SCF/c-Kit-mediated migration described in various cancer models.

Topics: Cell Movement; Erythropoietin; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Stem Cell Factor

Erythropoietin (EPO) is the main hematopoietic hormone acting on progenitor red blood cells via stimulation of cell growth, differentiation, and anti-apoptosis. However, its receptor (EPOR) is also expressed in various non-hematopoietic tissues, including endothelium. EPO is a pleiotropic growth factor that exhibits growth stimulation and cell/tissue protection on numerous cells and tissues. In this article we review the angiogenesis potential of EPO on endothelial cells in heart, brain, and leg ischemia, as well as its role in retinopathy protection and tumor promotion. Furthermore, the effect of EPO on bone marrow and adipose tissue is also discussed.

Topics: Animals; Erythropoietin; Humans; Models, Biological; Neoplasms; Neovascularization, Physiologic; Organ Specificity

Chemotherapy-induced anaemia is frequent in cancer patients, with severity depending on the extent of the disease and intensity of treatment. Clinical guidelines recommend erythropoietin therapy to treat or prevent anaemia in some oncology/haematology patients being treated with chemotherapy. The patent expiry of the first-generation erythropoietins has led to the development of biosimilar products, i.e. therapeutic proteins exhibiting comparable quality, safety and efficacy to an existing reference biological medicine, the patent of which has expired. This review summarises the available data set supporting the use of one such biosimilar product, epoetin zeta (Retacrit™) in oncology/haematology. The body of evidence supporting the use of epoetin zeta continues to grow, with post-marketing clinical studies underway to evaluate its longer-term clinical efficacy and safety. Biosimilar medicines have the potential to offer cost savings to health care providers, with the assurance of ongoing risk management programmes to ensure patient safety.

Topics: Anemia; Biosimilar Pharmaceuticals; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Topics: Academies and Institutes; Anemia; Antineoplastic Agents; Blotting, Western; Consensus; Consensus Development Conferences, NIH as Topic; Drug Industry; Erythropoietin; Hematinics; Humans; Neoplasms; Observer Variation; Predictive Value of Tests; Receptors, Erythropoietin; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Risk Assessment; United States

Cancer patients frequently present with anaemia that may result from the direct or indirect effects of the tumor or its treatment. Anaemia is an independent adverse prognostic factor that exerts negative influence on quality of life and survival of cancer patients. Anaemia in malignant disorders often arises from an interplay of multiple aetiological and pathophysiologic mechanisms. Understanding these mechanisms will help the oncologist identify and treat specific causes of the anaemia thereby minimizing the use of blood transfusion, which is associated with many adverse effects. This paper reviewed the various aetiological and pathophysiologic mechanisms of anaemia in cancer patients including direct and indirect tumour effects that lead to reduced red cell production or increased red cell destruction via a myriad of mechanisms ranging from marrow infiltration and cancer-associated acute myelonecrosis to chronic inflammation, blood loss, iron, folate, vitamin B12 and other nutrients deficiencies, malignancy related renal injury, pure red cell aplasia, hypersplenism, haemophagocytic syndrome, red cell autoantibody production, non-immune red cell fragmentation and cytotoxic therapy-induced erythroid cell apoptosis and eryptosis. Hence anaemia in cancer patients is attributable to a wide spectrum of aetiological factors with multiple and sometimes overlapping pathophysiologic mechanisms. It is therefore necessary for the oncologists to thoroughly investigate all cases of anaemia with the aim of identifying the actual causative factors in order to offer more sustainable cause-specific treatment modalities that will minimize the use of blood transfusion with its attendant adverse effects.

Topics: Anemia; Bone Marrow Transplantation; Erythropoietin; Humans; Neoplasms; Quality of Life; Syndrome

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Erythropoietin; Female; Hematinics; Hepcidins; Humans; Male; Multicenter Studies as Topic; Neoplasms; Randomized Controlled Trials as Topic

The synthesis of recombinant human erythropoietin has marked a turning point in the treatment of anaemia secondary to chronic kidney disease. However, the potentially fatal cardio- and cerebrovascular complications of the intake of high-doses of ESAs (erythropoiesis-stimulating agents), such as those observed in athletes who resort to doping, reason out the ever-prevalent debate concerning the balance between the risks and benefits of ESA administration for therapeutic purposes. Hence, there is still a discussion as to what values haemoglobin should ideally be maintained at. Additional concerns arise in cancer patients due to the ability of erythropoietin to act as an angiogenic and, in general, as a cell growth factor, because this might favour the progression of neoplastic disease. We summarized the prominent points of the latest guidelines on the management of anaemia in nephropathic patients, also identifying the possible risks that may result from the tendency to aim at too low haemoglobin levels.

Topics: Anemia; Erythropoietin; Guidelines as Topic; Humans; Kidney Failure, Chronic; Neoplasms; Recombinant Proteins

Treatment of anemia remains an important component in the care of patients with nondialysis chronic kidney disease (CKD) and end-stage renal disease (ESRD). Erythropoietin-stimulating agents (ESAs) remains a key anemia treatment strategy in this patient population. However, anemia management in this group can become more complicated by prior or current history of malignancy. There has been a great deal of work both scientifically and in clinical trials in oncology that have revealed certain concerns and risks of ESA use in patients with cancer. In this review, we will bring together knowledge from nephrology and oncology literature to help nephrologists understand the implications for ESA treatment when CKD/ESRD is complicated by cancer. We also suggest an approach to the management of anemia in this patient group with active or previous malignancy.

Topics: Anemia; Contraindications; Erythropoietin; Female; Hematinics; Humans; Male; Neoplasms; Receptors, Erythropoietin; Renal Insufficiency, Chronic; Risk Factors

Cancer-related anemia (CRA) is due to multiple etiologies, including chemotherapy-induced myelosuppression, blood loss, functional iron deficiency, erythropoietin deficiency due to renal disease, marrow involvement with tumor as well as other factors. The most common treatment options for CRA include iron therapy, erythropoietic-stimulating agents (ESAs), and red cell transfusion. Safety concerns as well as restrictions and reimbursement issues surrounding ESA therapy for CRA have resulted in suboptimal treatment. Similarly, many clinicians are not familiar or comfortable using intravenous iron products to treat functional iron deficiency associated with CRA. This article summarizes our approach to treating CRA and discusses commonly encountered clinical scenarios for which current clinical guidelines do not apply.

Topics: Anemia; Erythrocyte Transfusion; Erythropoietin; Humans; Iron; Malnutrition; Neoplasms; Prevalence; Treatment Outcome

Anemia is frequently observed in cancer patients and can cause symptoms and result in red cell transfusions. The erythropoiesis stimulating agents (ESAs) have been shown to increase hemoglobin levels and reduce transfusion requirements in anemic subjects with cancer who are receiving chemotherapy. Initially, these benefits motivated broad use of the ESAs in oncology. Over the past 10 years, recognition of the adverse events that can be associated with ESA use in these patients, particularly venous thrombosis, has resulted in a rethinking of the issue of who are the correct candidates for treatment. Different health care systems have come to different conclusions based upon the available data and additional data are still being generated. This article will review the data concerning the safety of ESAs in cancer patients, including the results of additional trials published in the past 2 years. This will include a discussion of the potential of ESAs to impact tumor progression or survival. Thrombosis remains the most important and best documented adverse event associated with ESA therapy in oncology. The mechanism(s) through which ESAs alter thrombosis risk are still very poorly understood.

Topics: Anemia; Disease Progression; Erythropoietin; Hematinics; Humans; Neoplasms

Despite its high prevalence, anemia often does not receive proper clinical attention, and detection, evaluation, and management of iron deficiency anemia and iron-restricted erythropoiesis can possibly be an unmet medical need. A multidisciplinary panel of clinicians with expertise in anemia management convened and reviewed recent published data on prevalence, etiology, and health implications of anemia as well as current therapeutic options and available guidelines on management of anemia across various patient populations and made recommendations on the detection, diagnostic approach, and management of anemia. The available evidence confirms that the prevalence of anemia is high across all populations, especially in hospitalized patients. Anemia is associated with worse clinical outcomes including longer length of hospital stay, diminished quality of life, and increased risk of morbidity and mortality, and it is a modifiable risk factor of allogeneic blood transfusion with its own inherent risks. Iron deficiency is usually present in anemic patients. An algorithm for detection and management of anemia was discussed, which incorporated iron study (with primary emphasis on transferrin saturation), serum creatinine and glomerular filtration rate, and vitamin B12 and folic acid measurements. Management strategies included iron therapy (oral or intravenous), erythropoiesis-stimulating agents, and referral as needed.

Topics: Algorithms; Anemia, Iron-Deficiency; Critical Care; Erythropoiesis; Erythropoietin; Female; Ferritins; Heart Diseases; Hematology; Humans; Iron; Male; Neoplasms; Pregnancy; Pregnancy Complications, Hematologic; Quality of Life; Respiration Disorders; Treatment Outcome

Various studies highlight cognitive impairments in cancer patients. This paper proposes a review of longitudinal controlled studies evaluating the efficacy of interventions aiming to reduce these cognitive impairments. Longitudinal controlled studies evaluating the efficacy of interventions aiming to reduce cognitive impairments in adult cancer patients and published between 1993 and 2013 were identified, with the exception of studies that implied patients suffering from CNS tumor or metastasis. Pharmacological interventions (n = 11) suggested the positive impact of modafinil on memory and executive functions. Non-pharmacological interventions (n = 10) suggested the positive impact of cognitive revalidation and stimulation programs, psycho-education and meditation on several memory, attentional and executive objective as well as subjective functions. Non-pharmacological interventions show more significant cognitive benefits than pharmacological interventions. Some longitudinal controlled studies support the usefulness of interventions aiming to reduce cognitive impairments in cancer patients. Further studies should evaluate the effectiveness of programs combining technics aiming to reduce cognitive impairments and psychotherapeutic technics aiming to support patients' coping with illness.

Topics: Adult; Benzhydryl Compounds; Case-Control Studies; Central Nervous System Stimulants; Cognition; Cognition Disorders; Darbepoetin alfa; Donepezil; Erythropoietin; Estradiol; Executive Function; Female; Humans; Indans; Longitudinal Studies; Male; Meditation; Methylphenidate; Modafinil; Neoplasms; Piperidines

Anemia is a risk factor for increased postoperative morbidity and mortality. International guidelines, therefore, recommend preoperative diagnostic work up and causal treatment of anemia. Iron therapy, however, is suspected to negatively affect disease progression in patients with cancer-associated anemia. The objective of our systematic review was to assess the efficacy and safety of perioperative diagnosis and causal therapy of anemia, and to determine the effect of iron supplement on disease progression of cancer.We systematically searched multiple electronic databases. Two persons independently reviewed abstracts and full-text articles. We rated the risk of bias using the Cochrane Risk of Bias Tool and assessed the quality of the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Meta-Analyses were performed using the DerSimonian&Laird random effects method. Results indicate that preoperative therapy of anemia could reduce the need for blood transfusions (relative risk: 0,78; 95% confidence interval 0,61-1,02; number needed to treat: 6) For other patient-relevant outcomes the number of events were too small to detect clinically relevant differences. We could not find any evidence that iron supplements have an influence on the progression of tumors.

Topics: Anemia, Iron-Deficiency; Blood Transfusion; Disease Progression; Erythropoietin; Evidence-Based Medicine; Humans; Iron Compounds; Neoplasms; Perioperative Care; Prognosis; Randomized Controlled Trials as Topic

Erythropoiesis is finely regulated by two major cytokines, stem cell factor (SCF) and erythropoietin (Epo). Decrease levels of Epo result in caspase activation and erythroid progenitors apoptosis. However, normal erythroid cell maturation requests caspase activation and cleavage of various caspase substrates, except the erythroid transcription factor GATA-1, that is protected by interaction with the chaperone HSP70 in the nucleus. Therefore, molecular abnormalities associated with decrease of HSP70 expression in the nucleus may result in ineffective erythropoiesis characterized by apoptosis and impaired maturation of erythroid precursors. These findings open new potential targeted therapies for erythroid disorders.

Topics: Animals; Apoptosis; Caspases; Cell Differentiation; Cell Nucleus; Enzyme Activation; Erythroblasts; Erythrocyte Aging; Erythropoiesis; Erythropoietin; GATA1 Transcription Factor; HSP70 Heat-Shock Proteins; Humans; Myelodysplastic Syndromes; Neoplasm Proteins; Neoplasms; Protein Processing, Post-Translational; Proteolysis; Stem Cell Factor; Thalassemia

The 60% of tumors affected patients >65years of age and the future previsions are considering an amount of 70% after 2030. Elderly Patients presents multiple comorbidity, polipharmacy, and disability. Geriatric assessment helps physicians to take the best therapeutic decisions. Clinical conditions influence efficacy and tolerability of chemotherapy. Prophylactic use of G-CSF after chemotherapy lowers the rate and length of severe neutropenia , and decreases the episodes of febrile neutropenia. Anemia is a hematologic condition associated with ageing , but is frequently associated to concomitant chronic disease. Stem cells display increasing resistance to erythropoietin in the elderly patients and this is connected with the onset of pro-inflammatory cytokines characteristic of this age . Anemia is a common adverse event in cancer patients receiving chemotherapy. Several of the symptoms associated with anemia, such as fatigue, syncope, palpitations and dyspnea, reduce patient activity and have a profound effect on the quality of life [QOL]. Considering the unfit or frail status of elderly patient the at home use of peg-filgrastim and weekly or three weekly erythropoietin administration could be preferred for this setting of patients that lack of specialized nursing care or facilities. Further studies, considering the several differences in health organizations in vary countries, could be held to state the real impact of the biosimilars in comparison to the long acting originators in the reduction of costs in this group of patients.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Erythropoietin; Humans; Neoplasms

Erythropoietin (EPO) is a frequently prescribed drug for treatment of cancer-related and chemotherapy-induced anemia in cancer patients. Paradoxically, recent preclinical and clinical studies indicate that EPO could potentially accelerate tumor growth and jeopardize survival in cancer patients. In this review I critically discuss the current knowledge and broad biological functions of EPO in association with tumor growth, invasion, and angiogenesis. The emphasis is focused on discussing the complex interplay between EPO and other tumor-derived factors in angiogenesis, tumor growth, invasion, and metastasis. Understanding the multifarious functions of EPO and its reciprocal relation with other signaling pathways is crucial for developing more effective agents for cancer therapy and for minimizing risks for cancer patients.

Topics: Anemia; Animals; Erythropoietin; Humans; Neoplasms

Prior to the approval of the first erythropoiesis-stimulating agent (ESA) in the early 1990s, red blood cell transfusions were the primary means of treating severe chemotherapy-induced anemia (CIA), with little recourse for those with more mild forms of the condition. The introduction of the ESAs allowed treatment of mild-to-moderate CIA in patients with cancer. It has been a decade since darbepoetin alfa (DA), a second-generation ESA with a longer half-life, became available to patients with CIA.. We present a review of studies on DA in CIA, from its development through to the present day. Medline was searched for randomized clinical trials on DA. Additional trials and meta-analyses on ESAs were incorporated into this review when relevant.. The first publications on DA generally focused on optimal dosing, efficacy and tolerability. In these, it was shown that DA is an effective and well tolerated treatment option to achieve hematopoietic response, regardless of dosing interval. Subsequently, the focus shifted towards meta-analyses on survival data of all ESAs. These reported conflicting results regarding mortality and/or disease progression. However, guidelines for ESA use were updated and, when followed, these make ESAs a well tolerated and effective tool for managing CIA.. As the past decade has broadened our knowledge on the benefits and risks of CIA management, continued high-quality studies will help to optimize treatment with ESAs in order to maximize quality of life for these patients. The limitation of a literature review of this nature is the complete reliance on previously published research and the availability of these studies using the methodology outlined above.

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Darbepoetin alfa; Erythropoietin; Hematinics; Humans; Meta-Analysis as Topic; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Venous Thromboembolism

Erythropoiesis stimulating agents (ESAs) have been used widely for anemic patients, especially those on dialysis and with cancer. However, reports have suggested shorter survival in erythropoietin (EPO)-treated cancer patients. The purpose of this review is to summarize and evaluate critically the current information about ESA treatment and its possible association with mortality in cancer patients. The pendulum that initially swung in the direction of widespread ESA treatment, and then in the direction of no treatment, is swinging back toward a stable position. This review also provides tools to decide how and when to use ESAs safely, according to accepted guidelines.

Topics: Anemia; Clinical Trials as Topic; Erythropoietin; Hematinics; Humans; Medical Oncology; Neoplasms; Practice Guidelines as Topic; Societies, Medical; United States; United States Food and Drug Administration

Development of cytotoxic chemotherapy, which has several side effects, has resulted in the development in supportive care as well. Two families of novel drugs have spread in the care of chemotherapy induced anaemia: human recombinant erythropoietin and intravenous iron. They were praised for the decreased transfusion demand and the increased quality of life. However, if we read the literature critically, our enthusiasm should be decreased. New data show an unfavourable impact of erythropoietin on life expectancy. Furthermore, the health care policy has changed since the introduction of erythropoietin 25 years ago. Transfusion control has improved and cost awareness in health care has increased. Recommendations of the American Societies of Haematology and Clinical Oncology reflect on these considerations. Erythropoietin is not recommended in adjuvant settings. The choice between erythropoietin and transfusion is conferred to the clinician in case of the development of metastases. No sufficient scientific argument was found to support the use of intravenous iron supplementation.

Topics: Anemia, Iron-Deficiency; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Cost-Benefit Analysis; Epoetin Alfa; Erythropoietin; Health Policy; Hematinics; Humans; Hungary; Infusions, Intravenous; Iron Compounds; Life Expectancy; Medical Oncology; Neoplasms; Quality of Life; Recombinant Proteins

Advances in cancer treatment have greatly improved survival rates of children with cancer. However, these same chemotherapeutic or radiologic treatments may result in long-term health consequences. Anthracyclines, chemotherapeutic drugs commonly used to treat children with cancer, are known to be cardiotoxic, but the mechanism by which they induce cardiac damage is still not fully understood. A higher cumulative anthracycline dose and a younger age of diagnosis are only a few of the many risk factors that identify the children at increased risk of developing cardiotoxicity. While cardiotoxicity can develop at anytime, starting from treatment initiation and well into adulthood, identifying the best cardioprotective measures to minimize the long-term damage caused by anthracyclines in children is imperative. Dexrazoxane is the only known agent to date, that is associated with less cardiac dysfunction, without reducing the oncologic efficacy of the anthracycline doxorubicin in children. Given the serious long-term health consequences of cancer treatments on survivors of childhood cancers, it is essential to investigate new approaches to improving the safety of cancer treatments.

Topics: Adiponectin; Age Factors; Angiotensin-Converting Enzyme Inhibitors; Anthracyclines; Antibiotics, Antineoplastic; Antioxidants; Carbazoles; Cardiolipins; Cardiotonic Agents; Carvedilol; Doxorubicin; Erythropoietin; Heart; Heart Diseases; Humans; Lipid Peroxidation; Liposomes; Neoplasms; Piperazines; Propanolamines; Purines; Razoxane; Risk Factors; Sildenafil Citrate; Sulfones; Survivors; Ventricular Dysfunction, Left

Erythropoietin (Epo) is a low-molecular weight glycoprotein hormone stimulator of erythropoiesis synthesized in the fetal liver and in the adult kidney. Moreover, Epo is a pleiotropic cytokine that exerts diverse biological effects in non-hematopoietic tissues, and angiogenesis is indicated as one of its extra-hematopoietic functions. The involvement of Epo in angiogenesis may be considered as subset of its role in improving overall tissue oxygenation and of its anti-apoptotic role. In this context, Epo may be considered as an endogenous stimulator of vessel growth during tumor progression, and inhibition of Epo signaling might be suggested as a new antiangiogenic therapeutic approach. It is conceivable suppose that the effect of Epo is multifactorial, depending on the type of tumor and level of functionality of Epo receptor expression in tumor cells, as well as on other variables, such as hypoxic stress and degree of anemia.

Topics: Angiogenesis Inducing Agents; Animals; Erythropoietin; Humans; Neoplasms

The erythropoiesis-stimulating agents (ESAs) erythropoietin and darbepoetin prevent transfusions among chemotherapy-associated anemia patients. Clinical trials, meta-analyses, and guidelines identify mortality, tumor progression, and venous thromboembolism (VTE) risks with ESA administration in this setting. Product labels advise against administering ESAs with potentially curative chemotherapy (United States) or to conduct risk-benefit assessments (Europe/Canada). Since 2007, fewer chemotherapy-associated anemia patients in the United States and Europe receive ESAs. ESAs and the erythropoietin receptor agonist peginesatide prevent transfusions among chronic kidney disease (CKD) patients; clinical trials, guidelines, and meta-analyses demonstrate myocardial infarction, stroke, VTE, or mortality risks with ESAs targeting high hemoglobin levels. U.S. labels recommend administering ESAs or peginesatide at doses sufficient to prevent transfusions among dialysis CKD patients. For dialysis CKD patients, Canadian and European labels recommend targeting hemoglobin levels of 10 to 12 g/dL and 11 to 12 g/dL, respectively, with ESAs. ESA utilization for dialysis CKD patients has decreased in the United States.

Topics: Darbepoetin alfa; Erythropoietin; Humans; Neoplasms; Peptides; Renal Insufficiency, Chronic

For years, the treatment of chemotherapy-induced anemia (CIA) consisted of red blood cell transfusions. Major disadvantages of transfusions are their temporary effect and limitation to treatment of severe anemia. In an extensive clinical trial program in patients with CIA, darbepoetin alfa (DA) - a long-acting recombinant human erythropoietin - was proven to be very effective in reducing transfusion needs in patients developing CIA. The administration is suitable with most chemotherapy schemes. Caution is needed in patients with a history of thrombo-embolic events, as a slightly higher incidence of these events is noted in patients treated with darbepoetin alfa or erythropoietin substitution agents (ESAs) in general. In recent years, concerns have been raised about a potential negative influence of these agents on survival. In this respect, it is important to make the distinction between studies on the treatment of existing CIA versus treatment with ESAs outside this indication. On the other hand, it has always been assumed that transfusions were a completely safe treatment, but concerns about a potential negative effect on survival have been raised for transfusions as well. The safety concerns with DA and ESAs in general led to a pharmacovigilance program and an adaptation of the guidelines for treatment of CIA, focusing on treatment of moderate CIA but no longer on mild CIA. Now that the most recent safety data of the pharmacovigilance program of ESAs is almost completed, the clinical impact of the shift to the treatment of only moderate anemia is discussed in this review, which provides a critical view on the indications of DA and the benefit-risk assessment, in order to provide good supportive care without harm to the patient.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Erythrocyte Transfusion; Erythropoietin; Hematinics; Humans; Neoplasms; Practice Guidelines as Topic; Thromboembolism

Anaemia associated with cancer and cancer therapy is an important clinical factor in the treatment of malignant diseases. Therapeutic alternatives are recombinant human erythropoiesis stimulating agents (ESAs) and red blood cell transfusions.. To assess the effects of ESAs to either prevent or treat anaemia in cancer patients.. This is an update of a Cochrane review first published in 2004. We searched the Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE and other databases. Searches were done for the periods 01/1985 to 12/2001 for the first review, 1/2002 to 04/2005 for the first update and to November 2011 for the current update. We also contacted experts in the field and pharmaceutical companies.. Randomised controlled trials on managing anaemia in cancer patients receiving or not receiving anti-cancer therapy that compared the use of ESAs (plus transfusion if needed).. Several review authors assessed trial quality and extracted data. One review author assessed quality assessment and extracted data, a second review author checked for correctness.. This update of the systematic review includes a total of 91 trials with 20,102 participants. Use of ESAs significantly reduced the relative risk of red blood cell transfusions (risk ratio (RR) 0.65; 95% confidence interval (CI) 0.62 to 0.68, 70 trials, N = 16,093). On average, participants in the ESAs group received one unit of blood less than the control group (mean difference (MD) -0.98; 95% CI -1.17 to -0.78, 19 trials, N = 4,715). Haematological response was observed more often in participants receiving ESAs (RR 3.93; 95% CI 3.10 to 3.71, 31 trials, N = 6,413). There was suggestive evidence that ESAs may improve Quality of Life (QoL). There was strong evidence that ESAs increase mortality during active study period (hazard ratio (HR) 1.17; 95% CI 1.06 to 1.29, 70 trials, N = 15,935) and some evidence that ESAs decrease overall survival (HR 1.05; 95% CI 1.00 to 1.11, 78 trials, N = 19,003). The risk ratio for thromboembolic complications was increased in patients receiving ESAs compared to controls (RR 1.52, 95% CI 1.34 to 1.74; 57 trials, N = 15,498). ESAs may also increase the risk for hypertension (fixed-effect model: RR 1.30; 95% CI 1.08 to 1.56; random-effects model: RR 1.12; 95% CI 0.94 to 1.33, 31 trials, N = 7,228) and thrombocytopenia/haemorrhage (RR 1.21; 95% CI 1.04 to 1.42; 21 trials, N = 4,507). There was insufficient evidence to support an effect of ESA on tumour response (fixed-effect RR 1.02; 95% CI 0.98 to 1.06, 15 trials, N = 5,012).. ESAs reduce the need for red blood cell transfusions but increase the risk for thromboembolic events and deaths. There is suggestive evidence that ESAs may improve QoL. Whether and how ESAs affects tumour control remains uncertain. The increased risk of death and thromboembolic events should be balanced against the potential benefits of ESA treatment taking into account each patient's clinical circumstances and preferences. More data are needed for the effect of these drugs on quality of life and tumour progression. Further research is needed to clarify cellular and molecular mechanisms and pathways of the effects of ESAs on thrombogenesis and their potential effects on tumour growth.

Topics: Anemia; Cause of Death; Darbepoetin alfa; Erythrocyte Transfusion; Erythropoietin; Humans; Hypertension; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Thromboembolism

The essential biological role of erythropoietin (EPO) in maintaining erythrocyte mass has been well understood for many years. Although EPO is required for the maturation of red cells, it also has strong procoagulant effects on the vascular endothelium and platelets, which limit erythrocyte losses after hemorrhage. Like other members of the type 1 cytokine superfamily, EPO has multiple biological activities. For the past 10 years, multiple investigators have shown that EPO acts as a locally produced antagonist of proinflammatory cytokines that are generated by the innate immune response in response to infection, trauma, or metabolic stress. Specifically, EPO inhibits apoptosis of cells surrounding a locus of injury, reduces the influx of inflammatory cells, and recruits tissue-specific stem cells and endothelial progenitor cells. Available evidence suggests that these multiple, nonerythropoietic effects of EPO are mediated by a tissue protective receptor (TPR) that is distinct from the homodimeric receptor responsible for erythropoiesis. Notably, activation of the TPR requires a higher concentration of EPO than is needed for maximal erythropoiesis. Unfortunately, these higher concentrations of EPO also stimulate hematopoietic and procoagulant pathways, which can cause adverse effects and, therefore, potentially limit the clinical use of EPO for tissue protection. To circumvent these problems, the EPO molecule has been successfully modified in a variety of ways to interact only with the TPR. Early clinical experience has shown that these compounds appear to be safe, and proof of concept trials are ready to begin.

Topics: Animals; Apoptosis; Coagulants; Erythrocytes; Erythropoiesis; Erythropoietin; Hemorrhage; Humans; Hypoxia; Inflammation; Ischemia; Malaria, Cerebral; Neoplasms; Signal Transduction; Stem Cells; Thrombosis

Thromboembolic complications are the second leading cause of death in cancer patients. In contrast to the large body of literature on venous thromboembolism (VTE), relatively few reports have focused on the pathogenesis, incidence, management and outcomes of arterial thromboembolic events in patients with malignancy. The purpose of this article is to review the current literature on the etiology, mechanisms, and prognosis of arterial thromboembolic events in cancer patients and outline appropriate screening and management guidelines that may help lower the rates of morbidity and mortality related to these events.

Topics: Algorithms; Amyloidosis; Antineoplastic Agents; Antiphospholipid Syndrome; Erythropoietin; Female; Humans; Ischemia; Male; Myeloproliferative Disorders; Neoplasms; Neurofibromatosis 1; Peripheral Arterial Disease; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Radiation Injuries; Recombinant Proteins; Risk Factors; Thromboembolism; Thrombophilia; Transfusion Reaction

Recombinant human erythropoietin (rhEPO), the prototype erythropoiesis-stimulating agent developed in the 1980s, was among the first recombinant human proteins to be marketed for clinical use in the oncology setting. Anemia is a frequent concern in patients with cancer receiving myelosuppressive chemotherapy and the availability of rhEPO as an alternative to red blood cell transfusions to treat symptomatic anemia created excitement among clinicians, particularly during an era of mounting concern for transfusion-transmissible infections. Early studies of rhEPO for chemotherapy-induced anemia in patients with non-myeloid malignancies showed these agents improved hemoglobin levels and reduced transfusion rates. rhEPO therapy was reported to decrease fatigue and improve quality of life, although the magnitude and clinical meaningfulness of these effects have been debated. More recent clinical trials since 2003 linking rhEPO therapy to increased risk of tumor progression, thrombo-vascular events and mortality prompted implementation of use restrictions to minimize potential for harm. Scientific research to understand the basic mechanisms of the biologic effects of erythropoietin at the cellular receptor and signaling level has revealed pleiotropic cytokine effects extending beyond erythropoiesis regulation. The importance of erythropoietin receptor signaling in normal, non-erythroid tissues and in pre-clinical tumor models has been under intense investigation and scrutiny, as potential mechanisms of the adverse outcomes associated with rhEPO therapy have been debated. Further research will be required to clarify the complex interplay between the diverse hematopoietic and non-hematopoietic effects of erythropoietin in normal and malignant tissues and to optimize the clinical use of rhEPO in the supportive care of cancer patients.

Topics: Anemia; Animals; Antineoplastic Agents; Disease Progression; Erythropoietin; Humans; Neoplasms; Risk Factors

Highly publicized safety issues of medicinal products in recent years and the accompanying political pressure have forced both the US FDA and the European Medicines Agency (EMA) to implement stronger regulations concerning pharmacovigilance. These legislative changes demand more proactive risk management strategies of both pharmaceutical companies and regulators to characterize and minimize known and potential safety concerns. Concurrently, comprehensive surveillance systems are implemented, intended to identify and confirm adverse drug reactions, including the creation of large pharmacovigilance databases and the cooperation with epidemiological centres. Although the ambitions are high, not much is known about how effective all these measures are, or will be. In this review we analyse how the pharmacovigilance community has acted upon two adverse events associated with the use of erythropoiesis-stimulating agents: the sudden increase in pure red cell aplasia and the possible risk of tumour progression associated with these products. These incidents provide important insight for improving pharmacovigilance, but also pose new challenges for regulatory decision making.

Topics: Adverse Drug Reaction Reporting Systems; Animals; Disease Progression; Erythropoietin; Europe; Government Regulation; Humans; Neoplasms; Recombinant Proteins; Red-Cell Aplasia, Pure; United States

Erythropoietin (EPO), the main hemopoietic hormone synthesized by the kidney as well as by the liver in fetal life, is implicated in mammalian erythropoiesis. Production and secretion of EPO and the expression of its receptor (EPO-R) are regulated by tissue oxygenation. EPO and EPO-R, expressed in several tissues, exert pleiotropic activities and have different effects on nonhemopoietic cells. EPO is a cytokine with antiapoptotic activity and plays a potential neuroprotective and cardioprotective role against ischemia. EPO is also involved in angiogenesis, neurogenesis, and the immune response. EPO can prevent metabolic alterations, neuronal and vascular degeneration, and inflammatory cell activation. Consequently, EPO may be of therapeutic use for a variety of disorders. Many tumors express EPO and/or EPO-R, but the action of EPO on tumor cells remains controversial. It has been suggested that EPO promotes the proliferation and survival of cancer cells expressing EPO-R. On the other hand, other reports have concluded that EPO-R plays no role in tumor progression. This review provides a detailed insight into the nonhemopoietic role of EPO and its mechanism(s) of action which may lead to a better understanding of its potential therapeutic value in diverse clinical settings.

Topics: Animals; Antineoplastic Agents; Erythropoiesis; Erythropoietin; Humans; Kidney; Neoplasms; Neovascularization, Pathologic; Receptors, Erythropoietin

Over the past few decades, understanding of the physiologic function of erythropoietin (EPO) has evolved significantly. EPO binds to erythropoietin receptors (EPOR), initiating signaling that stimulates growth, inhibits apoptosis, and induces the differentiation of erythroid progenitors to increase red blood cell mass. EPO has additionally been shown to exert tissue-protective effects on multiple tissues, suggesting a pleiotropic mechanism of action. Erythropoiesis-stimulating agents (ESA) are used clinically for treating cancer-related anemia [chemotherapy-induced anemia (CIA)]. Recent clinical trials have reported increased adverse events and/or reduced survival in ESA-treated cancer patients receiving chemotherapy, potentially related to EPO-induced cancer progression. Signaling pathways downstream of EPO/EPOR have been shown to influence numerous cellular functions in both normal and tumor cells, including proliferation, apoptosis, and drug resistance. Some studies have reported effects on proliferation, reduced chemotherapy efficacy, reduction of apoptosis, and resistance to selective therapies on cancer cell lines, whereas others have shown null effects. In addition, newer targeted cancer therapies that are directed toward specific signaling pathways may be antagonized by ESAs. This molecular interplay between anticancer agents and potential survival signals triggered by ESAs may have been underestimated and may contribute toward decreased survival seen in certain trials. As more targeted anticancer therapies become available, these types of interactions may mitigate therapeutic efficacy by allowing tumor cells to acquire drug resistance. Therefore, a more complete understanding of the complex pathways involved will allow for the rational use of ESAs for the safe treatment of CIA in oncology patients.

Topics: Anemia; Antineoplastic Agents; Disease Progression; Drug Interactions; Erythropoietin; Hematinics; Humans; Neoplasms; Signal Transduction

Erythropoietin is a glycoprotein predominantly produced in the kidney. It is an essential regulator of erythropoiesis in the bone marrow. Although cancer-associated anemia is caused by multiple factors, recombinant erythropoietin (rhuEpo) was widely used to treat and prevent this condition. Several clinical studies showed that the use of rhuEpo results in an efficient reduction of red blood cell transfusions in cancer-associated anemia. However, over the past twenty years, Epo and its receptor EpoR were found to be expressed also outside the hematopoietic system and in malignant tumors. This led to a discussion concerning potential risks associated with the application of erythropoiesis-stimulating agents in oncology.

Topics: Anemia; Erythrocyte Transfusion; Erythropoietin; Humans; Neoplasms; Risk Factors

The in vitro production of recombinant protein molecules has fostered a tremendous interest in their clinical application for treatment and support of cancer patients. Therapeutic proteins include monoclonal antibodies, interferons, and haematopoietic growth factors. Clinically established monoclonal antibodies include rituximab (targeting CD20-positive B-cell lymphomas), trastuzumab (active in HER-2 breast and gastric cancer), and bevacizumab (blocking tumor-induced angiogenesis through blockade of vascular-endothelial growth factor and its receptor). Interferons have lost much of their initial appeal, since equally or more effective treatments with more pleasant side effects have become available, for example in chronic myelogenous leukaemia or hairy cell leukaemia. The value of recombinant growth factors, notably granulocyte colony stimulating factor (G-CSF) and erythropoietin is rather in the field of supportive care than in targeted anti-cancer therapy. Adequately powered clinical phase III trials are essential to estimate the true therapeutic impact of these expensive compounds, with appropriate selection of clinically relevant endpoints and sufficient follow-up. Monoclonal antibodies, interferons, and growth factors must also, and increasingly so, be subjected to close scrutiny by appropriate cost-effectiveness analyses to ensure that their use results in good value for money. With these caveats and under the condition of their judicious clinical use, recombinant proteins have greatly enriched the therapeutic armamentarium in clinical oncology, and their importance is likely to grow even further.

Topics: Antibodies, Monoclonal; Antineoplastic Agents; Erythropoietin; Granulocyte Colony-Stimulating Factor; Humans; Intercellular Signaling Peptides and Proteins; Interferons; Leukemia; Lymphoma; Neoplasms; Recombinant Proteins

Erythropoietin (Epo) may be considered as an endogenous stimulator of vessel growth during tumor progression through an autocrine and/or paracrine loop. The vascular effects of Epo would be relevant in tumor angiogenesis and the negative effect of Epo on tumor growth may be aggravated by its angiogenic activity. The mechanism of tumor growth in the context of Epo is not completely clarified, and it is still not clear whether there is a direct effect of Epo in tumor cells as opposed to exogenous effect on angiogenesis. It is also possible that the effect of Epo is multifactorial depending on the type of tumor and level of functionality of Epo receptor expression in tumor cells, as well other variables such as hypoxic stress, degree of anemia, chemotherapy, radiotherapy of surgical intervention.

Topics: Animals; Disease Progression; Erythropoietin; Gene Expression Regulation, Neoplastic; Humans; Membrane Proteins; Neoplasms; Neovascularization, Pathologic; Vascular Endothelial Growth Factor A

The production of haematopoietic cells is under the tight control of a group of haematopoietic cytokines. Each cytokine has multiple actions mediated by receptors whose cytoplasmic domains contain specialized regions initiating survival, proliferation, differentiation commitment, maturation and functional activation. Granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO), and thrombopoiesis-stimulating agents are in routine clinical use to stimulate cell production and in total have been used in the management of many millions of patients. G-CSF regulates neutrophil production to maintain blood neutrophil counts in the normal range. G-CSF is used to prevent febrile neutropenia or to increase dose-density in chemotherapy regimens. Despite consistently showing a shorter duration of neutropenia, multiple prospective randomized trials have documented only modest clinical benefit. A clinical advantage of dose-dense chemotherapy has been shown only in specific chemotherapy regimens. Professional recommendations tailor the use of CSFs to patients with a high risk of adverse outcome of febrile neutropenia. EPO was used to prevent anaemia requiring red blood cell transfusion. However, recent studies strongly suggest a negative overall effect on mortality, without a plausible biological explanation. It is now proposed that its use should be restricted to patients in clinical trials. Thrombopoiesis-stimulating agents have only been recently introduced into the market for splenectomized and non-splenectomized patients with immune thrombocytopenic purpura, a rare disease. Before widely used in other conditions such as chemotherapy-induced thrombocytopenia, the lessons learned from the example of G-CSF and EPO should be taken seriously.

Topics: Clinical Trials as Topic; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hematopoiesis; Humans; Medical Oncology; Neoplasms; Recombinant Proteins; Thrombopoietin

Oxidative stress significantly impacts multiple cellular pathways that can lead to the initiation and progression of varied disorders throughout the body. It therefore becomes imperative to elucidate the components and function of novel therapeutic strategies against oxidative stress to further clinical diagnosis and care. In particular, both the growth factor and cytokine erythropoietin (EPO) and members of the mammalian forkhead transcription factors of the O class (FoxOs) may offer the greatest promise for new treatment regimens since these agents and the cellular pathways they oversee cover a range of critical functions that directly influence progenitor cell development, cell survival and degeneration, metabolism, immune function, and cancer cell invasion. Furthermore, both EPO and FoxOs function not only as therapeutic targets, but also as biomarkers of disease onset and progression, since their cellular pathways are closely linked and overlap with several unique signal transduction pathways. However, biological outcome with EPO and FoxOs may sometimes be both unexpected and undesirable that can raise caution for these agents and warrant further investigations. Here we present the exciting as well as complicated role EPO and FoxOs possess to uncover the benefits as well as the risks of these agents for cell biology and clinical care in processes that range from stem cell development to uncontrolled cellular proliferation.

Topics: Animals; Biomarkers; Cell Proliferation; Cell Survival; Erythropoietin; Forkhead Box Protein O1; Forkhead Box Protein O3; Forkhead Transcription Factors; Humans; Immune System; Neoplasms; Oxidative Stress; Receptors, Erythropoietin; Signal Transduction; Stem Cells

Recombinant human erythropoietin (rhEPO) has been used clinically to alleviate cancer- and chemotherapy-related anemia. However, recent clinical trials have reported that rhEPO also may adversely impact disease progression and survival. The expression of functional EPO receptors (EPOR) has been demonstrated in many human cancer cells where, at least in vitro, rhEPO can stimulate cell growth and survival and may induce resistance to selected therapies. Responses to rhEPO measured by alterations in tumor cell growth or survival, activation of signaling pathways or modulation of sensitivity to anticancer agents are variable. Both methodological and inherent biological issues underlie the differential cell responses, including reported difficulties in EPOR protein detection, potential involvement of EPOR isoforms or of cytoplasmic EPOR, possible differential structure and/or binding affinities of hematopoietic versus non-hematopoietic cell EPOR, possible aberrant regulation of EPOR activity, and a functional EPO/EPOR autocrine/paracrine loop. The modulation by rhEPO of tumor cell response to anticancer agents is coincident with modulation of multiple signaling pathways, BCL-2 family proteins, caspases and NFkB. The molecular interplay of pro-survival and pro-death signals, triggered by EPO and/or by anticancer agents, is multifactorial and tightly coordinated. Expression microarray analysis may prove critical for deciphering this potentially novel network and its broad spectrum of genes and proteins.

Topics: Animals; Cell Proliferation; Cell Survival; Drug Resistance, Neoplasm; Erythropoietin; Humans; Neoplasms; Receptors, Erythropoietin; Signal Transduction

Anaemia is a frequent complication of cancer. Recently, some concerns have appeared regarding the safety of erythropoiesis-stimulating agents (ESAs) for the treatment of anaemia in cancer patients. The current review will analyse the main arguments in favour of erythropoietin (EPO), as well as those against EPO in chemotherapy-induced anaemia and in cancer-related anaemia. The principal concerns are tumour progression, increased mortality and the risk of venous thromboembolic events (VTEs). Recent meta-analyses have come to divergent conclusions.. Several meta-analyses have reviewed the data regarding VTEs, EPO receptors on tumours and tumour progression as well as mortality.. As of now, ESAs should only be used within the indications as given in the various guidelines.

Topics: Anemia; Disease Progression; Erythropoietin; Hematinics; Humans; Hypertension; Neoplasms; Red-Cell Aplasia, Pure; Risk Assessment; Seizures

Erythropoiesis stimulating proteins are approved for chemotherapy-induced anemia. Treatment with ESPs results in an increase in hemoglobin in 60 - 70 % of patients and in a significant reduction in transfusion need. A marked increase in hemoglobin levels usually is associated with an improvement in quality of life. Relevant side effects include an increase in thromboembolic complications and, in case of use in unapproved indications, a minimally increased mortality, which is not seen when ESPs are used in the approved indications. Treatment with ESPs should be initiated at hemoglobin levels < 100 g/l and a target level of 120 g/l should not be exceeded.

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Hematinics; Humans; Neoplasms; Proteins; Recombinant Proteins

This is an updated version of the original Cochrane review published in issue 1 2008 (Minton 2008). Cancer-related fatigue (CRF) is common, under-recognised and difficult to treat. There have been studies looking at drug interventions to improve CRF but results have been conflicting depending on the population studied and outcome measures used. No previous reviews of this topic have been exhaustive or have synthesised all available data.. To assess the efficacy of drugs for the management of CRF.. We searched the Cochrane Central Register of Controlled Trials (from Issue 2 2007) MEDLINE and EMBASE from January 2007 to October 2009 and a selection of cancer journals. We searched references of identified articles and contacted authors to obtain unreported data.. Studies were included in the review if they 1) assessed drug therapy for the management of CRF compared to placebo, usual care or a non-pharmacological intervention in 2) randomised controlled trials (RCT) of 3) adult patients with a clinical diagnosis of cancer.. Two review authors independently assessed trial quality and extracted data. Meta-analyses were performed on different drug classes using continuous variable data.. Fifty studies met the inclusion criteria. Six additional studies were identified since the original review. Only 31 of these studies involving 7104 participants were judged to have used a sufficiently robust measure of fatigue and thus were deemed suitable for detailed analysis. The drugs were still analysed by class (psychostimulants; haemopoietic growth factors; antidepressants and progestational steroids). Methylphenidate showed a small but significant improvement in fatigue over placebo (Z = 2.83; P = 0.005). Since the publication of the original review increased safety concerns have been raised regarding erythropoietin and this cannot now be recommended in practice.There was a very high degree of statistical and clinical heterogeneity in the trials and the reasons for this are discussed.. There is increasing evidence that psychostimulant trials provide evidence for improvement in CRF at a clinically meaningful level. There is still a requirement for a large scale RCT of methylphenidate to confirm the preliminary results from this review. There is new safety data which indicates that the haemopoietic growth factors are associated with increased adverse outcomes. These drugs can no longer be recommended in the treatment of CRF. Readers of the first review should re-read the document in full.

Topics: Adult; Antidepressive Agents; Central Nervous System Stimulants; Darbepoetin alfa; Erythropoietin; Fatigue; Hematinics; Humans; Methylphenidate; Neoplasms; Progestins; Randomized Controlled Trials as Topic

After the patents of biopharmaceuticals have expired, based on specific regulatory approval pathways copied products ("biosimilars" or "follow-on biologics") have been launched in the EU. This article summarizes experiences with hematopoietic medicines, namely the epoetins (two biosimilars traded under five different brand names) and the filgrastims (two biosimilars, six brand names). Physicians and pharmacists should be familiar with the legal and pharmacological specialities of biosimilars: The production process can differ from that of the original, clinical indications can be extrapolated, glycoproteins contain varying isoforms, the formulation may differ from the original, and biopharmaceuticals are potentially immunogenic. Only on proof of quality, efficacy and safety, biosimilars are a viable option because of their lower costs.

Topics: Anemia; Antineoplastic Agents; Biological Products; Chronic Disease; Drug Utilization; Erythropoietin; European Union; Filgrastim; Granulocyte Colony-Stimulating Factor; Guidelines as Topic; Humans; Isoantibodies; Kidney Diseases; Legislation, Drug; Marketing; Neoplasms; Patents as Topic; Polyethylene Glycols; Quality Control; Recombinant Proteins; Red-Cell Aplasia, Pure; Therapeutic Equivalency; World Health Organization

Inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), among others, play a major role in the pathophysiology of anemia in the cancer patient not only through complex mechanisms of the purely inflammatory situation but also through genetic regulatory aspects of erythropoiesis via GATA-1 and GATA-2, and other factors. In terms of therapy, iron is used more and more; the late side effects of transfusions are not really understood and the recent controversy regarding erythropoietin usage has resulted in regulatory authorities and scientific societies providing several recommendations and guidelines. These various aspects are addressed herein.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Erythropoietin; Humans; Neoplasms

To update American Society of Hematology/American Society of Clinical Oncology recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer.. An Update Committee reviewed data published between January 2007 and January 2010. MEDLINE and the Cochrane Library were searched.. The literature search yielded one new individual patient data analysis and four literature-based meta-analyses, two systematic reviews, and 13 publications reporting new results from randomized controlled trials not included in prior or new reviews.. For patients undergoing myelosuppressive chemotherapy who have a hemoglobin (Hb) level less than 10 g/dL, the Update Committee recommends that clinicians discuss potential harms (eg, thromboembolism, shorter survival) and benefits (eg, decreased transfusions) of ESAs and compare these with potential harms (eg, serious infections, immune-mediated adverse reactions) and benefits (eg, rapid Hb improvement) of RBC transfusions. Individual preferences for assumed risk should contribute to shared decisions on managing chemotherapy-induced anemia. The Committee cautions against ESA use under other circumstances. If used, ESAs should be administered at the lowest dose possible and should increase Hb to the lowest concentration possible to avoid transfusions. Available evidence does not identify Hb levels ≥ 10 g/dL either as thresholds for initiating treatment or as targets for ESA therapy. Starting doses and dose modifications after response or nonresponse should follow US Food and Drug Administration-approved labeling. ESAs should be discontinued after 6 to 8 weeks in nonresponders. ESAs should be avoided in patients with cancer not receiving concurrent chemotherapy, except for those with lower risk myelodysplastic syndromes. Caution should be exercised when using ESAs with chemotherapeutic agents in diseases associated with increased risk of thromboembolic complications. Table 1 lists detailed recommendations.

Topics: Adult; Anemia; Darbepoetin alfa; Disease Progression; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

To update American Society of Clinical Oncology/American Society of Hematology recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer.. An Update Committee reviewed data published between January 2007 and January 2010. MEDLINE and the Cochrane Library were searched.. The literature search yielded one new individual patient data analysis and four literature-based meta-analyses, two systematic reviews, and 13 publications reporting new results from randomized controlled trials not included in prior or new reviews.. For patients undergoing myelosuppressive chemotherapy who have a hemoglobin (Hb) level less than 10 g/dL, the Update Committee recommends that clinicians discuss potential harms (eg, thromboembolism, shorter survival) and benefits (eg, decreased transfusions) of ESAs and compare these with potential harms (eg, serious infections, immune-mediated adverse reactions) and benefits (eg, rapid Hb improvement) of RBC transfusions. Individual preferences for assumed risk should contribute to shared decisions on managing chemotherapy-induced anemia. The Committee cautions against ESA use under other circumstances. If used, ESAs should be administered at the lowest dose possible and should increase Hb to the lowest concentration possible to avoid transfusions. Available evidence does not identify Hb levels ≥ 10 g/dL either as thresholds for initiating treatment or as targets for ESA therapy. Starting doses and dose modifications after response or nonresponse should follow US Food and Drug Administration-approved labeling. ESAs should be discontinued after 6 to 8 weeks in nonresponders. ESAs should be avoided in patients with cancer not receiving concurrent chemotherapy, except for those with lower risk myelodysplastic syndromes. Caution should be exercised when using ESAs with chemotherapeutic agents in diseases associated with increased risk of thromboembolic complications. Table 1 lists detailed recommendations.

Topics: Adult; Anemia; Darbepoetin alfa; Disease Progression; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

Anemia in cancer patients is common and often associated with decreased survival and quality-of-life scores. The introduction of erythropoiesis-stimulating agents (ESAs) for the treatment of anemia in patients with solid tumors and nonmyeloid malignancies in the 1990s has proved an important alternative to red blood cell transfusions. ESAs have been consistently shown to increase hemoglobin levels and reduce transfusion requirements in anemic cancer patients whilst also being associated with improvements in quality of life. Several recent studies, however, have raised concerns about the safety of ESAs with regards to an increased number of thrombo-embolic events, decreased on-study survival and possible effects of ESAs on tumor progression. This has led to a reappraisal of the role of ESAs in the treatment of anemic cancer patients. It remains generally accepted that, if used within current guidelines and labeling recommendations, ESAs can still be considered safe in patients receiving chemotherapy once individual risks are balanced against possible benefits.

Topics: Anemia; Disease Progression; Erythropoietin; Hematinics; Humans; Iron; Neoplasms; Prognosis; Quality of Life; Recombinant Proteins; Venous Thromboembolism

Therapy with erythropoiesis-stimulating agents (ESAs) is associated with well-documented benefits to anemic cancer patients undergoing chemotherapy, most importantly a reduction in the likelihood of needing red cell transfusions. One challenge in supportive cancer care is a relative resistance to ESAs, requiring high doses with a significant rate of nonresponse. Recent advances in our understanding of iron metabolism in patients with chronic illness and the results of clinical trials indicate that parenteral iron improves ESA response in this setting. Another issue is the safety of ESA treatment in cancer patients. There is an increased risk of venous thrombosis that must be considered in clinical decision making. There are also recent data raising concerns that ESAs may enhance tumor progression or decrease patient survival. Although the preponderance of the data suggests that ESAs do not alter survival when used to treat chemotherapy-induced anemia, large well-controlled trials addressing this issue are needed.

Topics: Anemia; Cell Hypoxia; Disease Progression; Drug Resistance; Erythropoietin; Hematinics; Humans; Neoplasm Metastasis; Neoplasms

The Standards, Options, and Recommendations (SOR) project undertaken by the French National Federation of Cancer Centers (FNCLCC) to develop and disseminate clinical practice guidelines in oncology has now been taken over by the French National Cancer Institute. In 2007, the SOR updated the information related to the use of erythropoiesis-stimulating agents (ESA) in anemic children with cancer. Updates were based on a review of the most reliable scientific data available, followed by critical appraisal by a multidisciplinary group of experts and validation by independent experts. The literature review identified four randomized trials likely to provide reliable new information on the use of ESA in children. This review confirmed four points: treatment increases hemoglobin levels and decreases the need for blood transfusions; no quality-of-life and no survival benefit has been demonstrated; treatment does not seem associated with significantly more side effects; impact on thromboembolic events and patient quality of life remains unclear. The main result of the study was the elaboration of a new standard of care unavailable at the time of the 2003 version. Systematic administration of ESA is not recommended for the prevention or treatment of anemia in pediatric cancer patients. However, treatment decision must be made on a case-by-case basis and, when treatment is considered, the intravenous route must be preferred. The full French document is available at www.sor-cancer.fr.

Topics: Anemia; Animals; Cell Proliferation; Child; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Injections, Intravenous; Neoplasms; Practice Guidelines as Topic; Quality of Life; Receptors, Erythropoietin; Recombinant Proteins; Survival Rate

Topics: Adrenal Cortex Hormones; Angiogenesis Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Breast Neoplasms; Clinical Trials as Topic; Erythropoietin; Female; Humans; Models, Biological; Multiple Myeloma; Myeloproliferative Disorders; Neoplasms; Recombinant Proteins; Risk; Thrombophilia; Thrombosis; Venous Thromboembolism

Randomized clinical studies, carried out in patients with haematological malignancies and with solid tumours, have consistently demonstrated that treatment with recombinant human erythropoietin (Epo) increases haemoglobin levels, reduces blood transfusion requirements, and improves the quality of life. In addition, identification of erythropoietin receptor (EpoR) expression on many types of non-erythroid and cancer cells has spurred an interest in the extra-haematological activities of Epo itself and other erythropoiesis-stimulating agents (ESAs). Epo and its derivatives have emerged as major tissue-protective cytokines in ischaemic and degenerative damage of cardiovascular, neurological and renal diseases, while their angiogenetic and immunomodulatory properties indicate that their therapeutic potential may extend well beyond erythropoiesis alone. Both preclinical and clinical data, however, have suggested that they may contribute to tumour progression and prejudice survival when administered to anaemic cancer patients, though the results are equivocal and the assumed mechanisms by which tumour growth could be promoted are not fully understood. While these findings offer new perspectives, they nonetheless demand caution in the employment of ESAs. Further, well-designed experimental and clinical studies are warranted.

Topics: Anemia; Antineoplastic Agents; Blood Physiological Phenomena; Erythropoietin; Hematinics; Humans; Neoplasms; Receptors, Erythropoietin; Recombinant Proteins

Topics: Anemia, Hypochromic; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Small Cell; Clinical Protocols; Darbepoetin alfa; Data Interpretation, Statistical; Erythropoietin; Female; Filgrastim; Follow-Up Studies; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Granulocytes; Hematinics; Hematologic Neoplasms; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulins, Intravenous; Lung Neoplasms; Lymphoma; Lymphoma, Non-Hodgkin; Male; Multicenter Studies as Topic; Neoplasms; Neutropenia; Platelet Aggregation Inhibitors; Polycythemia Vera; Polyethylene Glycols; Randomized Controlled Trials as Topic; Recombinant Proteins; Research Design; Survival Analysis; Thrombocythemia, Essential; Treatment Outcome

Erythropoiesis-stimulating agents reduce anaemia in patients with cancer and could improve their quality of life, but these drugs might increase mortality. We therefore did a meta-analysis of randomised controlled trials in which these drugs plus red blood cell transfusions were compared with transfusion alone for prophylaxis or treatment of anaemia in patients with cancer.. Data for patients treated with epoetin alfa, epoetin beta, or darbepoetin alfa were obtained and analysed by independent statisticians using fixed-effects and random-effects meta-analysis. Analyses were by intention to treat. Primary endpoints were mortality during the active study period and overall survival during the longest available follow-up, irrespective of anticancer treatment, and in patients given chemotherapy. Tests for interactions were used to identify differences in effects of erythropoiesis-stimulating agents on mortality across prespecified subgroups.. Data from a total of 13 933 patients with cancer in 53 trials were analysed. 1530 patients died during the active study period and 4993 overall. Erythropoiesis-stimulating agents increased mortality during the active study period (combined hazard ratio [cHR] 1.17, 95% CI 1.06-1.30) and worsened overall survival (1.06, 1.00-1.12), with little heterogeneity between trials (I(2) 0%, p=0.87 for mortality during the active study period, and I(2) 7.1%, p=0.33 for overall survival). 10 441 patients on chemotherapy were enrolled in 38 trials. The cHR for mortality during the active study period was 1.10 (0.98-1.24), and 1.04 (0.97-1.11) for overall survival. There was little evidence for a difference between trials of patients given different anticancer treatments (p for interaction=0.42).. Treatment with erythropoiesis-stimulating agents in patients with cancer increased mortality during active study periods and worsened overall survival. The increased risk of death associated with treatment with these drugs should be balanced against their benefits.. German Federal Ministry of Education and Research, Medical Faculty of University of Cologne, and Oncosuisse (Switzerland).

Topics: Adolescent; Adult; Aged; Anemia; Antineoplastic Agents; Effect Modifier, Epidemiologic; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Humans; Linear Models; Male; Middle Aged; Neoplasms; Proportional Hazards Models; Randomized Controlled Trials as Topic; Recombinant Proteins; Research Design; Survival Rate; Treatment Outcome; Young Adult

Though elderly patients represent a majority of cancer patients, their treatment of is still inadequate, mainly due to the lack of data deriving from randomized clinical trials. Factors limiting the use of standard chemotherapy regimens in elderly cancer patients are the fear of toxicity and unexpected side effects. The assessment of comorbidity and the multidimensional geriatric assessment are of major importance in the decision plan. All supportive measures must be adopted in order to successfully treat vulnerable and unfit elderly patients with cancer, and in particular, the use of growth factors when chemotherapy is given with curative intent; rule out anemia and possible causes of anemia, and correct them whenever possible; choose cytotoxics according to expected adverse events and possible interference with concomitant medications. Particular attention must be paid to treatment of pain in the elderly with cancer. Caregivers must be involved in the treatment plan, and phone contacts with the patient and caregivers are needed to verify physical conditions and compliance to prescriptions.

Topics: Aged; Aging; Anemia; Antineoplastic Agents; Caregivers; Erythropoietin; Granulocyte Colony-Stimulating Factor; Humans; Neoplasms; Pain, Intractable

Regenerative Medicine, a recent new medical domain, aims to develop new therapies through the stimulation of natural regenerative processes also in human beings. In this field, Erythropoietin (EPO) represents a significant subject of research. Several studies allow the assertion that EPO, in different concentrations, has protective effects mainly on the central nervous system, cardiovascular system and renal tissue. This action is carried out through one of few regenerative activities of human beings: angiogenesis. This mechanism, which involves endothelial stem cells and VEGF (Vascular Endothelial Growth Factor), has been experimentally demonstrated with Recombinant human erythropoietin (rHuEPO) and Darbepoetin, a long-acting EPO derivate. Furthermore, the demonstration of a cardiac production of EPO in Fugu rubripes and in Zebrafish has led cardiologists to "discover" Erythropoietin, postulating a hypothetical role in treatment of cardiovascular disease for this hormone. This is some of the experimental evidence which demonstrates that EPO can be in reason considered an important element of research of Regenerative Medicine and put in the network of drugs able to regenerate tissues and organs.

Topics: Animals; Erythropoietin; Fishes; Humans; Models, Biological; Neoplasms; Neovascularization, Pathologic; Neovascularization, Physiologic; Regeneration; Regenerative Medicine

Erythropoiesis-stimulating agents (ESAs) reduce anemia in cancer patients and may improve quality of life, but there are concerns that ESAs might increase mortality.. Our objectives were to examine the effect of ESAs and identify factors that modify the effects of ESAs on overall survival, progression free survival, thromboembolic and cardiovascular events as well as need for transfusions and other important safety and efficacy outcomes in cancer patients.. We searched the Cochrane Library, Medline, Embase and conference proceedings for eligible trials. Manufacturers of ESAs were contacted to identify additional trials.. We included randomized controlled trials comparing epoetin or darbepoetin plus red blood cell transfusions (as necessary) versus red blood cell transfusions (as necessary) alone, to prevent or treat anemia in adult or pediatric cancer patients with or without concurrent antineoplastic therapy.. We performed a meta-analysis of randomized controlled trials comparing epoetin alpha, epoetin beta or darbepoetin alpha plus red blood cell transfusions versus transfusion alone, for prophylaxis or therapy of anemia while or after receiving anti-cancer treatment. Patient-level data were obtained and analyzed by independent statisticians at two academic departments, using fixed-effects and random-effects meta-analysis. Analyses were according to the intention-to-treat principle. Primary endpoints were on study mortality and overall survival during the longest available follow-up, regardless of anticancer treatment, and in patients receiving chemotherapy. Tests for interactions were used to identify differences in effects of ESAs on mortality across pre-specified subgroups. The present review reports only the results for the primary endpoint.. A total of 13933 cancer patients from 53 trials were analyzed, 1530 patients died on-study and 4993 overall. ESAs increased on study mortality (combined hazard ratio [cHR] 1.17; 95% CI 1.06-1.30) and worsened overall survival (cHR 1.06; 95% CI 1.00-1.12), with little heterogeneity between trials (I(2) 0%, p=0.87 and I(2) 7.1%, p=0.33, respectively). Thirty-eight trials enrolled 10441 patients receiving chemotherapy. The cHR for on study mortality was 1.10 (95% CI 0.98-1.24) and 1.04; 95% CI 0.97-1.11) for overall survival. There was little evidence for a difference between trials of patients receiving different cancer treatments (P for interaction=0.42).. ESA treatment in cancer patients increased on study mortality and worsened overall survival. For patients undergoing chemotherapy the increase was less pronounced, but an adverse effect could not be excluded.

Topics: Adult; Anemia; Child; Darbepoetin alfa; Disease-Free Survival; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Humans; Male; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins

Oxidative stress significantly impacts multiple cellular pathways that can lead to the initiation and progression of varied disorders throughout the body. It therefore becomes imperative to elucidate the components and function of novel therapeutic strategies against oxidative stress to further clinical diagnosis and care. In particular, both the growth factor and cytokine erythropoietin (EPO), and members of the mammalian forkhead transcription factors of the O class (FoxOs), may offer the greatest promise for new treatment regimens, since these agents and the cellular pathways they oversee cover a range of critical functions that directly influence progenitor cell development, cell survival and degeneration, metabolism, immune function, and cancer cell invasion. Furthermore, both EPO and FoxOs function not only as therapeutic targets, but also as biomarkers of disease onset and progression, since their cellular pathways are closely linked and overlap with several unique signal transduction pathways. Yet, EPO and FoxOs may sometimes have unexpected and undesirable effects that can raise caution for these agents and warrant further investigations. Here we present the exciting as well as the complex role that EPO and FoxOs possess to uncover the benefits as well as the risks of these agents for cell biology and clinical care in processes that range from stem cell development to uncontrolled cellular proliferation.

Topics: Animals; Biomarkers; Cell Survival; Diabetes Mellitus; Erythropoietin; Forkhead Transcription Factors; Humans; Neoplasms; Oxidative Stress; Receptors, Erythropoietin

The data and the conclusions of the Cochrane review of drug therapy for the management of cancer related fatigue (CRF) is analysed and summarized in this report. Overall, data is weakened substantially by a high degree of heterogeneity that stems primarily from the fact that fatigue is a subjective and multidimensional phenomenon Apart from erythropoietin and to some degree methylphenidate, there is no evidence that pharmacologic intervention may reduce CRF. CRF has major impact on quality of life for most patients suffering from a cancer disease. It is therefore of obvious importance to increase the focus on CRF - both in the pharmaceutical industry and in the professional-medical environment.

Topics: Antidepressive Agents, Second-Generation; Central Nervous System Stimulants; Erythropoietin; Evidence-Based Medicine; Fatigue; Hematinics; Humans; Methylphenidate; Neoplasms; Paroxetine; Progestins; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Epoetin-beta is used to treat patients with cancer undergoing chemotherapy to alleviate the symptoms of anaemia, reduce the risk of blood transfusions and improve quality of life (QoL).. This meta-analysis of all 12 randomised, controlled studies of epoetin-beta evaluated the impact of therapy at different Hb-initiation levels and to different target Hb levels on overall survival, tumour progression and thromboembolic events (TEE). An analysis of risk factors pre-disposing patients to TEEs under epoetin-beta therapy was also performed. A total of 2297 patients are included in the analysis.. Analyses based on various Hb-initiation levels indicate no detrimental impact on survival (HR 0.99; 95% CI 0.70, 1.40) and a favourable impact on disease progression (HR 0.73; 95% CI 0.57, 0.94) when epoetin-beta was used within its licensed indication (Hb initiation < or = 10 g dl(-1)) or the EORTC recommended level of 11 g dl(-1). An increased risk of TEEs is seen for all Hb-initiation level strata and a detrimental impact on survival is seen when initiating epoetin-beta therapy at Hb levels >11 g dl(-1). We observe no association between high target Hb levels (> or = 13 g dl(-1)) and an increased risk of mortality, disease progression or TEEs with epoetin-beta compared with control.. The results of this analysis indicate that epoetin-beta therapy has no detrimental impact on survival or tumour progression when initiated at Hb levels up to 11 g dl(-1). Furthermore, there is no evidence to suggest that high Hb values achieved during epoetin-beta therapy are associated with an increased mortality, disease progression or TEE rate.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Disease Progression; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Factors; Thromboembolism

Anemia of cancer and chronic inflammatory diseases is a frequent complication affecting quality of life. For cancer patients it represents a particularly bad prognostic. Low level of erythropoietin is considered as one of the causes of anemia in these pathologies. The deficiency in erythropoietin production results from pro-inflammatory cytokines effect. However, few data is available concerning molecular mechanisms involved in cytokine-mediated anemia. Some recent publications have demonstrated the direct effect of pro-inflammatory cytokines on cell differentiation towards erythroid pathway, without erythropoietin defect. This suggested that pro-inflammatory cytokine-mediated signaling pathways affect erythropoietin activity. They could interfere with erythropoietin-mediated signaling pathways, inducing early apoptosis and perturbing the expression and regulation of specific transcription factors involved in the control of erythroid differentiation. In this review we summarize the effect of tumor necrosis factor (TNF)alpha, TNF-related apoptosis-inducing ligand (TRAIL), and interferon (IFN)-gamma on erythropoiesis with a particular interest for molecular feature.

Topics: Anemia; Apoptosis; Cytokines; Erythropoiesis; Erythropoietin; Humans; In Vitro Techniques; Inflammation; Inflammation Mediators; Interferon-gamma; Models, Biological; Neoplasms; Oxidative Stress; Signal Transduction; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor-alpha

Epoetin beta effectively increases hemoglobin levels, reduces the need for transfusions and improves the quality of life in patients with symptomatic chemotherapy-induced anemia with a range of solid tumors and lymphoid malignancies. Recent evidence-based guidelines recommend the once weekly administration of epoetin beta. This once-weekly regimen is generally well tolerated, and studies to date have reported that epoetin beta has a neutral effect on survival of patients with cancer. The once-weekly administration regimen is convenient for the physician and patient alike. Methods to further optimize this treatment are discussed.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Erythropoietin; Evidence-Based Medicine; Hematinics; Hemoglobins; Humans; Neoplasms; Practice Guidelines as Topic; Quality of Life; Recombinant Proteins; Survival Rate

Epoetin-beta is used to treat patients with metastatic cancer undergoing chemotherapy to alleviate the symptoms of anaemia, reduce the risk of blood transfusions and improve quality of life. This meta-analysis of 12 randomised, controlled studies evaluated the impact of epoetin-beta on overall survival, tumour progression and thromboembolic events (TEEs). A total of 2297 patients were included in the analysis (epoetin-beta, n=1244; control, n=1053; 65% solid and 35% nonmyeloid haematological malignancies). A prespecified subgroup analysis assessed the effects in patients with a baseline Hb

Topics: Adult; Aged; Aged, 80 and over; Anemia; Disease Progression; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Analysis; Thromboembolism

Erythropoietin (EPO) has firstly known to regulate cell proliferation and differentiation along the erythroid lineage. Recent studies have shown that EPO, a pleiotropic cytokine, is proangiogenic and exerts broad tissue-protective effects in diverse nonhematopoietic organs. A series of studies have documented the expression of EPO and EPO receptor (EPO-R) in various cancer cells. The presence of an autocrine-paracrine EPO/EPO-R system may associate with the potential for stimulation of tumor neoangiogenesis and tumor proliferation, inhibition of apoptosis, or modulation of sensitivity to chemoradiotherapy. The complex mechanism needs further research. Recombinant human erythropoietin (rh-EPO) has been widely used in clinic to treat malignancy-associated anemia. Clinical trials have documented the efficacy of rh-EPO in increasing hemoglobin levels, reducing red blood cell (RBC) transfusion requirements and improving quality of life in cancer patients. However, three randomized trials reported negative outcomes with rh-EPO, as patients in the rh-EPO arm fared worse than their placebo-treated counterparts with progression-free survival. This review described EPO and EPO-R biology, focusing on the expression, pleiotropic function and mechanism on nonhematopoietic tissues especially on cancer cells.

Topics: Anemia; Erythropoietin; Humans; Neoplasms; Receptors, Erythropoietin; Recombinant Proteins

Patients who have cancer, particularly those undergoing chemotherapy, frequently become anemic. Therapy with erythropoiesis-stimulating agents (ESAs) is associated with an increase in hemoglobin levels, a reduction in transfusion requirements, and, according to many clinical trialists and experienced clinicians, an improvement in functional status, productivity, and quality of life. Several randomized trials of ESAs in patients who have cancer have recently reported inferior outcomes in tumor progression or survival, raising appropriate concerns about the safety of ESAs in oncology. However, 3 important caveats to these reports exist. First, these clinical trials did not reflect the common use of ESAs in oncology practice (i.e., to treat, rather than prevent, anemia in patients undergoing chemotherapy). Second, the trials were seriously flawed and did not meet reasonable standards for cancer progression or survival trials. Third, during the same period, randomized trials were presented or published that showed no negative impact on tumor progression or survival; these trials have approximately the same shortcomings as trials that suggest a safety issue exists. The lack of definitive answers about the safety of ESAs for treating chemotherapy-related anemia has placed physicians, regulators, and most importantly patients in a difficult position that can only be addressed with additional data. This article reviews relevant preclinical and clinical available data to help improve understanding and guide decision making.

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

Anemia is the most frequent hematologic abnormality among cancer patients. Its pathophysiology comprises reduction in erythrocyte half-life, poor iron reutilization by the bone marrow, and inadequate response to erythropoietin (EPO), with reduced endogenous EPO (eEPO) levels. Current treatment implies the use of erythropoiesis- stimulating agents (ESA), to which 35-48% of patients show primary resistance. The search for predictors of response to ESA treatment has been inconclusive. Iron or vitamin deficiency, the recent need for transfusion, or a lack of hemoglobin increase within the first 2-4 weeks usually predict resistance to ESA. High serum eEPO levels at treatment initiation (>100-150 mU/ml) may also predict resistance, especially in hematologic malignancies, but the results in solid tumors are not consistent. Although patients with cancer-related anemia show higher eEPO levels than patients without anemia, there is extreme variability among individuals. Future studies are needed to clarify eEPO usefulness in predicting response to ESA treatment.

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematinics; Humans; Neoplasms; Predictive Value of Tests; Recombinant Proteins

Cancer-related fatigue is an important clinical problem. It is common, distressing, and often difficult to treat. There is a role for drug treatment of cancer-related fatigue, but no consensus has been reached on which drugs are useful. This systematic review and meta-analysis aims to review the available evidence and make recommendations for practice and research.. We searched the Cochrane register of controlled trials (through the second quarter 2007), Medline (January 1, 1966, through August 1, 2007), and EMBASE (January 1, 1980, through August 1, 2007) by use of a predetermined list of search terms. Cochrane Collaboration meta-analysis review methodology was used for this study. The change in fatigue score on the instrument used in each study and other outcomes of interest (adverse events and withdrawal rates) were compared between treatment and control arms by use of the standardized mean difference (SMD) with 95% confidence intervals (CIs). All statistical tests were two-sided.. We identified 27 eligible trials of drug treatments for cancer-related fatigue (with a total of 6746 participants). The overall effect size for all drug classes was small. A meta-analysis of two studies (n = 264 patients) indicated that methylphenidate (a psychostimulant) was superior to placebo (standardized mean difference [SMD] in change in fatigue score = -0.30, 95% confidence interval [CI] = -0.54 to -0.05; P = .02) for treating cancer-related fatigue. A meta-analysis of 10 studies (n = 2226 patients) evaluating erythropoietin in anemic cancer patients who were undergoing chemotherapy indicated that erythropoietin was superior to placebo (SMD = -0.30, 95% CI = -0.46 to -0.29; P = .008). Among anemic patients (four studies with n = 964 patients), improvement in fatigue was associated with darbepoetin treatment compared with placebo treatment (SMD = -0.13, 95% CI = -0.27 to 0.00; P = .05). Progestational steroids and paroxetine were no better than placebo in the treatment of cancer-related fatigue.. There is some evidence that treatment of cancer-related fatigue with methylphenidate appears to be effective. More robust evidence indicates that treatment with hematopoietic agents appears to relieve cancer-related fatigue caused by chemotherapy-induced anemia. Further confirmatory trials are required for both observations.

Topics: Anemia; Antidepressive Agents, Second-Generation; Antineoplastic Agents; Central Nervous System Stimulants; Darbepoetin alfa; Dopamine Uptake Inhibitors; Erythropoietin; Fatigue; Hematinics; Humans; Methylphenidate; Neoplasms; Odds Ratio; Paroxetine; Progestins; Randomized Controlled Trials as Topic; Treatment Outcome

Anemia with consequent tissue hypoxia is common problem in cancer patients. Developed via various patophysiological mechanisms, it has deleterious effect on quality of life and survival of patients with cancer. Recognition of symptoms and timely initiation of treatment improve patients' quality of life, as well as efficacy of oncological treatment. Red blood cells transfusions are well known and efficient way of anemia correction. They are "golden standard" in treatment of cancer-related anemia today, and are unavoidable in almost all patients with hemoglobin concentration below 80 g/L. Newest therapy guidelines in developed countries, supported by recent literature, encourage use of recombinant human erythropoietin (rHu-EPO), although detailed meta-analyses and prospective randomized clinical trials have shown that rHu-EPO decreases the need for transfusions in only 9-45% patients with cancer, only if they have mild anemia, rHu-EPO increases incidence of thromboembolic events, and suspicion arises that it supports tumor cells growth and multiplication. Therefore, it is necessary to define subgroups of patients which are best candidates for rHu-EPO therapy, to accomplish lower intensity of transfusion therapy.

Topics: Anemia; Animals; Blood Transfusion; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Erythropoietin (Epo) has a long-lasting history as the hormon that allows production of red blood cells. It is now well established that, besides erythropoiesis, Epo has the ability to sustain proliferation of myeloid lineages. More recently, extra-haematological roles have been described for Epo. Its receptor, EpoR, has been detected at the membrane of several neoplastic and normal cell types from the central nervous system and other non haematological cell lines. Whereas Epo-EpoR have been detected several years ago in some extra-haematological normal lineages, their role has long been underestimated whereas they may be crucial for proliferation and survival. Consequently, efforts have recently increased to identify the precise role of Epo-EpoR in a variety of cell types. This allowed identification of physiologically relevant targets that led to original therapeutic strategies.

Topics: Animals; Central Nervous System; Erythropoietin; Humans; Kidney; Neoplasms; Receptors, Erythropoietin; Recombinant Proteins

Erythropoietin (EPO) has long been recognized as the major hematopoietic cytokine regulating normal erythropoiesis. Moreover, there is a growing interest in the non-erythropoietic, tissue-protective effects of EPO. Because of its potential to correct anemia, EPO has been increasingly prescribed to cancer patients. However, although recombinant human Epo (rHuEPO) significantly reduces the risk for red blood cell transfusions in cancer patients, recent clinical studies have reported decreased survival and disease control following rHuEPO treatment in patients with different cancer types. The issue of EPOR expression in tumor cells is critical in this respect. The expression of EPOR in tumor cells raises the possibility that exogenous rHuEPO may directly influence tumor growth or sensitivity to chemo-radiation therapy. In addition, EPOR expression in endothelial cells suggests what potential effects EPO may have on tumor capillaries, such as the stimulation of angiogenesis. However, as experimental studies reveal, the overall direct effect of EPO-EPOR signaling on cancer progression and therapy is not a straightforward one. The current paper provides an update on the biology of EPO, and discusses its utility in the treatment of cancer patients.

Topics: Erythropoietin; Hematopoietic System; Humans; Hypoxia; Models, Theoretical; Neoplasms; Recombinant Proteins; Signal Transduction; Survival Rate

Signalling in multicellular organisms is mediated by complex networks that integrate extracellular and intracellular signals to generate appropriate responses regulating cell proliferation, differentiation and survival. Downstream of many cytokine and growth hormone receptors, receptor-associated JAKs (Janus kinases) activate transcription factors of the STAT (signal transducer and activator of transcription) protein family and thereby mediate signal transduction from the plasma membrane to the nucleus. The JAK/STAT pathway has been shown to be constitutively activated in a wide array of human malignancies. To elucidate mechanisms contributing to tumour formation and identify system properties of the JAK/STAT signalling pathway, a systems biology approach can be employed. So far the majority of studies available have focused on down-regulation of the signalling pathway based on simulations. However, a data-based model of the core module of the JAK2/STAT5 signalling pathway showed that rapid nucleocytoplasmic cycling of STAT5 is an essential pathway property. In the future, combining assays for quantitative analysis at different levels will be important to gain deeper insight into molecular mechanisms regulating intracellular communication mediated by such complex dynamic systems as signalling pathways and their targets.

Topics: Animals; Cell Nucleus; Erythropoietin; Humans; Janus Kinases; Neoplasms; STAT Transcription Factors; Systems Biology

Erythropoiesis-stimulating agents reduce the transfusion requirements of anemic cancer patients receiving chemotherapy. Risks associated with the use of erythropoiesis-stimulating agents in cancer patients have more recently been identified.. Several recently published phase III trials and a meta-analysis have shown an increased risk of venous thromboembolism and a decreased survival in anemic cancer patients treated with erythropoiesis-stimulating agents.. To minimize risks associated with erythropoiesis-stimulating agent use in cancer patients, the most recent American Society of Clinical Oncology/American Society of Hematology clinical practice guidelines and Food and Drug Administration recommendations should be followed.

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Clinical Trials as Topic; Erythropoietin; Humans; Iron; Neoplasms; Quality of Life; Risk; Signal Transduction; Treatment Outcome; United States; United States Food and Drug Administration; Venous Thromboembolism

Anaemia is the most common haematological abnormality in cancer patients, and unfortunately, it is often under-recognised and undertreated. The aetiopathology of anaemia in cancer patients is complex and is usually multifactorial. There is enough evidence suggesting that tumour hypoxia in anaemic patients has a negative impact on the treatment outcomes in cancer patients. The use of recombinant human erythropoietin is becoming a new standard of care in cancer patients. Various well-controlled studies have shown that the use of erythropoietin (EPO) increases the haemoglobin level, thereby decreasing the need for frequent transfusions and improving the tumour responses, cancer-free survival and quality-of-life parameters in cancer patients. However, a few recent clinical trials failed to replicate the survival benefit. Hence, a free unrestricted use of EPO is to be avoided. The past belief that anaemia does not matter in cancer patients is now considered invalid and is being seriously challenged. This article aims to present some recent findings on the impact of anaemia on outcomes, with discussion on the possible causes and effects. The benefits of the use of EPO analogues in cancer-related anaemia are also presented.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Disease-Free Survival; Erythropoietin; Hemoglobins; Humans; Hypoxia; Neoplasms; Quality of Life; Recombinant Proteins; Treatment Outcome

To update the American Society of Clinical Oncology/American Society of Hematology (ASCO/ASH) recommendations for the use of epoetin. The guideline was expanded to address use of darbepoetin and thromboembolic risk associated with these agents.. An Update Committee ("Committee") reviewed and analyzed data published since 2002 through July 2007. MEDLINE and the Cochrane Collaboration Library databases were searched.. For patients with chemotherapy-associated anemia, the Committee continues to recommend initiating an erythropoiesis-stimulating agent (ESA) as hemoglobin (Hb) approaches, or falls below, 10 g/dL, to increase Hb and decrease transfusions. ESA treatment continues to be recommended for patients with low-risk myelodysplasia for similar reasons. There is no evidence showing increased survival as a result of ESA treatment. Conclusive evidence is lacking that, absent clinical circumstances necessitating earlier treatment, initiating ESAs at Hb levels greater than 10 g/dL either spares more patients from transfusion or substantially improves their quality of life. Starting doses and dose modifications based on response or lack thereof should follow the package insert. Continuing ESAs beyond 6 to 8 weeks in the absence of response, assuming appropriate dose increase has been attempted in nonresponders as per US Food and Drug Administration-approved label, does not seem to be beneficial, and ESA therapy should be discontinued. The Committee recommends monitoring iron stores and supplementing iron intake for ESA-treated patients. ESAs should be used cautiously with chemotherapy, or in clinical states, associated with elevated risk for thromo-embolic complications. The Committee also cautions against ESA use for patients with cancer who are not receiving chemotherapy, since recent trials report increased thromboembolic risks and decreased survival under these circumstances.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Hematology; Humans; Medical Oncology; Neoplasms; Recombinant Proteins; Societies, Medical

Anemia in children with cancer is not an uncommon complication and is usually multifactorial in etiology. In numerous trials in adult cancer patients, treatment with recombinant erythropoietin has been shown to increase hemoglobin levels, reduce red blood cell transfusion requirements, and improve quality of life. Much less has been published of its use in the prevention or treatment of cancer-associated anemia (CAA) in children, in whom chemotherapy is usually more intensive and likely to result in greater myelosuppression. This review critically evaluates the published evidence of its use in childhood cancer especially; its safety and efficacy in the prevention and treatment of CAA and some indications for its use in childhood cancer are suggested.

Topics: Age Factors; Anemia; Child; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

The erythropoiesis-stimulating agents (ESAs) erythropoietin and darbepoetin are licensed to treat chemotherapy-associated anemia in patients with nonmyeloid malignancies. Although systematic overviews of trials have identified venous thromboembolism (VTE) risks, none have identified mortality risks with ESAs.. To evaluate VTE and mortality rates associated with ESA administration for the treatment of anemia among patients with cancer.. A published overview from the Cochrane Collaboration (search dates: January 1, 1985-April 1, 2005) and MEDLINE and EMBASE databases (key words: clinical trial, erythropoietin, darbepoetin, and oncology), the public Web site of the US Food and Drug Administration and ESA manufacturers, and safety advisories (search dates: April 1, 2005-January 17, 2008).. Phase 3 trials comparing ESAs with placebo or standard of care for the treatment of anemia among patients with cancer.. Mortality rates, VTE rates, and 95% confidence intervals (CIs) were extracted by 3 reviewers from 51 clinical trials with 13 611 patients that included survival information and 38 clinical trials with 8172 patients that included information on VTE.. Patients with cancer who received ESAs had increased VTE risks (334 VTE events among 4610 patients treated with ESA vs 173 VTE events among 3562 control patients; 7.5% vs 4.9%; relative risk, 1.57; 95% CI, 1.31-1.87) and increased mortality risks (hazard ratio, 1.10; 95% CI, 1.01-1.20).. Erythropoiesis-stimulating agent administration to patients with cancer is associated with increased risks of VTE and mortality. Our findings, in conjunction with basic science studies on erythropoietin and erythropoietin receptors in solid cancers, raise concern about the safety of ESA administration to patients with cancer.

Topics: Anemia; Clinical Trials, Phase III as Topic; Darbepoetin alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Risk; Survival Rate; Venous Thromboembolism

For cancer treatment-related anemia, it is recommended to use erythropoietin or darbepoetin alpha by the National Comprehensive Cancer Network (NCCN). The guideline proposed the risk assessment for anemia, as well. The introduction of erythropoietin or darbepoetin alpha for anemia in treated cancer patients is based on the improvement of quality of life. For patients with myelodysplastic syndrome (MDS), those with 5q- anomaly is recommended to use lenalidomide and low-risk MDS patients without 5q- and serum erythropoietin of less than 500 mU/ml are recommended to treat with erythropoietin or darbepoetin alpha. These new agents are currently under clinical trials in Japan.

Topics: Anemia; Benzoates; Clinical Trials as Topic; Darbepoetin alfa; Deferasirox; Erythropoietin; Hematinics; Humans; Iron Chelating Agents; Iron Overload; Lenalidomide; Myelodysplastic Syndromes; Neoplasms; Thalidomide; Triazoles

Anemia is common in patients with cancer. The incidence and severity of anemia depend on the type and extent of the malignancy. Anemia may be the result of the malignancy itself, cancer treatment, blood losses, hemolysis or inflammatory cytokines associated with chronic disease. Anemia can have a profound impact on physical and psychosocial function and quality of life. However, in Japan, only iron supplementation and blood transfusion were available for the treatment of anemia with cancer. On the other hand, in Europe and America, erythropoietic agents such as erythropoietin and novel erythropoiesis stimulating protein (NESP) have been clinically used for anemia in patients with cancer.

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Hematinics; Hemolysis; Hemorrhage; Humans; Iron Metabolism Disorders; Neoplasms; Prognosis; Recombinant Proteins

Several studies with erythropoiesis-stimulating agents (ESAs) have raised a number of safety issues. Therefore, a discussion of available data in light of the current EORTC guidelines 2006 on the use of ESAs in anemic patients is warranted.. Literature is reviewed with respect to experimental and clinical data on the effect of ESA therapy on tumor growth both in the preclinical setting and on patient survival.. Studies showing an adverse effect of ESA therapy on patient survival generally exhibit considerable methodological deficiencies. Moreover, they investigated treatment situations for which ESAs are not approved and/or did not involve recommended baseline ("intervention") or target hemoglobin levels.. When used as indicated, ESAs are valuable and safe drugs for the treatment of anemia and do not negatively affect patient survival. In particular, the data situation confirms the importance and correctness of the EORTC guidelines 2006 and their recently updated version. It is therefore recommended that these guidelines continue to be strictly followed in the treatment of chemotherapy-induced anemia.

Topics: Adult; Anemia; Animals; Antineoplastic Agents; Blood Transfusion; Clinical Trials as Topic; Clinical Trials, Phase II as Topic; Disease Models, Animal; Disease Progression; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Meta-Analysis as Topic; Mice; Neoplasms; Neoplasms, Experimental; Oxygen; Practice Guidelines as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Rats; Receptors, Erythropoietin; Recombinant Proteins; Risk Factors; Safety; Tumor Cells, Cultured

Certain studies in which erythropoiesis-stimulating agents (ESAs) have been given not with the aim of correcting anemia but to achieve higher target levels of hemoglobin have shown significantly poorer survival among treated patients. However, studies in which ESAs were administered with the aim of reducing the need for RBC transfusions in patients with chemotherapy-associated anemia demonstrate that the use of these agents is not associated with any adverse effect on survival when compared with placebo controls. We can therefore be reassured that using ESAs within the labeled indications will not adversely affect patient outcome.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Drug Approval; Erythropoietin; Hematinics; Hemoglobins; Humans; Meta-Analysis as Topic; Neoplasms; Recombinant Proteins

Venous thromboembolic events (VTEs) are frequent in cancer patients because of the effects of malignant disease, its treatment, and comorbidities. The higher risk for VTEs associated with the use of erythropoiesis-stimulating agents (ESAs) appears to be a class effect but may be particularly pronounced when these agents are used in patients who are not anemic at baseline and/or to achieve hemoglobin targets higher than those recommended in current labeling. Particular attention should be taken to assess the balance of risks and benefits in patients with a history of thromboembolism. If the goal of treatment of patients with chemotherapy-associated anemia is aimed to raise the hemoglobin level to 12 g/dl, and is confined to that, ESA-induced VTEs should rarely be a problem.

Topics: Anemia; Antineoplastic Agents; Drug Labeling; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Recombinant Proteins; Thromboembolism

Given the apparent presence of erythropoietin receptors (EPORs) in cancer tissues, questions have been raised about the possible influence of erythropoiesis-stimulating agents (ESAs) on tumor growth and proliferation. Preclinical studies of ESAs have shown no greater tumor proliferation in cell lines and no adverse effect on treatment outcomes in animal models. Furthermore, it appears that the commercially available antibodies that have been used in clinical studies are not specific to EPORs. In particular, they detect isoforms of heat shock protein 70, which is found in tumor cells and is associated with poor prognosis. For this reason, results from clinical studies purporting to relate the administration of ESAs to shorter survival must be considered inconclusive and complicated by methodological and sampling issues. Ongoing studies will help clarify whether the existence of the EPOR has any relevance at all in the cancer setting.

Topics: Animals; Antibodies, Monoclonal; Antibody Specificity; Erythropoietin; HSP70 Heat-Shock Proteins; Humans; Immunohistochemistry; Neoplasms; Receptors, Erythropoietin; Recombinant Proteins; Tumor Cells, Cultured

Tumor hypoxia, mostly resulting from poor perfusion and anemia, is one of the key factors in inducing the development of cell clones with an aggressive and treatment-resistant phenotype that leads to rapid progression and poor prognosis. Studies in patients with solid tumors suggest that there is a range of hemoglobin (Hb) concentrations that is optimum for tumor oxygenation. When used to achieve an Hb level within this range, erythropoiesis-stimulating agents (ESAs) can be expected to increase tumor oxygenation, and this may favorably influence sensitivity to treatment as well as quality of life. There is no robust evidence that ESAs, when used as indicated, have a negative effect on survival in patients with solid tumors. When used outside the indications recommended, the rise in Hb level that results may reduce tumor blood flow and tissue oxygenation because of a raised viscosity within the abnormal tumor microvasculature. In the current situation, it remains important to use ESAs within the approved indications and according to treatment guidelines such as those developed by the European Organization for Research and Treatment of Cancer.

Topics: Anemia; Cell Differentiation; Cell Hypoxia; Cell Proliferation; Cell Transformation, Neoplastic; Erythropoietin; Hematinics; Hemoglobins; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Neoplasms; Oxygen; Recombinant Proteins

Erythropoiesis-stimulating agents are indicated for the treatment of chemotherapy induced-anemia in cancer patients. Controlled clinical studies have shown that epoetin alfa consistently and significantly increases levels of hemoglobin (Hb), decreases the need for RBC transfusion, and improves the quality of life that is of such importance in cancer patients with a limited life expectancy. The rise achieved in Hb level correlates with an improvement in quality of life. Studies have also demonstrated that earlier initiation of epoetin therapy (i.e., starting treatment at an Hb level of 10-11 g/dl rather than waiting for Hb to fall to <10 g/dl) is associated with a faster achievement of an optimal Hb level, a lower transfusion requirement, and a maintained quality of life.

Topics: Anemia; Antineoplastic Agents; Erythrocyte Transfusion; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Recombinant Proteins

Beginning 1998, a working group of specialists convened by the guidelines department (Standards, Options and Recommendations: SOR) of the National French Federation of Comprehensive Cancer Centres (FNCLCC) published then regularly updated Recommendations relative to the use of ESA in anaemic patients with cancer. This article presents a short version of the Recommendations updated in 2007.. This updating process is based on the methodology developed and used in the "Standards, Options: Recommendations" programme. The methodological approach combines systematic review with the judgement of a multidisciplinary group of experts. A Recommendation is a proposal of one or several clinical attitudes intended to improve cancer patient care. There are two levels of gradation for the Recommendations: Standards and Options. Their setting takes into account the organisational context of care, the particular situation of the patient and the expression of his preferences. Before publication, the RPC-SOR are re-examined by independent reviewers selected according to the same principles as the group of expert writers.. New data are sufficiently important to update the latest Recommendations validated in 2003. Thus, five clinical questions were updated. The resulting modifications were either major (new Options or new Standards) or minor (increased level of evidence). It should be noted that for the clinical question--use of ESA in radiotherapy--new data are not sufficient to generate modifications in the initial Recommendations which remain valid.. Because of the important new data published on the subject between 2003 and 2007, it appears relevant to re-examine these Recommendations according to a systematic monitoring process which should be renewed in 2 years.

Topics: Adult; Anemia; Child; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; France; Hematinics; Humans; Iron Compounds; Neoplasms; Recombinant Proteins

In vitro and animal model studies have shown erythropoietin receptor (Epo-R) mRNA and/or protein may be present in a range of human tumours and cancer cell lines, and erythropoiesis-stimulating agents (ESAs) have been reported to have tumour cell growth-modulating effects. Following a review of the literature, we conclude that considerations must be made when interpreting data from the preclinical studies. First, supraphysiological doses of ESAs were usually used. Second, there are no well validated, commercially available antibodies for identifying the presence and functionality of Epo-R at the protein level, either intracellularly or on the cell surface. Data from previous studies that used antibodies only for Epo-R detection must therefore be interpreted with caution. Together with diverging results in the literature, these methodological limitations indicate that findings from preclinical studies must not be over-translated in terms of their clinical relevance to patients with cancer.

Topics: Anemia; Cell Hypoxia; Disease Progression; Drug Evaluation; Erythropoiesis; Erythropoietin; Humans; Neoplasms; Neovascularization, Pathologic; Receptors, Erythropoietin

Cancer-related anaemia, which affects many patients with cancer, can effectively be treated by erythropoietic proteins. Erythropoietic proteins increase haemoglobin levels, reduce the risk for transfusions and also improve the quality of life of patients. When used according to published practice guidelines, these proteins benefit many patients and are generally well tolerated. Important side effects are hypertension and thromboembolic events, either of which occurs in < 10% of the patients. Administration only in anaemic patients, avoidance of target haemoglobin levels > 130 g/l, proper dose adjustments and close monitoring during treatment will ensure the clinical safety of these proteins. However, the association between erythropoietic proteins and outcome of anticancer therapy, including survival, requires further study.

Topics: Erythropoietin; Humans; Neoplasms; Recombinant Proteins; Survival Rate

Anaemia is frequently diagnosed in patients with cancer, and may have a detrimental effect on quality of life (QoL). We previously conducted a systematic literature review (1996-2003) to produce evidence-based guidelines on the use of erythropoietic proteins in anaemic patients with cancer.[Bokemeyer C, Aapro MS, Courdi A, et al. EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer. Eur J Cancer 2004;40:2201-2216.] We report here an update to these guidelines, including literature published through to November 2005. The results of this updated systematic literature review have enabled us to refine our guidelines based on the full body of data currently available. Level I evidence exists for a positive impact of erythropoietic proteins on haemoglobin (Hb) levels when administered to patients with chemotherapy-induced anaemia or anaemia of chronic disease, when used to prevent cancer anaemia, and in patients undergoing cancer surgery. The addition of further Level I studies confirms our recommendation that in cancer patients receiving chemotherapy and/or radiotherapy, treatment with erythropoietic proteins should be initiated at a Hb level of 9-11 g/dL based on anaemia-related symptoms rather than a fixed Hb concentration. Early intervention with erythropoietic proteins may be considered in asymptomatic anaemic patients with Hb levels 11.9 g/dL provided that individual factors like intensity and expected duration of chemotherapy are considered. Patients whose Hb level is below 9 g/dL should primarily be evaluated for need of transfusions potentially followed by the application of erythropoietic proteins. We do not recommend the prophylactic use of erythropoietic proteins to prevent anaemia in patients undergoing chemotherapy or radiotherapy who have normal Hb levels at the start of treatment, as the literature has not shown a benefit with this approach. The addition of further supporting studies confirms our recommendation that the target Hb concentration following treatment with erythropoietic proteins should be 12-13 g/dL. Once this level is achieved, maintenance doses should be titrated individually. There is Level I evidence that dosing of erythropoietic proteins less frequently than three times per week is efficacious when used to treat chemotherapy-induced anaemia or prevent cancer anaemia, with studies supporting the use of epoetin alfa and epoetin beta weekly and darbepoetin alfa given every week or every 3 weeks.

Topics: Anemia; Antineoplastic Agents; Bone Marrow Transplantation; Chronic Disease; Erythropoietin; Hematopoietic Stem Cell Transplantation; Humans; Hypertension; Iron; Neoplasms; Practice Guidelines as Topic; Radiotherapy; Thromboembolism

Anemia has an incidence both on the quality of life and the evolution of cancer. Anemia may result in cancer from either a bone marrow infiltration of cancer cells or a cytotoxic effect of chemotherapy and/or radiotherapy, or both. EPO is a glycoprotein which stimulates erythrocyte formation by bone marrow progenitory cells. Recombinant EPO has considerably improved treatment of anemic patients, by increasing hemoglobin serum levels and reducing the need for blood transfusion. The quality of life of cancer patients is thus improved and several studies highlight the beneficial role of EPO on the clinical outcome. A preclinical background and some clinical data suggest however a detrimental role of EPO in cancer by a possible stimulation of tumor growth. There is a need of more clinical trials in order to assess the effects of EPO on tumors and their treatment.

Topics: Anemia; Animals; Antineoplastic Agents; Clinical Trials as Topic; Erythropoietin; Hemoglobins; Humans; Neoplasms; Quality of Life; Radiotherapy; Risk Factors

The elements and limitations of pharmacoeconomic models, types of analytic methods used in pharmacoeconomic evaluations, outcomes used in studies of anemia treatments, and comparative efficacy and cost-effectiveness of the two available erythropoietic therapies in the treatment of anemia in cancer and critical care patients are discussed.. Clinical, humanistic, and economic outcomes should be taken into consideration in pharmacoeconomic models. The validity of such models may be compromised by a lack of outcome data, unreasonable assumptions, the heterogeneity of the patient population, patient selection bias in comparative studies, and inconsistent use of instruments to measure outcomes. The degree of anemia in patients with cancer correlates with health-related quality of life (QOL). Erythropoietic therapy increases hemoglobin concentrations and QOL, reduces the need for blood transfusions, and is cost-effective for treating anemia in cancer and critical care patients. Epoetin alfa may provide a more rapid hemoglobin response and improvement in QOL at a lower cost than darbepoetin alfa. Front loading with weekly doses of either erythropoietic agent followed by a three-week-long dosing interval for maintenance treatment may be used to quickly correct anemia, improve convenience, and reduce costs.. Erythropoietic therapy for the treatment of anemia in cancer and critical care patients is cost-effective.

Topics: Anemia; Cost-Benefit Analysis; Critical Care; Critical Illness; Darbepoetin alfa; Economics, Pharmaceutical; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Quality of Life; Recombinant Proteins

The incidence, etiology, impact, and considerations in developing guidelines for treating anemia in patients with cancer are described.. Anemia is common in patients with cancer. The incidence and severity of anemia depend on the type and extent of the malignancy; the type, schedule, and intensity of cancer therapy; and patient age, gender, and comorbid conditions. Anemia may be the result of the malignancy itself, cancer treatment, blood losses, nutritional deficiencies, hemolysis, endocrine disorders, or inflammatory cytokines associated with chronic disease. Anemia can have a profound impact on physical and psychosocial function and quality of life. Guidelines and protocols for treating anemia should be evidence-based and take into consideration patient age, the type and extent of malignancy, comorbid conditions, and the etiology and impact of anemia. Patient-specific issues that guidelines should address include strategies for identifying patients with anemia, treating anemia, evaluating the response to treatment, and modifying treatment based on response. Erythropoietic agents are preferred over blood transfusions for patients whose anemia is chronic, although transfusions are indicated for acute, severe blood losses. Iron supplementation often is required in patients receiving erythropoietic therapy or with iron deficiency due to hemorrhage.. The use of evidence-based guidelines and protocols that take into consideration the heterogeneity of patients with cancer can optimize anemia treatment.

Topics: Anemia; Blood Transfusion; Clinical Protocols; Comorbidity; Endocrine System Diseases; Erythropoietin; Humans; Incidence; Neoplasms; Practice Guidelines as Topic

Patients with cancer-related anaemia generally have a poor prognosis. Evidence suggests that an effective erythropoietic protein (epoetin)-mediated haemoglobin (Hb) response provides marked improvement in quality of life (QoL). An early Hb response to erythropoietic protein therapy in these patients would appear ideal but few studies have compared the speed of response to different erythropoietic proteins, or the potential benefits associated with an early Hb response.. The pharmacokinetic/pharmacodynamic profiles of commercially available erythropoietic proteins are reviewed along with available clinical data to examine Hb response and associated clinical outcomes for each of these agents. Randomised, head-to-head trials comparing epoetin alfa and darbepoetin alfa suggest that patients administered with epoetin alfa achieve a satisfactory Hb response significantly earlier than those given darbepoetin alfa, and with consistently lower monthly transfusion rates. Non-comparative studies support this, suggesting also that epoetin beta may provide a relatively faster Hb response in a greater number of patients than either epoetin alfa or darbepoetin alfa, irrespective of malignancy or chemotherapy type. Moreover, studies suggest consistently that a 'front-loading' dosing regimen with epoetin alfa does not convey improved speed of Hb response over epoetin beta administered according to current clinical practice guidelines.. Given the poor prognosis of anaemic patients with cancer, the use of an agent which provides clinical benefits quickly but with minimal thromboembolic risk, should be considered an essential component of anaemia management in these patients. However, more head-to-head studies are required to confirm the relative efficacy of currently available erythropoietic proteins.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Neoplasms; Quality-Adjusted Life Years; Recombinant Proteins; Retrospective Studies; Thromboembolism; Treatment Outcome

Healthcare organizations must evaluate the cost effectiveness of the alternative therapies that are available to treat anemia and improve quality of life (QoL) of patients with cancer, that is, erythropoietic protein therapy and blood transfusion.. Pharmacoeconomic studies that evaluated the cost of not treating anemia or treating with transfusion or erythropoietic protein therapy were reviewed and compared. Studies of individual erythropoietic proteins (epoetin alfa, epoetin beta or darbepoetin alfa) were also assessed. As no prospective trials have compared the erythropoietic proteins, retrospective studies and the results of separate trials were analyzed. The database searched for this review was PubMed (open date to August 2006). Recent conference abstracts were also searched (2003-July 2006).. There is a high cost associated with anemia in cancer patients. Treatment of anemia is likely to lead to increased hemoglobin (Hb) levels and improved QoL as principal outcomes. Therefore, in assessing erythropoietic protein versus transfusion, it is more appropriate to use Hb or QoL as endpoint rather than quality adjusted life year. Studies with the former approach showed that erythropoietic protein therapy is more cost effective than transfusion. Also, its cost effectiveness should be improved with the use of evidence-based guidelines for patient selection and more tailored utilization. Increasing evidence suggests there might be differences among the erythropoietic proteins in terms of response rate, speed of response, and need for dose escalation.. Significant costs are incurred when anemia in cancer is not treated. Erythropoietic protein therapy is more cost effective than blood transfusion for the treatment of cancer-related anemia. Transfusion should be reserved for patients with poor responses to erythropoietic protein or for the emergency setting, when rapid improvement in Hb is required.

Topics: Absenteeism; Anemia; Blood Transfusion; Budgets; Cost-Benefit Analysis; Darbepoetin alfa; Drug Costs; Epoetin Alfa; Erythropoietin; Health Care Costs; Hemoglobins; Humans; Iron; Neoplasms; Quality of Life; Quality-Adjusted Life Years; Recombinant Proteins; Treatment Outcome

Topics: Aged; Anemia; Cost of Illness; Erythropoietin; Evidence-Based Medicine; Geriatrics; Hematinics; Humans; Kidney Failure, Chronic; Neoplasms; Patient Selection; Quality of Life; Recombinant Proteins; Treatment Outcome

Anemia raises special concerns in older cancer patients. This review addresses the prevalence, causes, and mechanisms of anemia in older individuals, the complications of anemia in this population (including its impact on cancer treatment), and the appropriate management of anemia in the elderly.

Topics: Aged; Aging; Anemia; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms

Anemia is common in patients with cancer or myelodysplastic syndrome. Erythropoietic therapy offers an effective way to manage anemia by increasing hemoglobin levels, decreasing transfusion requirements, and alleviating symptoms. We reviewed data showing the feasibility and effectiveness of treatment with the erythropoiesis-stimulating protein darbepoetin alfa at extended dosing intervals to treat anemia in patients with cancer receiving multicycle chemotherapy. We also explored the darbepoetin alfa's potential for treating anemia in patients with myelodysplastic syndrome. Data from clinical studies and drug therapy evaluations confirm that darbepoetin alfa administered weekly, every 2 weeks, and every 3 weeks corrects and maintains hemoglobin levels in patients with chemotherapy-induced anemia. In addition, the data demonstrate that both weight-based and fixed dosing with darbepoetin alfa are effective, and that early intervention to treat anemia has clinical benefits. Darbepoetin alfa also is an effective treatment for anemia in patients with cancer not receiving chemotherapy, at extended dosing intervals of at least 3 weeks. Extended dosing for anemia treatment can provide benefits for patients, caregivers, and clinicians because it reduces the number of clinic visits needed and permits synchronizing anemia treatment with chemotherapy cycles. Data from recent studies suggest that darbepoetin alfa is effective for treating anemia in patients with myelodysplastic syndrome; this potential use is being investigated further in ongoing studies. Thus, darbepoetin alfa is an attractive therapy option for patients with chemotherapy or cancer-induced anemia. It allows increased flexibility and simplified dosing and may offer some benefit in the treatment of anemia in patients with myelodysplastic syndrome.

Topics: Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Humans; Myelodysplastic Syndromes; Neoplasms; Recombinant Proteins

Anabolic steroid and peptide hormones or growth factors are utilized to increase the performance of athletes of professional or amateur sports. Despite their well-documented adverse effects, the use of some of these agents has significantly grown and has been extended also to non-athletes with the aim to improve appearance or to counteract ageing. Pre-clinical studies and epidemiological observations in patients with an excess of hormone production or in patients chronically treated with hormones/growth factors for various pathologies have warned about the potential risk of cancer development and progression which may be also associated to the use of certain doping agents. Anabolic steroids have been described to provoke liver tumours; growth hormone or high levels of its mediator insulin-like growth factor-1 (IGF-1) have been associated with colon, breast, and prostate cancers. Actually, IGF-1 promotes cell cycle progression and inhibits apoptosis either by triggering other growth factors or by interacting with pathways which have an established role in carcinogenesis and cancer promotion. More recently, the finding that erythropoietin (Epo) may promote angiogenesis and inhibit apoptosis or modulate chemo- or radiosensitivity in cancer cells expressing the Epo receptor, raised the concern that the use of recombinant Epo to increase tissue oxygenation might favour tumour survival and aggressiveness. Cancer risk associated to doping might be higher than that of patients using hormones/growth factors as replacement therapy, since enormous doses are taken by the athletes often for a long period of time. Moreover, these substances are often used in combination with other licit or illicit drugs and this renders almost unpredictable all the possible adverse effects including cancer. Anyway, athletes should be made aware that long-term treatment with doping agents might increase the risk of developing cancer.

Topics: Anabolic Agents; Cell Transformation, Neoplastic; Doping in Sports; Erythropoietin; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Neoplasms; Recombinant Proteins; Risk Assessment; Steroids

To assess the effectiveness and cost-effectiveness of epoetin alpha, epoetin beta and darbepoetin alpha (referred to collectively in this report as epo) in anaemia associated with cancer, especially that attributable to cancer treatment.. Electronic databases were searched from 2000 (1996 in the case of darbepoetin alpha) to September 2004.. Using a recently published Cochrane review as the starting point, a systematic review of recent randomised controlled trials (RCTs) comparing epo with best standard was conducted. Inclusion, quality assessment and data abstraction were undertaken in duplicate. Where possible, meta-analysis was employed. The economic assessment consisted of a systematic review of past economic evaluations, an assessment of economic models submitted by the manufacturers of the three epo agents and development of a new individual sampling model (the Birmingham epo model).. In total 46 RCTs were included within this systematic review, 27 of which had been included in the Cochrane systematic review. All 46 trials compared epo plus supportive care for anaemia (including transfusions), with supportive care for anaemia (including transfusions), alone. Haematological response (defined as an improvement by 2 g/dl(-1)) had a relative risk of 3.4 [95% confidence interval (CI) 3.0 to 3.8, 22 RCTs] with a response rate for epo of 53%. The trial duration was most commonly 16-20 weeks. There was little statistical heterogeneity in the estimate of haematological response, and there were no important differences between the subgroups examined. Haemoglobin (Hb) change showed a weighted mean difference of 1.63 g/dl(-1) (95% CI 1.46 to 1.80) in favour of epo. Treatment with erythropoietin in patients with cancer-induced anaemia reduces the number of patients who receive a red blood cell transfusion (RBCT) by an estimated 18%. Health-related quality of life (HRQoL) data were analysed using vote counting and qualitative assessment and a positive effect was observed in favour of an improved HRQoL for patients on epo. Published information on side-effects was of poor quality. New trials provided further evidence of side-effects with epo, particularly thrombic events, but it is still unclear whether these could be accounted for by chance alone. The results of the previous Cochrane review had suggested a survival advantage for epo (HR 0.84, 95% CI 0.69 to 1.02), based on 19 RCTs. The update, based on 28 RCTs, suggests no difference (HR 1.03, 95% CI 0.88 to 1.21). Subgroup analysis suggested some explanations for this heterogeneity, but it is difficult to draw firm conclusions without access to the substantial amounts of missing or unpublished data, or more detailed results from some of the trials with heterogeneous patient populations. The conclusions are, however, broadly in line with those of a Food and Drug Administration (FDA) safety briefing, which recommended that patients with a haemoglobin above 12 g/dl(-1) should not be treated; the target rate of rise in Hb should not be too great, and further carefully conducted trials are required to determine which subgroups of patients may be harmed by the use of these products, in particular through the stimulation of tumour activity. Five published economic evaluations identified from the literature had inconsistent results, with estimates ranging from a cost per quality-adjusted life-year (QALY) u. Epo is effective in improving haematological response and reducing RBCT requirements, and appears to have a positive effect on HRQoL. The incidence of side-effects and effects on survival remains highly uncertain. However, if there is no impact on survival, it seems highly unlikely that epo would be considered a cost-effective use of healthcare resources. The main target for further research should be improving estimates of impact on survival, initially through more detailed secondary research, such as the individual patient data meta-analysis started by the Cochrane group. Further trials may be required, and have been recommended by the FDA, although many trials are in progress, completed but unreported or awaiting mature follow-up. The Birmingham epo model developed as part of this project contains new features that improve its flexibility in exploring different scenarios; further refinement and validation would therefore be of assistance. Finally, further research to resolve uncertainty about other parameters, particularly quality of life, adverse events, and the rate of normalisation, would also be beneficial.

Topics: Anemia; Antineoplastic Agents; Cost-Benefit Analysis; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Analysis; Treatment Outcome

Two independent reviewers used the methodological criteria published by the ISPOR Task Force on Retrospective Data to assess the quality of four posters presenting the results of retrospective database studies on the use of erythropoiesis-stimulating agents (epoetin alfa, epoetin beta, or darbepoetin alfa) for treating patients with cancer. A third reviewer consolidated the results. Overall, from the information reported in the four posters, their methodological quality ranged from poor to very poor; only a few of the criteria were satisfactorily addressed. The quality of the data sources and the research design received very poor scores. Key elements such as selection bias were not considered. These findings caution against the use of posters without appropriate assessment of their methodological quality. The ISPOR guidelines for the evaluation of retrospective analyses are a useful tool for assessing the quality of scientific posters.

Topics: Anemia; Antineoplastic Agents; Benchmarking; Darbepoetin alfa; Data Interpretation, Statistical; Epoetin Alfa; Erythropoietin; Guidelines as Topic; Hematinics; Humans; Neoplasms; Recombinant Proteins; Research Design; Technology Assessment, Biomedical

Erythropoietin emerged as the biggest drug in oncology despite never having demonstrated a survival benefit in patients with cancer. Two phase III clinical trials reported more than 3 years ago that erythropoietin adversely affected cancer survival rates, due mainly to tumor progression. Despite changes to the product label for erythropoietins in 2004, clinical practice remained unchanged until recent weeks when, following reports of three new phase III studies and a phase II trial, a "black box warning" for erythropoietin products was issued by the Food and Drug Administration (FDA). Whether erythropoietin products can be considered safe when used for FDA-approved indications is currently at issue; however, addressing this question will be difficult until the mechanisms of erythropoietin-stimulated tumor progression are understood. A thorough evaluation of materials from clinical trials already completed may shed new light on how erythropoietin promotes cancer progression. Until these issues are resolved, oncologists should inform their patients of erythropoietin's potential adverse impact on cancer progression and survival. Disclosure of potential conflicts of interest is found at the end of this article.

Topics: Anemia; Clinical Trials, Phase III as Topic; Contraindications; Disease Progression; Erythropoietin; Health Planning Guidelines; Humans; Neoplasms

Anemia is a decrease in circulating red blood cells that contributes to a complex group of symptoms. Anemia may be present in more than half of all patients with cancer but often is assessed, documented, prevented, and treated inadequately. Individuals with cancer are living longer, and the number of cancer treatment options provided at various points in the cancer continuum is growing; however, many treatments contribute to anemia. Because anemia can develop from multiple causes, treatment must be tailored to the underlying etiology. Cancer-related anemia can significantly affect therapeutic outcomes and patients' quality of life. Therapeutic interventions may include blood transfusions, administration of recombinant human erythropoietin, and interventions to support patient symptoms, most significantly, fatigue. Oncology nurses play a central role in risk assessment, symptom management, treatment planning, and evaluation and therefore must understand the etiology and physiology of cancer-related anemic states as well as evidence-based interventions to ensure optimal outcomes.

Topics: Algorithms; Anemia; Blood Transfusion; Causality; Cost of Illness; Decision Trees; Diagnosis, Differential; Erythropoietin; Evidence-Based Medicine; Fatigue; Hematinics; Hematocrit; Hemoglobins; Humans; Neoplasms; Nurse's Role; Nursing Assessment; Oncology Nursing; Patient Care Planning; Patient Education as Topic; Quality of Life; Risk Assessment

Anemia is frequently diagnosed in patients with cancer and its treatment is an important clinical problem. The deficiency in red blood cells (RBCs) can be a debilitating problem, and anemia correlates with poor performance status, deteriorates quality of life, and may negatively influence the prognosis of cancer patients. The development of recombinant human erythropoietins (rhEPO) provides a therapeutic option in patients with mild to moderate anemia. However, clinical experience demonstrates that more than half of anemic cancer patients are not treated. There is clear evidence that rhEPO reliably increases haemoglobin (Hb) levels in patients suffering from cancer-related or treatment-associated anemia. The dosing and management of these patients should strictly follow evidence-based guidelines of the clinical societies, as well as the manufacturer's recommendations. Furthermore, treatment of patients beyond the correction of anemia must be regarded as potentially harmful and should only be conducted in an experimental clinical setting. In this review, recently published recommendations and standards for the use of rhEPO will be discussed.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Hemoglobins; Humans; Neoplasms; Practice Guidelines as Topic; Recombinant Proteins; Survival Analysis

Erythropoietin (EPO) has been used clinically both as an erythropoietic stimulating agent in the treatment of anemia and as a tissue-protective agent in diverse clinical settings including stroke, multiple sclerosis, acute myocardial infarction and others. However, use of EPO or EPO-analogues leads to simultaneous targeting of both the erythropoietic and tissue-protective properties of EPO, and this strategy has been associated with several problems. Specifically, the benefit of correction of cancer-related anemia can be offset by the tissue-protective effects of EPO, which may lead to stimulation of cancer cell proliferation. Conversely, the benefit of tissue-protection in patients with stroke or myocardial infarction can be offset by adverse effects associated with the erythropoietic effects of EPO such as elevation of red blood cell mass, hypertension and prothrombotic phenomena. The finding that the erythropoietic and tissue-protective properties of EPO are conferred via two distinct receptor systems raises the interesting possibility of discovering novel drugs that selectively stimulate either the erythropoietic or the tissue-protective activities of EPO. This article reviews the current status of the clinical use of EPO and EPO-analogues in the treatment of cancer-related anemia and for tissue protection, outlines the distinct molecular biology of the tissue-protective and erythropoietic effects of EPO and discusses strategies of selective targeting of these activities with the goal of exploiting the full therapeutic potential of EPO.

Topics: Anemia; Animals; Erythropoiesis; Erythropoietin; Hematinics; Humans; Neoplasms; Receptors, Erythropoietin; Recombinant Proteins

Standing orders serve an important role in various healthcare settings by empowering nurses to implement certain procedures and activities on behalf of physicians, enabling more immediate interventions, and ultimately improving patient care. Standing orders are based on established clinical practice guidelines and are well suited for supportive interventions. Several evidence-based clinical practice guidelines are available for the treatment of anemia in patients with cancer. The guidelines can serve as a basis for the development of standing orders for the management of treatment-related anemia in patients with cancer, which will enable the delivery of consistently high-quality care to patients. A major advantage to the implementation of standing orders is that patients with suboptimal hemoglobin levels can be treated by oncology nurses in a timely manner and receive high-quality care that is consistent with available clinical evidence.

Topics: Algorithms; Anemia; Clinical Protocols; Decision Trees; Drug Monitoring; Epoetin Alfa; Erythropoietin; Evidence-Based Medicine; Ferritins; Hematinics; Hemoglobins; Humans; Iron; Iron-Binding Proteins; Mass Screening; Neoplasms; Nurse's Role; Nursing Assessment; Oncology Nursing; Patient Care Team; Practice Guidelines as Topic; Professional Autonomy; Quality Assurance, Health Care; Recombinant Proteins; Safety Management; Transferrin

Oxygen plays a direct role in cell death after exposure to ionizing radiations and tumour hypoxia, favoured by anaemia, is a factor of poor treatment response. Tumour phenotype is directly influenced by tissue oxygenation, inducing tumour cells adaptation to the environment and potential resistance to treatment. The correction of tumour hypoxia can increase treatment response. It is however difficult to directly correlate pO2 and vascularisation. Vessels from angiogenesis get endothelial cells but have lost the functions of normal vessels (receptors, muscles...). The role of angiogenesis has been demonstrated on initial tumour growth and on metastatic potential and regulation. Many pre clinical studies have demonstrated the benefit of combining anti angiogenic compounds and cytotoxic agents (chemotherapy drugs and ionizing radiations). Clinical studies are on going and new evaluation models of treatment response will be necessary.

Topics: Anemia; Angiogenesis Inhibitors; Animals; Cell Hypoxia; Combined Modality Therapy; Endothelium, Vascular; Erythropoietin; Humans; Neoplasms; Neovascularization, Pathologic; Oxygen; Oxygen Consumption; Partial Pressure; Radiation Tolerance; Recombinant Proteins

Due to concerns related to treatment with erythropoietin (EPO) and possible negative effects on tumour control, a workshop was organised by the Medical Products Agency of Sweden with the aim to revise national treatment guidelines if needed. In patients with solid tumours, conflicting results have been reported with respect to tumour control and survival. Until further notice it is therefore recommended that EPO should be used restrictively in the treatment of patients with cancer and that the anticipated improvement in quality of life should be evaluated against potential risks.

Topics: Anemia; Contraindications; Erythropoietin; Female; Hematinics; Humans; Male; Neoplasms; Practice Guidelines as Topic; Receptors, Erythropoietin; Survival Analysis; Sweden; Treatment Failure

At present, anaemia in the patients with cancer remains a problem of the first magnitude and of increasing interest due to the high incidence, the major knowledge of its physiopathology, the negative impact on the quality of life of the patient, the influence on the evolution of the disease and its treatments and, finally to the progressive development of new alternatives of treatment, especially the erythropoietic agents. For all this, it becomes necessary to consider the treatment of the anemia of the patients with cancer as a basic part of their support treatment. The erythropoietic agents have demonstrated in the last years that constitute a therapeutic alternative to obtain an increase of the levels of hemoglobin in the patients with anticancer treatments, considering specially that the correction of the anemia not only represents the improvement of an analytical value but also has a significant impact on the quality of life of the patients and diminishes the transfusion requirements. Erythropoietic proteins available for the treatment of the anemia of the patients with cancer are Epoetin-alpha, Epoetin-beta and Darbepoetin-alpha. The existence of different drugs, different doses and intervals of administration, clinical different situations and heterogeneous studies, made necessary the development of documents of consensus and guides of clinical recommendations which provide information on the scientific evidence that supports the use of these agents in medical care. This paper summarizes the main recommendations from panels of experts and scientific societies published so far.

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Hematinics; Humans; Neoplasms; Practice Guidelines as Topic; Societies, Scientific

Advanced age alone should never be the reason for refusing elderly people an effective oncological therapy which could improve their quality of life and possibly also meaningfully extend their survival. However, age-related physiological organ changes and potential cognitive, emotional and social problems must be precisely analyzed before beginning a therapy. Only then can a decision be made for a specific tumour therapy or perhaps symptom management with supportive measures. Treatability is evaluated using test instruments that have been developed for geriatric assessment.

Topics: Age Factors; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Erythropoietin; Geriatric Assessment; Humans; Life Expectancy; Middle Aged; Neoplasms; Palliative Care; Patient Selection; Prognosis; Quality of Life; Risk Factors

Anemia is a frequent problem in cancer patients, especially in those treated with chemotherapy, and has an important negative impact on quality of life. Red blood cell transfusions provide clear but rather temporary comfort. The development of erythropoietic stimulating agents (ESAs) led to a more durable anemia treatment. Darbepoetin alpha is a unique ESA with a long plasma half life, thereby suitable for administration with different dosing intervals. Apart from administration every week, darbepoetin alpha also proved to be efficient in reducing red blood cell transfusion rates and in improving health-related quality of life when administered at a dose of 500 microg once every 3 weeks. This is a convenient therapy schedule because it can be synchronized with the chemotherapy cycle in many patients. Recently, concerns have been raised about the long-term safety of ESAs, more specifically about their effect on survival. Available data must be interpreted with caution, but at present there is no clear evidence to support a negative effect on outcome with darbepoetin alpha therapy when used according to the guidelines for treatment of chemotherapy-induced anemia. Further studies focusing on survival as the primary end point are ongoing.

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Clinical Trials as Topic; Combined Modality Therapy; Darbepoetin alfa; Drug Administration Schedule; Drug Approval; Erythropoietin; Humans; Injections, Intravenous; Injections, Subcutaneous; Iron-Dextran Complex; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Thromboembolism

Anaemia has a high incidence in cancer patients, especially when it is a consequence of myelosuppressive treatments. The incidence and prevalence of this condition is influenced by the type and extension of the tumour, type and intensity of the myelosuppressive treatment that patients receive, and previous surgery or intercurrent infections. Clinical manifestations of anaemia, overlapped by tumour symptomatology, depend on haemoglobin (Hb) levels; these manifestations cause impairment of the functional capacity, as well as a negative impact on the quality of life (QOL) of cancer patients as a consequence. Erythropoietin treatment for anaemia has been established as optimal for correcting Hb levels. Its impact on patients' QOL has been evaluated in numerous randomised prospective studies by the use of diverse types of erythropoietin and administration modes. The three types of erythropoietin, alpha, beta and darbepoetin alpha, have shown a clear efficacy in all haematological parameters. This positive effect is related with significant improvements in the QOL of patients, especially those patients undergoing myelosuppressive treatments, and with regard to specific scales of fatigue and anaemia.

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Female; Humans; Male; Neoplasms; Quality of Life; Recombinant Proteins

Anaemia is a frequent complication in cancer patients and may be multifactorial in origin. Treatment with recombinant human erythropoietin (rHuEPO) is an alternative to red blood cell transfusion. The evidence from clinical trials has established that patients with chemotherapy-induced anaemia with a haemoglobin concentration below 10 g/dl benefit from epoetin therapy. The native glycoprotein hormone consists of 165 amino acids with three N-glycosylation and one O-glycosylation sites. Epoetin and darbepoetin bind to the EPO receptor to induce intracellular signalling by the same intracellular molecules as native EPO. There are some differences in the glycosylation pattern which lead to variations in the pharmacokinetics and pharmacodynamics profiles. Pharmacokinetic and therapeutic studies have examined the use of rHuEPO administered intravenously and subcutaneously and there is accumulating evidence that the latter route has several advantages in cancer patients. After subcutaneous administration, the bioavailability of epoetin is about 20-30% and has a plasma half-life of >24 h. Darbepoetin has a longer half-life after subcutaneous administration of 48 h. The general recommendations are based on evidence from trials in which epoetin was administered 150 U/kg thrice weekly. The recommended initial dose for darbepoetin alpha is 2.25 mug/kg per week. The most serious adverse effects are hypertension, bleeding and increased risk of thrombotic complications. Caution is advised when used in patients who are at high risk for thromboembolic events. In the management of anaemic cancer patients, physicians should closely follow the National Comprehensive Cancer Network (NCCN) and American Society of Clinical Oncology (ASCO)/American Society of Hematology (ASH) guidelines.

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Neoplasms; Recombinant Proteins

Topics: Erythropoietin; Humans; Neoplasms; Practice Guidelines as Topic; Recombinant Proteins; Treatment Outcome

Recombinant human erythropoietins (rhEPO) reliably increase hemoglobin levels in cancer patients experiencing chemotherapy-associated anemia. However, in patients with "anemia of cancer" not being treated with chemotherapy, rhEPO appears less effective. Recently, two studies have been broadly discussed which have raised concern on the concomitant use of erythropoietin and chemo- or radiation therapy in cancer patients. In addition, use of rhEPO is generally not considered cost-effective. Thus, the application of rhEPO should be limited to indications with proven clinical benefit. This review will provide an overview of the state of the art use of rhEPO in anemic patients and will discuss future developments.

Topics: Anemia; Bone Marrow Transplantation; Clinical Trials as Topic; Cost-Benefit Analysis; Erythropoietin; Female; Humans; Male; Myelodysplastic Syndromes; Neoplasms; Recombinant Proteins

Anaemia is a common occurrence in patients with cancer, resulting in symptoms such as fatigue that have a profound impact on quality of life. Anaemia is also associated with poor treatment outcome and overall survival. Epoetin beta, a recombinant human erythropoietin that has the same structure and function as the endogenous hormone, is an effective and safe treatment of cancer-related anaemia. Various studies in patients with solid tumours have shown that this agent effectively increases haemoglobin levels and reduces the need for emergency blood transfusions regardless of the type of concomitantly administered chemotherapy. Epoetin beta also improves the quality of life of anaemic patients with cancer, decreasing fatigue and improving the ability to perform usual daily activities. In addition, epoetin beta prevents severe anaemia and reduces transfusion requirements in patients with a high-risk of developing anaemia during chemotherapy, such as those receiving platinum-based regimens. A meta-analysis of epoetin beta trials showed that epoetin beta has no negative impact on survival or thrombosis-related survival and may reduce the risk of tumour progression in patients with solid or lymphoid malignancies. Another study has shown epoetin beta to be equally effective when administered once weekly or three times weekly. Therefore, epoetin beta offers an effective, safe and convenient therapy for the management of anaemia in patients with cancer.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Anaemia and associated fatigue are common problems in patients with cancer, and fatigue is considered by patients with cancer to be their most limiting symptom. The introduction of erythropoiesis-stimulating proteins (ESPs) has greatly improved the management of anaemia; however, many European patients with cancer-related anaemia are untreated because of a lack of awareness among healthcare professionals of the benefits of anaemia treatment to patients, or because of regional differences in treatment practices. Recently, the European Organisation for Research and Treatment of Cancer (EORTC) developed the first European evidence-based guidelines for the use of ESPs in cancer-related anaemia in order to facilitate and standardize the assessment and management of the condition. These guidelines, and the implications for oncology nurses in implementing them in practice, are discussed.

Topics: Algorithms; Anemia; Decision Trees; Diagnosis, Differential; Documentation; Drug Administration Schedule; Drug Monitoring; Erythropoietin; Evidence-Based Medicine; Fatigue; Hemoglobins; Humans; Neoplasms; Nurse's Role; Nursing Assessment; Oncology Nursing; Patient Education as Topic; Patient Selection; Practice Guidelines as Topic

In recent years there has been an increasing debate regarding the benefits of initiating erythropoietic treatment in patients with cancer when anemia is still relatively mild. To address this, a systematic review of studies was conducted that answered the following question: Is there a clinical benefit associated with early erythropoietic intervention (hemoglobin > or = 10 g/dL) for chemotherapy-induced anemia?. A systematic review of published literature and meeting abstracts was undertaken to identify relevant studies. Data were extracted from studies meeting prespecified eligibility criteria. For outcome measures not associated with significant heterogeneity, summary measures of relative risk associated with early erythropoietic intervention were estimated using the method of Mantel and Haenszel.. Eleven studies were eligible and were included in the review. Erythropoietic treatment effectively decreased transfusion incidence and the proportion of patients with hemoglobin < 10 g/dL compared with no treatment, with relative risk reductions of 0.50 (95% confidence interval [CI], 0.43, 0.59; 7 studies, P < 0.0001) and 0.40 (95% CI, 0.19, 0.83; 4 studies, P = 0.147), respectively. The findings from both prospective studies and planned subset analyses in which early and late intervention were compared also indicated a reduction in the relative risk of both transfusions and hemoglobin < 10 g/dL after early intervention (0.55 [95% CI, 0.42, 0.73; 5 studies, P < 0.0001] and 0.44 [95% CI, 0.33, 0.57; 2 studies, P < 0.0001], respectively).. Collectively, these findings suggest that optimal clinical benefit from erythropoietic treatment of chemotherapy-induced anemia may be achieved through early intervention.

Topics: Anemia; Antineoplastic Agents; Erythrocyte Transfusion; Erythropoietin; Hemoglobins; Humans; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic

To review and compare the data concerning the clinical activity of epoetin alfa versus darbepoetin alfa when administered to patients with cancer who are experiencing treatment-related anemia.. English-language publications from the MEDLINE database (1990-June 2005), published articles, and meeting abstracts were reviewed.. Relevant data were extracted from published reports and abstracts on studies of humans with cancer who developed treatment-related anemia and were treated with epoetin alfa or darbepoetin alfa.. Epoetin alfa and darbepoetin alfa are similar agents with identical indications for treatment of anemia in patients with cancer. Clinical trials have demonstrated that both agents can significantly improve hemoglobin levels, reduce transfusion requirements, and improve quality of life. Epoetin alfa is approved for administration at a dose of 150 units/kg subcutaneously 3 times per week, and darbepoetin alfa is approved for administration at a dose of 2.25 units/kg once a week. Clinical studies have demonstrated that epoetin alfa may be administered at 40,000 units once a week and that darbepoetin alfa may be administered at 200 microg every 2 weeks without loss of efficacy. Cost analysis, based on the average wholesale price of each drug alone administered for 12 weeks at Food and Drug Administration-approved doses, revealed that epoetin alfa is less expensive than darbepoetin alfa. When they are administered in the extended schedules, the cost of darbepoetin alfa is slightly less than that of epoetin alfa. However, the total expense associated with the extended schedule of either agent is further reduced by a reduction in other costs associated with drug administration.. Epoetin alfa and darbepoetin alfa have identical indications for treatment of anemia in patients receiving cancer chemotherapy. Clinical trials have demonstrated similar activities with both agents. Darbepoetin alfa, with a longer half-life, can be administered less frequently, saving costs as well as reducing patient office visits.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

The introduction of recombinant human erythropoietin to the management of anemia in cancer patients has resulted in significant reductions in allogeneic blood transfusions, while at the same time contributing to improvements in quality of life. A recent meta-analysis of five randomized, placebo-controlled trials with patient-level data revealed that, while epoetin alfa was very effective in reducing transfusions compared with placebo, patients who were pretransfused were twice as likely to subsequently be transfused during epoetin alfa treatment.. To further assess the validity of this rather provocative concept, another integrated analysis was conducted with patient-level data from three Canadian trials, with a combined total of 665 patients receiving epoetin alfa treatments for their cancer- and chemotherapy-induced anemia.. Once again, pretransfusion was the most significant baseline predictor of transfusion, with patients that were pretransfused having a significantly greater likelihood of being transfused than their transfusion-naive counterparts. Furthermore, and corroborating previous findings, baseline hemoglobin (Hb) level was again found to be a significant predictor of transfusion, with patients who were treated at a baseline Hb level < 10 g/dl having a higher chance of being transfused than patients in whom epoetin alfa was initiated at baseline Hb levels of 10-11 g/dl. In addition, when the total units transfused in patients receiving epoetin alfa at different baseline Hb levels were analyzed, >85% of the units of blood transfused were received by patients with baseline Hb levels < 10 g/dl.. These data strongly suggest that early treatment with epoetin alfa could significantly optimize clinical benefit in reducing the use of transfusion in cancer patients receiving chemotherapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Canada; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Neoplasms; Recombinant Proteins; Risk; Risk Factors; Time Factors

Erythropoietin (Epo) has long been known to be the principal hematopoietic growth factor that regulates cellular proliferation and differentiation along the erythroid lineage. Recent studies have shown that Epo is a pleiotropic cytokine that is proangiogenic and exerts broad tissue-protective effects in diverse nonhematopoietic organs. Recombinant Epo (rEpo) has been widely used in the clinic to prevent or treat malignancy-associated anemia. A series of clinical trials have documented the efficacy of rEpo in reducing RBC transfusion requirements and improving quality of life in cancer patients, and a recent meta-analysis suggested a positive effect on survival. However, two randomized trials reported negative outcomes with rEpo, as patients in the rEpo arm fared worse than their placebo-treated counterparts with respect to progression-free survival. The expression of Epo receptor (EpoR) in cancer cells has raised the possibility that exogenous rEpo may exert direct effects on tumor cells associated with the potential for stimulation of proliferation, inhibition of apoptosis, or modulation of sensitivity to chemoradiation therapy. The presence of an autocrine-paracrine Epo-EpoR system in tumors and potential effects of Epo on tumor microenvironment and angiogenesis are consistent with a complex biology for Epo-EpoR signaling in cancer that requires further research. This review describes Epo and EpoR biology, focusing on the pleiotropic effects of Epo on nonhematopoietic tissues as well as the expression and function of EpoR in cancer cells.

Topics: Erythropoietin; Humans; Neoplasms; Receptors, Erythropoietin; Recombinant Proteins; Signal Transduction

Topics: Anemia; Erythrocyte Transfusion; Erythropoietin; Evidence-Based Medicine; Humans; Meta-Analysis as Topic; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins

For cancer patients, anemia can be a debilitating problem that negatively influences their overall quality of life and worsens their prognosis. The condition is caused either by the cancer itself or by cytotoxic treatment. Anemia is the primary indication for transfusion of red blood cells, but the development of recombinant human erythropoietins (epoetins) provides an alternative to red blood cell transfusions. Treatment with epoetins has been shown to reduce transfusion rates and increase hemoglobin response. There is some evidence that epoetins improve quality of life. It remains unclear, however, whether erythropoietin affects tumor growth and survival, and this area requires further investigation. Data from clinical trials suggest that erythropoietin increases the risk of thromboembolic complications. In the management of anemic patients, physicians should follow closely the dosing recommendations in products' package inserts or the ASCO/American Society of Hematology guidelines. Treatment of patients beyond the correction of anemia, however, has to be regarded as experimental and is potentially harmful, so should only be conducted in clinical trials.

Topics: Anemia; Darbepoetin alfa; Erythropoietin; Humans; Neoplasms; Practice Guidelines as Topic; Quality of Life; Recombinant Proteins; Survival Analysis

Recombinant human erythropoietin (rHuEpo) has become the most widely used cytokine in the world. Following the success of its use in patients with end-stage renal disease, the usefulness of rHuEpo to ameliorate other anemias was assessed, including pediatric patients and newborn infants. The treatment or prevention of anemia of prematurity with rHuEpo resulted in a significant reduction in the number of transfusions and donor exposure. A clear definition of which premature babies must receive therapy needs yet to be established. Other indications in neonatal period include hyporegenerative and hemolytic anemias. With the exception of chronic renal failure, in older children the efficacy of rHuEpo has not been evaluated as in adults. While an impressive amount of studies were carried out during the last years in adult patients with cancer-related or HIV-infection-related anemias, allowing to establish clear conclusions on its efficacy, only a few trials with small number of patients have been reported in children. Up to date, results in pediatric patients suggest that rHuEpo therapy is as useful as in adult patients, but prospective, randomized trials including large number of patients are essential to achieve definitive conclusions. Results of studies designed to evaluate the efficacy of rHuEpo for sustaining an adequate dose of ribavirin in patients receiving treatment for hepatitis C are encouraging. The potential for use of the non-hematopoietic effects of rHuEpo in newborn infants is a novel and exciting issue. The role of rHuEpo as a tissue protective factor for central nervous system and intestinal mucosa is under exhaustive investigation.

Topics: Adult; Anemia; Anemia, Neonatal; Child; Child, Preschool; Erythropoietin; Hepatitis C; HIV Infections; Humans; Infant; Infant, Newborn; Infant, Postmature; Neoplasms; Recombinant Proteins; Renal Dialysis; Renal Insufficiency

Anemia is highly prevalent in patients with cancer and its impact on quality of life and long-term outcome in these patients is well documented. Recombinant human erythropoietins, or epoetins, have been used to treat cancer-related or antitumor therapy-induced anemia for many years. Through a combination of clinical studies and extensive experience in the real-life clinical setting, epoetin beta has been shown to be efficacious and well tolerated, increasing hemoglobin levels, reducing the need for transfusion and improving quality of life. This favorable efficacy and safety profile has been demonstrated across a broad range of malignancy types, irrespective of the treatment used (platinum or non-platinum based). The effect of treatment with epoetin beta is rapid, with mean hemoglobin increases of 1 g/dl seen as early as 4 weeks following the start of therapy. Furthermore, there is no evidence that epoetin beta negatively affects overall survival or tumor progression in anemic patients with cancer. The approved 30,000 IU once-weekly dosing regimen (as opposed to the 10,000 IU three-times weekly regimen) provides greater convenience and may result in improved treatment compliance.

Topics: Epoetin Alfa; Erythropoietin; Hematologic Neoplasms; Hemoglobins; Humans; Medical Oncology; Neoplasms; Recombinant Proteins

Topics: Anemia; Blood Transfusion; Erythropoietin; Female; History, 20th Century; Humans; Male; Neoplasms; Recombinant Proteins

This is an updated systematic review of 57 trials and 9353 cancer patients from articles, abstracts, and reports published between January 1, 1985, and April 30, 2005, on the effects of epoetin alfa and beta (i.e., epoetin) and darbepoetin alfa (i.e., darbepoetin). We included randomized controlled trials comparing epoetin or darbepoetin plus red blood cell transfusion with red blood cell transfusion alone for prophylaxis or treatment of anemia in cancer patients with or without concurrent antineoplastic therapy. The Cochrane Library, MEDLINE, EMBASE, and conference proceedings were searched. Effect estimates and 95% confidence intervals (CIs) were calculated with fixed-effects models. Treatment with epoetin or darbepoetin statistically significantly reduced the risk for red blood cell transfusions (relative risk [RR] = 0.64, 95% CI = 0.60 to 0.68; 42 trials and 6510 patients) and improved hematologic response (RR = 3.43, 95% CI = 3.07 to 3.84; 22 trials and 4307 patients). Treatment with epoetin or darbepoetin increased the risk of thrombo-embolic events (RR = 1.67, 95% CI = 1.35 to 2.06; 35 trials and 6769 patients). Uncertainties remain as to whether and how epoetin or darbepoetin affects overall survival (hazard ratio = 1.08, 95% CI = 0.99 to 1.18; 42 trials and 8167 patients). Caution is advised when using epoetin or darbepoetin in combination with thrombogenic chemotherapeutic agents or for cancer patients who are at high risk for thrombo-embolic events.

Topics: Anemia, Hypochromic; Antineoplastic Agents; Darbepoetin alfa; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Hematinics; Humans; Incidence; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Research Design; Risk Assessment; Thromboembolism; Treatment Outcome

Darbepoetin alfa (Aranesp) is an analogue of recombinant human erythropoietin (rHuEPO) produced using recombinant DNA technology. The high number of sialic acid moieties in darbepoetin alfa results in a prolonged half-life and enhanced in vivo biological activity compared with rHuEPO (as demonstrated in animal studies) and permits a reduction in the frequency of administration. Subcutaneous darbepoetin alfa 2.25 microg/kg once weekly or 500 microg once every 3 weeks (with a provision for dose adjustments) is an effective and well tolerated erythropoietic agent in anaemic patients with cancer receiving chemotherapy. In randomised, controlled clinical trials, the drug increased haemoglobin levels and reduced the need for blood transfusions in patients with various types of nonmyeloid malignancies and also ameliorated anaemia-related fatigue, thereby improving their health-related quality of life (HR-QOL) scores. The once-every-3-weeks dosage regimen provides further convenience by offering the possibility of synchronising its administration with most chemotherapy regimens. Direct comparisons between approved dosages of darbepoetin alfa and other erythropoietic agents have not been conducted. Such comparisons would be very helpful in formulating definitive conclusions about their relative efficacy and cost effectiveness. Darbepoetin alfa provides an effective and well tolerated treatment option for the treatment of anaemia in patients with cancer receiving chemotherapy.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Erythropoietin; Humans; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome

Hypoxia is now recognized as a major explanation of tumor radioresistance and is an important prognostic factor in head and neck and cervical cancers. Anemia, which had also a negative impact on cancer prognosis, increase tumor hypoxia. But we do not know actually if anemia has a direct role in tumor resistance or if it only reflect aggressiveness of the disease. Some trials have demonstrated that erythropoietin could increase the hemoglobin level during radiation courses. The only published randomised trial, performed in head and neck cancers, did not find any benefit for erythropoietin ; moreover, a deleterious effect was demonstrated. Possible explanations for this paradoxal result were discussed, particularly biological hypothesis and statistical bias.

Topics: Anemia; Blood Transfusion; Cell Hypoxia; Erythropoietin; Hematinics; Humans; Neoplasms; Otorhinolaryngologic Neoplasms; Radiation Tolerance; Randomized Controlled Trials as Topic; Recombinant Proteins

Topics: Anemia; Antineoplastic Agents; Dose-Response Relationship, Drug; Erythropoiesis; Erythropoietin; Humans; Neoplasms

Anaemia associated with cancer and cancer therapy is an important clinical factor in the treatment of malignant diseases. Therapeutic alternatives are recombinant human erythropoietin (Epo), darbepoetin (Darbepo) and red blood cell transfusions.. The aim of this systematic review was to assess the effects of Epo or Darbepo to either prevent or treat anaemia in cancer patients.. We searched the Central Register of Controlled Trials, MEDLINE and EMBASE and other data bases. Searches were done for the periods 01/1985 to 12/2001 for the first review and 1/2002 to 04/2005 for the update. We also contacted experts in the field and pharmaceutical companies.. Randomised controlled trials on managing anaemia in cancer patients that compared the use of Epo/Darbepo (plus transfusion if needed) with observation until red blood cell transfusion was required.. Several reviewers independently assessed trial quality and extracted data.. This update of the systematic review included a total of 57 trials with 9,353 patients. Of these, 27 trials with 3,287 adults were also included in the first Cochrane Review. Thirty trials with 6,066 patients were added during the update process. Use of Epo/Darbepo significantly reduced the relative risk of red blood cell transfusions (RR 0.64; 95% CI 0.60 to 0.68, 42 trials, n = 6,510). On average participants in the Epo/Darbepo group received one unit of blood less than the control group (WMD -1.05; 95% CI -1.32 to -0.78, 14 trials, n = 2,353). For participants with baseline haemoglobin below 12 g/dL haematological response was observed more often in participants receiving Epo/Darbepo (RR 3.43; 95% CI 3.07 to 3.84, 22 trials, n = 4,307). There was suggestive evidence that Epo/Darbepo may improve Quality of Life (QoL). The relative risk for thrombo embolic complications was increased in patients receiving Epo/Darbepo compared to controls (RR 1.67, 95% CI 1.35 to 2.06; 35 trials, n = 6,769). Uncertainties remain whether and how Epo/Darbepo effects tumour response (fixed effect RR 1.12; 95% CI 1.01 to 1.23, 13 trials, n = 2,833; random effects: RR 1.09; 95% CI 0.94 to 1.26) or overall survival (unadjusted and adjusted data: HR 1.08; 95% CI 0.99 to 1.18; 42 trials, n = 8,167).. There is consistent evidence that administration of Epo/Darbepo reduces the relative risk for blood transfusions and the number of units transfused in cancer patients. For patients with baseline haemoglobin below 12 g/dL (mild anaemia) there is strong evidence that Epo/Darbepo improves haematological response. There is suggestive evidence that Epo/Darbepo may improve QoL. However, there is strong evidence that Epo/Darbepo increases the relative risk for thrombo embolic complications. Whether and how Epo/Darbepo effects tumour response and overall survival remains uncertain.

Topics: Anemia; Darbepoetin alfa; Erythrocyte Transfusion; Erythropoietin; Humans; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins

Anemia is common in patients treated with chemotherapy for both solid and hematologic malignancies, contributing to fatigue and diminished quality of life and exposing them to the inherent risks of red blood cell transfusions. Erythropoiesis-stimulating proteins have been shown to increase hemoglobin levels, reduce the need for transfusions, and improve quality of life. The current practice guidelines recommend treating moderate to severe chemotherapy-induced anemia with erythropoiesis-stimulating proteins, but the risk of transfusions may be less with earlier intervention at higher hemoglobin levels. A review of the literature suggests that treating mild chemotherapy-induced anemia with erythropoiesis-stimulating proteins reduces the risks of transfusions and the development of more-severe anemia. Weighing the clinical evidence together with other clinical and economic considerations should provide greater insight into the benefits of treating mild anemia in patients treated with chemotherapy.

Topics: Anemia; Drug-Related Side Effects and Adverse Reactions; Epoetin Alfa; Erythropoiesis; Erythropoietin; Humans; Neoplasms; Recombinant Proteins; Time Factors

Chemotherapy-induced anemia is common in patients who have cancer. Erythropoiesis-stimulating proteins such as epoetin alfa (Procrit) and darbepoetin alfa (Aranesp) have been shown to improve hematologic and clinical outcomes in these patients. Darbepoetin alfa has a longer serum half-life than epoetin alfa, making less frequent administration possible and offering the possibility of synchronizing the administration of erythropoietic therapy and chemotherapy. Several clinical trials have evaluated the utility of darbepoetin alfa given every 3 weeks (q3wk) in patients with chemotherapy-induced anemia. An exploratory study showed that darbepoetin alfa q3wk stabilized hemoglobin levels and reduced transfusion requirements. It was also shown that giving darbepoetin alfa q3wk at the same time as the chemotherapy produced hematopoietic benefits similar to those observed when it is given later in the chemotherapy cycle. The q3wk dosing schedule was effective in patients with mild and moderate anemia, and treatment goals were achieved in most of them. The equivalence of q3wk and qwk darbepoetin alfa has also been established. Synchronous administration of darbepoetin alfa with chemotherapy is a convenient option for patients with chemotherapy-induced anemia, with clinical trials showing it to be an effective treatment strategy.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Hematinics; Humans; Neoplasms

Anemia is common in many patients with cancer treated with chemotherapy. One option for managing chemotherapy-induced anemia (CIA) is erythropoiesis-stimulating proteins (ESPs), which are indicated for the treatment of CIA in patients with most types of cancer. They have been shown to be safe and effective in numerous well-documented studies, and their side effects are well known. The rate of thrombotic events with the long-acting ESP darbepoetin alfa (Aranesp) has been consistent in studies conducted before and after its approval. The association of thrombotic events with high hemoglobin levels or rapid increases in its levels in patients with cancer remains controversial. Adjusting the dose of the ESP to maintain and monitor a target hemoglobin level of 11 to 12 g/dL is certainly prudent and may help prevent or minimize these events. Chemotherapy-induced anemia has been associated with shorter survival in patients with cancer, and the relation is likely multifactorial. Data on the treatment of CIA with ESPs have not shown a consistent effect on survival. Two studies in patients with hemoglobin levels above the target level showed that survival was shorter in the patients treated with ESPs. A review of data from other trials found no effect of ESPs on survival, and other trials suggested a positive effect. This article reviews data on survival in patients treated with ESPs and discusses five large randomized controlled trials of darbepoetin alfa that are addressing this issue.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Erythropoiesis; Erythropoietin; Hematinics; Humans; Neoplasms; Randomized Controlled Trials as Topic; Survival Rate

Topics: Anemia; Antiemetics; Antineoplastic Agents; Erythropoietin; Evidence-Based Medicine; Humans; Incidence; Nausea; Neoplasms; Nurse's Role; Oncology Nursing; Practice Guidelines as Topic; Quality of Life; Radiotherapy; Risk Factors; Stomatitis; Survivors; Vomiting

Oxygen deprivation leading to hypoxia is a common feature of solid tumours. Under these conditions a signalling pathway involving a key oxygen-response regulator termed the hypoxia-inducible factor (HIF) is switched on. HIF is a transcription factor that, in hypoxia, drives the induction or repression of a myriad of genes controlling multiple cell functions such as angiogenesis, metabolism, invasion/metastasis and apoptosis/survival. Thus, the level of oxygen in a cell dictates the molecular response of cells through modulation of gene expression. Here we review the central role of HIF in cancer progression through the tumour response to hypoxia. Within this context the following aspects will be discussed: i) the mechanism by which oxygen deprivation inhibits two oxygen-sensor hydroxylases, thereby releasing the alpha subunit of HIF from programmed destruction by the ubiquitin-proteasome system and from a lock on its transcriptional activity; ii) the way in which the bi-transcriptional activity of HIF-alpha, which is regulated by the interplay between an oxygen-sensor attenuator and co-activators, determines the repertoire of gene expression; and iii) the role that HIF plays in tumour metabolism, in particular in glycolysis, and consequent acidification of the microenvironment, which influences both cell survival and cell death. Finally, the direct link of HIF to tumourigenesis and metastasis will be investigated and approaches for fighting tumour progression through a better understanding of HIF-mediated modulation of tumour metabolism and cell death will be considered.

Topics: Cell Death; Cell Hypoxia; Cell Survival; Enzyme Stability; Erythropoietin; Gene Expression Regulation; Homeostasis; Hydroxylation; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic; Oxygen; Procollagen-Proline Dioxygenase; Vascular Endothelial Growth Factor A

To assess the early effect of epoetin beta on survival and tumour progression in anaemic patients with cancer, data were pooled from nine randomised clinical trials comparing epoetin beta with placebo or standard care. Studies were not primarily designed to assess these end points. Follow-up was for treatment duration plus 4 weeks following therapy completion. All adverse events (AEs) were retrospectively reviewed blinded, for progression. Thromboembolic events were also assessed. Data analysis involved standard statistical tests. Overall, 1413 patients were included (epoetin beta, n = 800; control, n = 613; 56% haematological, and 44% solid). Median initial epoetin beta dose was 30,000 IU/week. Overall survival during months 0-6 was similar with epoetin beta and control (0.31 vs 0.32 deaths/patient-year). No increased mortality risk was seen with epoetin beta (relative risk (RR) 0.97, 95% CI: 0.69, 1.36; P = 0.87). There was a significantly reduced risk of rapidly progressive disease for epoetin beta (RR 0.78, 95% CI: 0.62, 0.99; P = 0.042). Epoetin beta was associated with a slightly higher frequency of thromboembolic events vs control (5.9% vs 4.2% of patients) but thromboembolic-related mortality was identical in both groups (1.1%). Epoetin beta provided a slight beneficial effect on tumour progression and did not impact on early survival or thromboembolic-related mortality.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Disease Progression; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Rate

Recombinant human erythropoietin has become an essential part of the management of anemic patients with end-stage renal disease. It is also used to treat the anemia associated with cancer and other diseases, and it improves quality of life. In recent years, studies in animals and humans have focused on the use of rHuEPO for other indications. It has been found to play a role in both cardioprotection and neuroprotection. It has effects on the immune system, and can cause regression in hematologic diseases such as multiple myeloma. It may also improve the response of solid tumors to chemotherapy and radiation therapy. On the other hand, concerns have been raised following two studies of patients with solid tumors in whom those treated with rHuEPO had diminished survival. Criticism of the design of these studies makes it clear that large, well-designed, randomized trials must be performed to determine the role of rHuEPO in the treatment of cancer, and more generally to clarify the full clinical benefits of the drug, while minimizing the harm.

Topics: Anemia; Animals; Erythropoietin; Humans; Kidney Failure, Chronic; Mice; Neoplasms; Quality of Life; Recombinant Proteins

Erythropoietin (Epo) is the regulator of red blood cell formation. Its receptor (EpoR) is now found in many cells and tissues of the body. EpoR is also shown to occur in tumor cells and Epo enhances the proliferation of these cells through cell signaling. EpoR antagonist can reduce the growth of the tumor in vivo. In view of our current knowledge of Epo, its recombinant forms and receptor, use of Epo in cancer patients to enhance the recovery of hematocrit after chemotherapy treatment has to be carefully evaluated.

Topics: Animals; Cell Proliferation; Erythropoiesis; Erythropoietin; Humans; Neoplasms; Receptors, Erythropoietin; Recombinant Proteins; Signal Transduction

EPO is known as an inducer of maturation and proliferation of erythrocytes. Moreover, it favours angiogenesis. In several studies it was encountered that EPO is a trophic agent that mediates survival and inhibits apoptosis of hypoxia affected cells, particularly those which build masses of irregularly vascularized cancers. The main task concerning EPO for oncologists is the choice to give or not to give recombinant EPO to anemia endangered cancer patients. EPO can do the quality of life better and cause recovery from anemia post chemotherapy and radiation of cancer patients. Nevertheless, EPO therapy shortens survival of patients in some cancers, in which antiapoptotic effect of EPO predominates directly in malignant cells. Thus, separately in every type of cancer, therapeutic use of recombinant EPO calls for prior investigations, if EPO signaling causes proliferation of cancer cells by direct stimulation of EPOR positive malignant cells. Unless the proliferative effect of EPO on cancer cells is excluded, its use in the therapy of anemia in cancer patients is not quite safe.

Topics: Anemia; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Erythropoietin (Epo) is a pleiotropic agent, that is to say, it can act on several cell types in different ways. An independent system Epo/Epo receptor (EpoR) was detected in brain, leading to the hypothesis that this hormone could be involved in cerebral functions. Epo/EpoR expression changes during ontogenesis, thus indicating the importance of this system in neurodevelopment. Moreover, the hypoxia-induced production of Epo in the adult brain suggests that it could exert a neurotrophic and neuroprotective effect in case of brain injury. Epo could also influence neurotransmission, inducing neurotransmitters (NT) release. Epo therapy in anemic cancer patients is still a controversial issue, because of its possible action as a growth and an angiogenic factor. In our speculative hypothesis Epo could be involved in a "two steps process" that, after a neovascularization phase, leads to its down regulation. Moreover, Epo-activated signaling pathways could be modulated as possible targets to interfere in neoplastic cells cycle. In conclusion, treatment with rHuEpo could change therapeutical perspectives in different pathological conditions, such as central nervous system (CNS) diseases, but further studies are needed to clarify its physiopathological activities in different clinical fields.

Topics: Animals; Brain; Erythropoietin; Humans; Hypoxia; Models, Biological; Neoplasms; Neovascularization, Pathologic; Neurotransmitter Agents; Receptors, Erythropoietin

Cancer patients often receive transfusions when their hemoglobin concentration falls to dangerously low levels due to chemotherapy or due to the disease itself. The availability of recombinant human erythropoietin (rHuEPO) has significantly reduced transfusion frequencies in cancer patients. However, the predictability of transfusions prior to the use of rHuEPO for future transfusions has not been evaluated. Data from five randomized, double-blind, placebo-controlled trials in cancer patients receiving chemotherapy and epoetin alfa were utilized to calculate the relative risk of subsequent transfusions in patients who were pretransfused. A meta-analysis with patient-level data was used to assess predictors of transfusion. Baseline data from an open-label study were used to compare quality-of-life (QOL) parameters between previously transfused and transfusion-naive patients. The mean relative risks (RR) of exposure to additional transfusion for pretransfused patients on placebo or epoetin alfa were 2.14 (95% confidence interval [CI]: 1.73, 2.65) and 2.51 (95% CI: 1.92, 3.27), respectively, compared with nontransfused patients. Data from the meta-analysis of patients on epoetin alfa showed that pretransfusion was the most significant predictor for subsequent transfusions (parameter estimate = -1.2628, p < 0.0001 from Logistic Regression Analysis). While epoetin alfa was similarly effective in reducing transfusion risks for patients with or without pretransfusions (compared with placebo), those who were pretransfused were more than twice as likely to be subsequently transfused, compared with those not pretransfused. QOL was significantly worse for pretransfused patients than for nontransfused patients, as measured by the Functional Assessment of Cancer Therapy -Anemia and the Linear Analogue Scale Assessment QOL instruments. The results suggest that transfusions prior to epoetin alfa therapy increase the risk of future transfusions, and early treatment with epoetin alfa might reduce the risk of subsequent transfusions.

Topics: Adolescent; Adult; Aged; Double-Blind Method; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Recurrence; Risk Factors

Anaemia is considered a common problem in many cancers secondary to the disease itself or related to chemo- and/or radiotherapy. Several clinical trials have advocated the prognostic value of anaemia and hypoxia in the outcome of many cancers. Erythropoietin is recognised as an effective treatment for anaemia, which also improves the quality of life in patients with malignant disease. External radiotherapy plays an important role in the treatment of loco-regional cancer but its efficacy can be compromised by many factors. Tumor hypoxia is considered by many authors as an important factor contributing to radioresistance. We report in this article the radiobiological rationale in favour of combining radiotherapy and erythropoietin, and review relevant clinical papers published in this field.

Topics: Anemia; Clinical Trials as Topic; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Treatment Outcome

The use of recombinant human erythropoietin (r-HuEPO) in cancer patients improves hemoglobin levels and quality of life. This fact, already well known, made oncologists expect a positive outcome in radio and chemotherapy results, as well as in survival. However, new clinical trials show a preliminary evidence of impaired, instead of improved, survival when these agents are prescribed. Erythropoietin (EPO) is becoming a more complex hormone than it was expected. Its non-erythropoietic effects include, among others, angiogenesis and proliferation of certain types of cancer cells. In this work, we review erythropoietin as a natural hormone, as well as the different types of r-HuEPO, focusing on the confusing situation with regard to their use in oncology. We conclude that extreme care must be taken when EPO is prescribed to cancer patients, and we suggest to limit its use to symptomatic anemia, just to achieve moderate hemoglobin levels.

Topics: Anemia; Erythropoietin; Hemoglobins; Humans; Neoplasms; Recombinant Proteins

Anaemia, often associated with chemotherapy, is a common and debilitating disorder in cancer patients. Recombinant human erythropoietin (epoetin alfa) was introduced in the 1990s for the treatment of chemotherapy-related anaemia. Data from randomised, double-blind, placebo-controlled studies and large, non-randomised, community-based studies have demonstrated that either of the FDA-approved dosing schedules of epoetin alfa 150 - 300 U/kg three times weekly or 40,000-60,000 U/week s.c., significantly increases haemoglobin levels, reduces transfusion requirements, and improves quality of life in anaemic cancer patients undergoing chemotherapy or chemoradiation therapy. Guidelines for the effective and safe use of epoetin alfa have been published by major oncology/haematology organisations and are reviewed in this article. Areas of recent and ongoing investigation with epoetin alfa are also covered in this review.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Practice Guidelines as Topic; Recombinant Proteins

Anemia is a common complication of cancer or anticancer therapy, with a significant negative impact on the functional status of patients and their quality of life (QOL). Recombinant human erythropoietin (EPO) was developed in the 1980's and was initially developed for the treatment of anemia associated with chronic renal failure. Subsequently, randomized, placebo-controlled clinical trials in the oncology setting were performed in the early 1990's. These studies demonstrated in cancer patients that EPO could increase the levels of hemoglobin (Hb), decrease the need for red blood cell transfusions, and also suggested that these outcomes were associated with improved QOL metrics as reported by the patients themselves. Based on the results of these studies, EPO was granted regulatory approval to be used for the treatment of anemia in patients with non-myeloid malignancies where anemia was due to the effect of concomitantly administered chemotherapy. To further expand the findings of the registration studies, and to develop more complete QOL data, three similarly designed open-label community-based studies were performed, enrolling a total of approximately 7000 patients. These studies consistently demonstrated in the supportive care of cancer patients receiving chemotherapy that the use of EPO could induce increases in the levels of Hb and that these correlated with patient-reported improvements in QOL metrics. The correlation between an improvement in Hb and QOL has also been confirmed in a larger randomized, placebo-controlled trial. Careful analyses of data from this study also helped support earlier findings that EPO could be effective for patients with varying degrees of anemia, and that increasing and maintaining Hb levels close to the physiologically normal levels resulted in the optimal improvements in QOL. While further investigations of EPO as a mechanism to improve the antineoplastic efficacy of chemoradiotherapy have not yet been positive, the overall experience with this agent remains very favorable after extensive studies and long-term clinical use in oncology.

Topics: Anemia; Erythropoietin; Hemoglobins; Humans; Neoplasms; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

Anemia occurring in patients with renal failure on dialysis has been shown to both increase transfusion requirements and decrease functional status and quality of life. As a result, treatment of these patients with an erythropoietic agent such as epoetin alfa or darbepoetin alfa has become established as an essential part of optimal patient care. Anemia resulting from cancer or chemotherapy is a common problem in oncology, and has been shown similarly to increase transfusion risk and decrease patient reported outcomes. For reasons that are not clear, but may include either frequently encountered slow response or nonresponse and higher doses and hence higher costs, treatment of anemia in oncology has not become a standard treatment for all patients. Erythropoietic agents (epoetin alfa and darbepoetin alfa) have been used to improve anemia-related fatigue and quality of life in cancer patients. Epoetin is administered 1 to 3 times per week whereas darbepoetin, with up to a 3-fold greater half-life, is given once every 1 or 2 weeks. Recent data demonstrate that darbepoetin can be administered as infrequently as every 3 weeks with comparable erythropoietic efficacy. Several studies have been carried out to determine the optimum schedule of dosing to obtain maximum patient benefit. Following treatment with darbepoetin, antibodies to darbepoetin were not detected, no unusual adverse event was seen with darbepoetin, and the mean increase in hemoglobin remained unchanged when the dosing interval was increased from 1 to 2 weeks. The safety and efficacy of darbepoetin was also determined in patients with solid tumors receiving chemotherapy; the lowest clinically effective dose was determined to be 3.0 and 5.0 microg/kg every 2 weeks with a 66 and 84% response, respectively. No additional benefit was seen with higher doses. A multicenter study evaluated the safety and efficacy of darbepoetin administered either weekly, every 3 weeks, or every 4 weeks in anemic patients with cancer who were not receiving chemotherapy or radiotherapy. The results indicated that with weekly dosing, 70% of patients showed an increase in hemoglobin. The dose of 4.5 microg/kg/week resulted in 100% hematopoietic response. In a randomized, active control, pilot trial, front-loading darbepoetin followed by lower doses or less frequent doses also appears to be efficacious and may decrease the time to response. At the present time, darbepoetin improves anemia, reduces requirements for transfus

Topics: Anemia; Clinical Trials, Phase III as Topic; Darbepoetin alfa; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Treatment Outcome

The only combined effort between the American Society of Hematology (ASH) and the American Society of Clinical Oncology (ASCO) in practice guideline development was in studying the use of erythropoietin in chemotherapy-related anemia and in myelodysplasia. This process began with an application to the Agency for Health Care Policy and Research (AHCPR, now called the Agency for Healthcare Research and Quality, or AHRQ) jointly from ASH and ASCO. As part of a competitive review process, the topic was selected by the Agency for funding. Subsequently, as part of the Agency's Evidence-based Practice program, funding to conduct the review was awarded to the Evidence-based Practice Center of the Blue Cross/Blue Shield Technology Evaluation Center, which performed an extensive literature review using principals of evidence-based medicine and with input from representatives of ASH and ASCO. That evidence-based review was then shared with an ASH and ASCO guidelines committee funded by both organizations and made up of members from both organizations. The guideline was developed over a period of 21/2 years, culminating in simultaneous publication in both Blood and The Journal of Clinical Oncology in October 2002. This field is in flux and much of the guideline discussed potential future directions for research. Projected research topics include whether a hemoglobin level of 11g/dl as a clinical trigger point has clinical benefit; whether increasing hemoglobin levels greater than 12g/dL has clinical benefit; what role iron supplementation plays in erythropoietin treated patients; weekly versus more frequent dosing; and cost benefit analyses. Quality of life considerations are important, but the practice guideline committee felt that there was not enough data in this area to view it with the same importance as avoidance of transfusion or rises in hemoglobin value as therapeutic goals for patients being treated with erythropoietin.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Erythropoietin; Hematology; Humans; Neoplasms; Societies, Medical; United States

Epoetin (EPO; erythropoietin) treatment offers an attractive but costly alternative to red blood cell transfusion for managing anemia associated with cancer therapy. The goal of this paper is to review the findings of the 2001 Blue Cross/Blue Shield Association Technology Evaluation Center overview on EPO use in oncology, which served the foundation for the 2002 ASH/ASCO clinical guideline on this subject. The BC/BS review had two major aims: (1) to quantify the effects of EPO on the likelihood of transfusion and on quality of life in patients with cancer treatment-related anemia, and (2) to evaluate whether outcomes are superior when EPO treatment is initiated at higher hemoglobin thresholds. Two independent reviewers followed a prospective protocol for identifying relevant studies published between 1985 and 1998. Outcomes data were combined with the use of a random-effects meta-analysis model. Double-blind, randomized controlled trials that minimized patient exclusions were defined as higher quality for sensitivity analysis; randomized, but unblinded trials and trials with excessive exclusions were included in the meta-analysis, but were defined as lower quality. Twenty-two trials (n=1927) met inclusion criteria, and 12 (n=1390) could be combined for estimation of odds of transfusion. EPO decreased the percentage of patients transfused by 9-45% in adults with mean baseline hemoglobin concentrations of 10g/dL or less (7 trials; n=1080), by 7-47% in those with hemoglobin concentrations greater than 10g/dL, but less than 12g/dL (7 trials; n=431), and by 7-39% in those with hemoglobin concentrations of 12g/dL or higher (5 trials; n=308). In a sensitivity analysis, the combined odds ratio for transfusion in EPO-treated patients as compared with controls was 0.45 (95% confidence interval [CI]=0.33-0.62) in higher quality studies and 0.14 (95% CI=0.06-0.31) in lower quality studies. The number of treated patients needed to prevent one transfusion is 4.4 for all studies, 5.2 for higher quality studies, and 2.6 for lower quality studies. Only studies with mean baseline hemoglobin concentrations of 10g/dL or less reported statistically significant effects of EPO treatment on quality of life; quality-of-life data were insufficient for meta-analysis. No studies addressed the effects of EPO on anemia-related symptoms. The review concluded that EPO reduced the odds of transfusion for cancer patients undergoing therapy. Evidence was insufficient to determine whether i

Topics: Anemia; Blue Cross Blue Shield Insurance Plans; Erythropoietin; Hemoglobins; Humans; Meta-Analysis as Topic; Neoplasms; Outcome Assessment, Health Care; Prospective Studies; Quality of Life

Health care decision-making is affected by the values of patients and providers, available resources, and information substantiating effectiveness (or efficacy) of a particular therapy. A number of factors contribute to our growing need for evidence-based decision-making. Our aging population generally requires greater medical attention in a system with limited resources devoted to health care. Technologic advances have produced an ever-expanding range of expensive treatment options. Patients, and their providers, expect early access to these emerging therapies. Patients also expect care of universally high quality, even as respected authorities suggest there exists a substantial gap between these expectations and the care actually delivered. Evidence based decision-making offers the opportunity to use medical evidence to reduce uncertainty regarding research information and improve the value of health care delivered. Evidence based medicine (EBM) is the 'conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients.' It combines clinical judgment and experience, best available scientific evidence, and patient preferences to improve medical decision-making. Though often incorrectly maligned as cookbook medicine that dismisses any research findings that do not derive from randomized clinical trials, it provides clinicians, health care systems, payers and policymakers with tools to appropriately evaluate the research evidence that substantiates various therapies and integrate that evidence with clinical expertise and patient's values in medical decision-making. The erythropoietic stimulants epoetin and darbepoetin have shown efficacy in improving anemia of chronic renal failure and following chemotherapy for many patients. In some studies these agents have also improved health-related quality of life. Unfortunately, only 60-80% of patients treated with erythropoietic stimulants respond, and like many emerging therapies, they are quite expensive. Likewise, there is substantial variation in their usage, suggesting both inappropriate use and non-usage. Reimbursement coverage decisions for erythropoietic stimulants have been hampered by the lack of high-quality evidence in certain applications. Physicians are increasingly turning to evidence-based medicine resources (guidelines, systematic reviews) to inform their decisions regarding application of new therapies. Evidence-based medicine offers healt

Topics: Anemia; Antineoplastic Agents; Chronic Disease; Erythropoiesis; Erythropoietin; Evidence-Based Medicine; Humans; Neoplasms; Quality of Life

Cancer and cancer therapy-associated anemia may have an impact on tumor response and overall survival. Additionally, anemia represents an important economic factor. Therefore, therapeutic alternatives such as erythropoietin (EPO) and red blood cell transfusions have to be evaluated systematically. The effectiveness of recombinant human EPO to prevent or alleviate anemia in patients with malignant disease was determined. Randomized controlled trials comparing prophylaxis or treatment of anemia with EPO plus red blood cell transfusion (RBCT) or RBCT only in patients with malignant disease undergoing antineoplastic therapy were included. The endpoints needed for RBCT were hematological response (hemoglobin increase of 2g/dL or hematocrit increase of 6%), tumor response, and overall survival. Medical databases (Cochrane Library, MEDLINE, EMBASE) and conference proceedings were searched (1985-2001). Full-text and abstract publications were included as well as unpublished data. Data extraction and quality assessment were done in duplicate. All authors were contacted to obtain missing data. Out of 33 eligible studies, 27 trials with 3,287 randomized patients were included.

Topics: Anemia; Databases, Factual; Decision Trees; Erythrocyte Transfusion; Erythropoietin; Europe; Humans; Meta-Analysis as Topic; Multicenter Studies as Topic; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; United States

Clinical research evidence on outcomes of using epoetin (EPO) to treat or prevent anemia in oncology has recently been systematically synthesized to provide a scientific foundation for developing and implementing clinical practice guidelines. Two groups have distinguished themselves by their meticulous research methods, the Blue Cross and Blue Shield Association Technology Evaluation Center (BCBSA TEC) and the Cochrane Review Group (CRG), and have summarized existing research evidence on the role of EPO in anemia associated with cancer treatment. An ASH/ASCO (American Society of Hematology/American Society of Clinical Oncology) panel has used the BCBSA TEC review to develop practice guidelines on the use of EPO in patients with cancer. The ASH/ASCO guideline panel identified eight important clinical circumstances for which use of EPO in oncology might be considered and used the BCBSA TEC evidence review to formulate evidence-based guidelines that support use of EPO. Both BCBSA TEC and CRG found solid evidence exists to show that EPO improves hemoglobin levels and reduce the risk for transfusion. The ASH/ASCO panel concluded that best empirical evidence exists to support the use of EPO to correct anemia due to chemotherapy if Hgb

Topics: Anemia; Blue Cross Blue Shield Insurance Plans; Erythropoietin; Hematology; Humans; Medical Oncology; Meta-Analysis as Topic; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Research Design; Societies, Medical; United States

Chemotherapy-induced anaemia, with its important consequences on quality of life and social function of cancer patients, can be improved with erythropoietic therapy. Darbepoetin alfa is the first of a novel generation of erythropoietic proteins with a unique molecular structure and a circulating half-life that is threefold longer than that of the previous recombinant human erythropoietin. The efficacy and safety of weekly administration have been confirmed in different Phase II and III randomised trials. In order to optimise the efficacy profile of darbepoetin alfa, extended dosing intervals and front-loading regimens are evaluated, as well the optimal haemoglobin level to initiate therapy. Across all trials, darbepoetin alfa was shown to be a well-tolerated and safe therapy. The possible favourable effect on the outcome of cancer patients needs to be further elucidated.

Topics: Anemia; Antineoplastic Agents; Clinical Trials, Phase III as Topic; Darbepoetin alfa; Drug Administration Schedule; Erythropoietin; Hemoglobins; Humans; Neoplasms; Recombinant Proteins

Anemia associated with cancer and cancer therapy is an important clinical and economic factor in the treatment of malignant diseases.. We conducted a systematic literature review to assess the efficacy of erythropoietin to prevent or treat anemia in cancer patients with regard to red blood cell transfusions, hematologic response, adverse events, and overall survival. We searched the Cochrane Library, Medline, EMBASE, and other databases for relevant articles published from January 1985 to December 2001. We included all randomized controlled trials that compared the use of recombinant human erythropoietin (plus transfusion, if needed) with no erythropoietin treatment (plus transfusion, if needed). Relative risks (RRs) and 95% confidence intervals (CIs) were calculated under a fixed-effects model. Clinical and statistical heterogeneity were examined with sensitivity analyses and meta-regression. Statistical tests for effect estimates were two-sided.. We identified 27 trials involving 3287 adult patients. Patients treated with erythropoietin had a lower relative risk of having a blood transfusion than untreated patients (RR = 0.67, 95% CI = 0.62 to 0.73). Erythropoietin-treated patients with baseline hemoglobin levels lower than 10 g/dL were more likely to have a hematologic response than untreated patients (RR = 3.60, 95% CI = 3.07 to 4.23). The relative risk for thromboembolic complications after erythropoietin treatment was not statistically significantly increased (RR = 1.58, 95% CI = 0.94 to 2.66) compared with that of untreated patients. There is suggestive but inconclusive evidence that erythropoietin may improve overall survival (adjusted data: hazard ratio [HR] = 0.81, 95% CI = 0.67 to 0.99; unadjusted data: HR = 0.84, 95% CI = 0.69 to 1.02).. Erythropoietin treatment may reduce the risk for blood transfusions and improve hematologic response in cancer patients. However, our favorable survival outcome is in contrast to two large (N = 351 and 939) recently published randomized controlled trials in which erythropoietin-treated patients had statistically significantly worse survival than untreated patients. Possible reasons for the disparity with our results include differences in study population and design, higher target hemoglobin levels and higher risk of thromboembolic complications, and concerns that erythropoietin may stimulate tumor growth.

Topics: Anemia; Blood Transfusion; Erythropoietin; Hematinics; Humans; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Survival Analysis; Treatment Outcome

Cancer-related anemia is a cytokine-mediated disorder resulting from complex interactions between tumor cells and the immune system. Overexpression of certain inflammatory cytokines results in shortened survival of red blood cells, suppression of erythroid progenitor cells, impaired iron utilization, and inadequate erythropoietin production. Numerous other factors may also contribute to the development of anemia in cancer patients. The European Cancer Anaemia Survey (ECAS) has provided the most current, comprehensive, prospectively collected data on the incidence and prevalence of anemia among cancer patients, as well as important perspectives on anemia treatment and relationship of hemoglobin and performance status. ECAS enrolled over 15,000 treated and untreated patients with various malignancies from cancer centers in 24 European countries and followed them for up to 6 months. The initial analysis of the ECAS data revealed that 39% of the total cancer patient population was anemic (hemoglobin <12.0 g/dl) at enrollment, although the rate varied according to tumor type, disease status, and cancer treatment status. Of the patients who were not anemic at enrollment and started cancer treatment during the survey, those undergoing chemotherapy--either alone or in combination with radiotherapy--had the highest incidence of anemia (63 and 42%, respectively). Low hemoglobin levels correlated with poor performance status and only 40% of patients who were anemic at some time during the survey received treatment for their anemia. These findings are noteworthy, since a growing body of clinical evidence indicates that the treatment of anemia can significantly improve patients' quality of life and may also improve the clinical outcome.

Topics: Anemia, Hypochromic; Chemotherapy, Adjuvant; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Prevalence; Prospective Studies; Radiotherapy, Adjuvant; Recombinant Proteins

The introduction of recombinant human erythropoietin (rHuEPO) has proven to be a major advance in the therapeutic options available for managing anemia in cancer patients. The results of placebo-controlled clinical trials and large, community-based, open-label studies have confirmed that epoetin alfa, a recombinant human erythropoietin, significantly reduces transfusion requirements, and reliably increases hemoglobin (Hb) levels in anemic (Hb level <12 g/dl) cancer patients undergoing chemotherapy. Increased Hb improves patients' energy level and their ability to perform the activities of daily living, as well as their overall quality of life (QOL). These findings are independent of tumor type and disease status and are comparable in patients receiving nonplatinum- and platinum-based chemotherapeutic regimens. Furthermore, more than a decade of use in clinical trials and by physicians in routine clinical practice has demonstrated that epoetin alfa is safe and well tolerated when used to treat cancer patients with anemia. The availability of epoetin alfa as an alternative to transfusion has changed practices in anemia management; physicians can now treat anemia with the goal of achieving adequate Hb levels to relieve anemia-related fatigue, a major symptom contributing to decreased QOL in cancer patients. Incremental benefit analysis has shown that increasing Hb level from 11 g/dl to 12 g/dl yields the greatest improvement in QOL per 1 g/dl increase in Hb. The demonstrated efficacy of epoetin alfa for increasing Hb levels and improving patient QOL have made this agent a rationale choice for management of cancer-related anemia. Ongoing research will continue to provide new insights into best management of anemia with epoetin alfa in cancer patients.

Topics: Anemia, Hypochromic; Controlled Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Severity of Illness Index

Topics: Anemia; Animals; Cytokines; Erythropoietin; Genetic Therapy; Granulocyte Colony-Stimulating Factor; Humans; Neoplasms; Neutropenia; Receptors, Cytokine; Recombinant Proteins; Signal Transduction

Anaemia effects up to 90% of cancer patients, with more than 60% requiring blood transfusion during or after treatment. With the advent of recombinant human erythropoietins (rHuEPO), an alternative to red blood cell transfusion has become available. So far, three drugs have been approved for the treatment of anaemia in patients with malignancies (epoetin alfa, epoetin beta and darbepoetin alfa). New concepts for the use of erythropoietin in cancer patients include 3- and 4-weekly dosing, as well as loading-dose concepts. Important factors helping to judge the impact of erythropoietin in cancer treatment include pharmacoeconomics and better predictive factors. Lately, the influence of erythropoietin therapy on survival in cancer patients has been discussed very intensively, because conflicting data have emerged. Studies aimed at correcting anaemia in cancer patients had indicated a possible survival advantage of those patients receiving erythropoietin. In contrast, two recent trials aimed at correction of haemoglobin levels beyond anaemia reported a poorer survival of patients receiving erythropoietin. This might grossly be attributed to a higher risk of thrombosis in these patients. The largest systematic review on the use of erythropoietin in cancer patients undergoing treatment indicates a suggestive but not significant survival advantage of erythropoietin-treated patients. In addition, very recent results of a Food and Drug Administration meeting on safety and survival of patients treated with erythropoietin are presented.

Topics: Anemia; Economics, Pharmaceutical; Erythropoietin; Humans; Neoplasms; Prognosis; Recombinant Proteins; Risk Factors; Survival; Thrombosis

Topics: Anemia; Erythrocyte Transfusion; Erythropoietin; Humans; Neoplasms; Practice Guidelines as Topic; Prognosis

Cancer has a negative systemic impact on its host in addition to its local or metastatic effects, and no cancer complication is more ubiquitous than anaemia, a condition for which there is now a specific remedy, the recombinant growth factor erythropoietin. This is not a trivial therapeutic consideration, because cancer-associated anaemia has an adverse influence on survival regardless of tumour type. However, the pharmacological correction of anaemia with recombinant erythropoietin could promote tumour growth, whereas the use of tumour-necrosis factor-alpha (TNFalpha) and TNF-related apoptosis-inducing ligand as antitumour agents could exacerbate anaemia, thereby perpetuating tissue hypoxia and tumour progression.

Topics: Anemia; Carcinogens; Cell Death; Erythropoiesis; Erythropoietin; Humans; Hypoxia; Neoplasms; Recombinant Proteins; Signal Transduction

Treatment with epoetin alfa has repeatedly been shown to improve the quality of life (QoL) of cancer patients with anaemia. We used meta-analytical techniques to synthesise data from all available (published and unpublished) studies of epoetin alfa in cancer patients receiving chemotherapy that used validated QoL instruments. Results from 23 studies were synthesised. These employed the CLAS, FACT, SF-36 and ECOG (WHO) QoL scales. The meta-analysis indicated that treatment with epoetin alfa was associated with a clear and statistically significant improvement in QoL as measured by all subscales of CLAS, all subscales of FACT, and 5 subscales of SF-36. In contrast, control groups experienced no significant change, or, in some cases, a deterioration in QoL. Improvement was related to treatment duration. The generic ECOG (WHO) performance scale indicated that, even though epoetin alfa treatment is associated with clear benefits in terms of QoL, this population of patients receiving chemotherapy for cancer experience a gradual decrease in functional status over time.

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Neoplasms; Quality of Life; Recombinant Proteins

Anemia is common in cancer patients, but its impact is often poorly appreciated. As well as the negative effect of anemia on the quality of life, there is strong evidence that it is associated with poor treatment outcome and reduced survival. The introduction of recombinant human erythropoietin (epoetin) has provided an effective treatment of anemia, without the risk associated with blood transfusion. A recent randomized study of patients with hematological malignancies showed that once-weekly epoetin beta has comparable efficacy at the same overall weekly dose as three-times-weekly treatment. This once-weekly regimen of epoetin beta (NeoRecormon) has been approved by European Regulatory Authorities for patients with lymphoproliferative malignancies and relative erythropoietin deficiency, who are receiving anti-tumor therapy. Darbepoetin alpha (Aranesp) has also recently been approved for once-weekly treatment of anemia in patients with nonmyeloid malignancies receiving chemotherapy. The improved convenience and reduced administration costs associated with a once-weekly treatment may result in more patients receiving the benefits of epoetin therapy.

Topics: Anemia, Hypochromic; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

The management of cancer-related anemia with erythropoietic agents presents many unresolved issues. We reviewed the literature relating to epoetin alfa (Eprex)/Epypo); Ortho Biotech/Janssen-Cilag, High Wycombe, United Kingdom, http://www.orthobiotech.co.uk; Procrit); Ortho Biotech Products, L.P., Bridgewater, NJ, http://www.orthobiotech.com), epoetin beta (NeoRecormon); Hoffman-La Roche, Basel, Switzerland, http://www.roche.com), and darbepoetin alfa (Aranesp); Amgen Inc., Thousand Oaks, CA, http://www.amgen.com) highlighting the results of published clinical trials, safety, and cost-effectiveness. Studies were identified through MEDLINE and the bibliographies of relevant articles. Epoetin alfa, epoetin beta, and darbepoetin alfa have differing pharmacokinetic and pharmacodynamic profiles. They are all effective at reducing transfusion requirements and improving health-related quality-of-life parameters, irrespective of tumor response. A direct comparison between epoetin alfa and darbe poetin alfa is based on limited evidence, which does not allow definitive conclusions about relative efficacy and cost-effectiveness. No predictive factors for response to erythropoietic agents have been validated in prospective trials. The most consistent adverse events are thrombotic and may occur irrespective of an increase in hemoglobin. Recent research indicates that the erythropoietin receptor is expressed in several cancer cell lines, raising the concern of possible stimulation of tumor cell growth by these drugs. Studies on the cost-effectiveness of erythropoietins, particularly compared with transfusion therapy, have been challenging to conduct and analyze and have generated ambiguous results. The use of erythropoietins needs to be optimized in terms of cost-effectiveness, and issues surrounding safety need to be clarified. A stronger methodology for clinical studies and the design of new, randomized, clinical trials is a major priority.

Topics: Anemia; Clinical Trials as Topic; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

The erythropoietic agents have achieved a remarkable degree of success as products for the treatment of anaemia associated with cancer chemotherapy. Three agents, epoetin-alpha, epoetin-beta and darbepoetin-alpha, share this global market and have demonstrated similar efficacy and share similar shortcomings, primarily a lower magnitude of cost/benefit than is the case for the dialysis patient. The continued success of these agents will depend on their ability to address the issue of resistance to therapy in the cancer setting, with the most promising and practical initiatives including cotherapy with parenteral iron, and earlier initiation of therapy. Recently, safety issues have arisen with respect to these agents in the cancer setting, particularly focused on possible promotion of tumour progression. A large body of data suggests that these agents are safe when used in accordance with the package inserts. The data bearing upon these issues will be reviewed and three new agents entering clinical development will be described.

Topics: Animals; Antineoplastic Agents; Clinical Trials as Topic; Drug Industry; Erythropoietin; Humans; Neoplasms

Eighty percent of children with cancer suffer from anemia at the time of diagnosis. The physiopathology of anemia is complex. Although anemia can be life threatening, its consequences on the physical, psychological and social state of the child are often minimized. Blood transfusion is the main treatment of anemia: its efficacy is immediate but shortlasting, and it involves infectious and hemolytic risks. The human recombinant erythropoietin has been used for more than 25-years, and is often prescribed to adults with cancer and anemia. The human recombinant erythropoietin rHuEPO is nowadays used when blood transfusion is contra-indicated because of religious or cultural considerations, although several promising studies have been conducted about rHuEPO and children with cancer since 1996: it might be soon the preferential alternative treatment to anemia in children with cancer.

Topics: Adolescent; Anemia; Blood Transfusion; Child; Child, Preschool; Erythropoietin; Female; Humans; Infant; Leukemia; Lymphoma; Male; Neoplasms; Neuroblastoma; Recombinant Proteins

To review the impact of anemia/tumor hypoxemia on the quality of life and survival in cancer patients, and to assess the problems associated with the correction of this difficulty.. MEDLINE searches were performed to find relevant literature regarding anemia and/or tumor hypoxia in cancer patients. Articles were evaluated in order to assess the epidemiology, adverse patient effects, anemia correction guidelines, and mechanisms of hypoxia-induced cancer cell growth and/or therapeutic resistance. Past and current clinical studies of radiosensitization via tumor oxygenation/hypoxic cell sensitization were reviewed. All clinical studies using multi-variate analysis were analyzed to show whether or not anemia and/or tumor hypoxemia affected tumor control and patient survival. Articles dealing with the correction of anemia via transfusion and/or erythropoietin were reviewed in order to show the impact of the rectification on the quality of life and survival of cancer patients.. Approximately 40-64% of patients presenting for cancer therapy are anemic. The rate of anemia rises with the use of chemotherapy, radiotherapy, and hormonal therapy for prostate cancer. Anemia is associated with reductions both in quality of life and survival. Tumor hypoxemia has been hypothesized to lead to tumor growth and resistance to therapy because it leads to angiogenesis, genetic mutations, resistance to apoptosis, and a resistance to free radicals from chemotherapy and radiotherapy. Nineteen clinical studies of anemia and eight clinical studies of tumor hypoxemia were found that used multi-variate analysis to determine the effect of these conditions on the local control and/or survival of cancer patients. Despite differing definitions of anemia and hypoxemia, all studies have shown a correlation between low hemoglobin levels and/or higher amounts of tumor hypoxia with poorer prognosis. Radiosensitization through improvements in tumor oxygenation/hypoxic cell sensitization has met with limited success via the use of hyperbaric oxygen, electron-affinic radiosensitizers, and mitomycin. Improvements in tumor oxygenation via the use of carbogen and nicotinamide, RSR13, and tirapazamine have shown promising clinical results and are all currently being tested in Phase III trials. The National Comprehensive Cancer Network (NCCN) guidelines recommend transfusion or erythropoietin for symptomatic patients with a hemoglobin of 10-11 g/dl and state that erythropoietin should strongly be considered if hemoglobin falls to less than 10 g/dl. These recommendations were based on studies that revealed an improvement in the quality of life of cancer patients, but not patient survival with anemia correction. Phase III studies evaluating the correction of anemia via erythropoietin have shown mixed results with some studies reporting a decrease in patient survival despite an improvement in hemoglobin levels. Diverse functions of erythropoietin are reviewed, including its potential to inhibit apoptosis via the JAK2/STAT5/BCL-X pathway. Correction of anemia by the use of blood transfusions has also shown a decrement in patient survival, possibly through inflammatory and/or immunosuppressive pathways.. Anemia is a prevalent condition associated with cancer and its therapies. Proper Phase III trials are necessary to find the best way to correct anemia for specific patients. Future studies of erythropoietin must evaluate the possible anti-apoptotic effects by directly assessing the tumor for erythropoietin receptors or the presence of the JAK2/STAT5/BCL-X pathway. Due to the ability of transfusions to cause immunosuppression, most probably through inflammatory pathways, it may be best to study the effects of transfusion with the prolonged use of anti-inflammatory medications.

Topics: Anemia; Blood Transfusion; Erythropoietin; Humans; Hyperbaric Oxygenation; Hypoxia; Neoplasms; Practice Guidelines as Topic; Quality of Life; Radiation Tolerance; Radiation-Sensitizing Agents; Recombinant Proteins

Anaemia, a common problem in patients with cancer, usually leads to severe fatigue, which can dramatically impair patients' quality of life (QOL). Nurses are in the ideal position to assess and monitor cancer patients at risk of anaemia and recommend appropriate supportive care measures to alleviate anaemia-related symptoms. Erythropoiesis-stimulating proteins (ESPs) can increase haemoglobin levels, reduce the need for red blood cell transfusions, and improve QOL in patients with cancer and anaemia. Evidence-based guidelines published by national and international organisations make specific recommendations for the appropriate use of ESPs. Nurses are key members of the multidisciplinary teams that develop practice-specific protocols, which are based on the national guidelines. The practice guidelines should describe protocols to identify patients at risk for anaemia and interventions to correct anaemia, with specific details on the choice of ESP and when such interventions should be initiated and halted. In addition, nurses should also recommend strategies to reduce patient burden, such as patient self-administration with prefilled pens or synchronisation of visits for ESPs with chemotherapy visits, which is made possible with the once-every-3-weeks extended dosing with darbepoetin alfa. The implementation of such practice guidelines should improve the quality of care provided to patients.

Topics: Algorithms; Anemia; Erythropoietin; Hematinics; Humans; Neoplasms; Practice Guidelines as Topic; Recombinant Proteins; Risk Assessment

Anaemia is a common complication of cancer and its treatment. It is also associated with substantial impairment of patient quality of life (QOL). Erythropoietic agents are primary treatment options for cancer-related anaemia (CRA). This review summarises evidence supporting clinical use of the approved erythropoietic agents (epoetin alfa, epoetin beta, darbepoetin alfa). A MEDLINE((R)) search from January 2000 to September 2004 using the search terms "epoetin alfa," "epoetin beta," "darbepoetin alfa," "erythropoietin," and "anaemia" was conducted to identify studies evaluating erythropoietic agents in the treatment of CRA. Recent presentations at professional meetings were also included. Erythropoietic agents increase haemoglobin levels, decrease transfusion requirements, and improve QOL in patients with CRA. However, variations in study design, patient populations, dose titration schedules, and outcome measures among available studies make data comparisons between clinical trials difficult. Head-to-head trials are comparing erythropoietic agents in a randomised setting; other trials are evaluating optimal dosage schedules. Clinically relevant differences among approved erythropoietic agents have not been determined in direct comparative trials; however, epoetin alfa appears to be at least as effective as darbepoetin alfa in treatment of CRA.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Evaluation; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

Anemia is a common and debilitating condition in patients with chronic kidney disease and patients with cancer. Over the last 10 to 15 years, the introduction of erythropoietic therapy has transformed the management of anemia in both these conditions. The first therapeutic agent to be used for the stimulation of erythropoiesis was recombinant human erythropoietin (epoetin). At the turn of this century, darbepoetin alfa, a second-generation erythropoietic agent, became available. Darbepoetin alfa contains two additional N-linked carbohydrate chains, which confer greater metabolic stability in vivo. More recently, a third-generation molecule, Continuous Erythropoietin Receptor Activator (CERA), incorporating a large polymer chain, has been developed. CERA has an elimination half-life in humans that is considerably longer than the half-life of either epoetin or darbepoetin alfa. CERA may also have different receptor binding characteristics and pharmacology from other erythropoietic agents; these characteristics are the subject of ongoing investigation. CERA is currently in phase III clinical trials.

Topics: Adolescent; Adult; Anemia; Animals; Clinical Trials as Topic; Dose-Response Relationship, Drug; Erythropoiesis; Erythropoietin; Half-Life; Humans; Kidney Diseases; Neoplasms; Polyethylene Glycols; Receptors, Erythropoietin; Recombinant Proteins

Anaemia is the most common haematological abnormality encountered by cancer patients. A large European survey of cancer patients (n = 15,367) reported that 67% had anaemia at some point during the survey, and that over 60% of these patients did not receive any treatment for their anaemia. Two other surveys (the FATIGUE surveys) showed that over 75% of cancer patients experienced fatigue at least monthly, with over 30% reporting this symptom on a daily basis. Significantly, patients regarded fatigue as having a greater negative impact on their daily lives than many other cancer- or treatment-related complications, with important emotional and mental consequences including lack of self-motivation, sadness, frustration, and mental exhaustion. Indeed, fatigue was considered so debilitating, 12% of patients felt their quality of life (QoL) was so reduced that they did not wish to continue living. Anaemia is also recognised as an independent predictor of poor prognosis in cancer patients. A systematic review evaluating survival showed a 65% overall increase in the risk of mortality in cancer patients with anaemia. Increasing physicians' awareness of the importance of effectively treating anaemia in cancer patients therefore has the potential to improve prognosis as well as QoL.

Topics: Activities of Daily Living; Anemia; Anemia, Hypochromic; Cost of Illness; Erythropoietin; Fatigue; Humans; Neoplasms; Predictive Value of Tests; Prognosis; Quality of Life; Recombinant Proteins; Risk Assessment; Risk Factors; Survival Analysis; Time Factors; Treatment Outcome

Anaemia has a detrimental impact on quality of life and it is important that this condition is recognised and treated in patients with cancer. Epoetin beta is an effective and well-tolerated treatment of anaemia in patients with a wide range of solid and haematological malignancies. A study in patients with lymphoid malignancies confirms that epoetin beta is equally effective at the same overall weekly dose (30,000 IU weekly) when given once-weekly or three-times weekly. This once-weekly regimen has also proved effective in patients with solid tumours. Once-weekly treatment is more convenient for the patient, potentially improving compliance and is associated with reduced hospital administration costs. The majority of patients with cancer will respond to epoetin therapy with an increase in haemoglobin levels. However, it is of value to identify those patients who are likely to respond, so that cost-effectiveness can be improved. Despite much research into potential predictive factors, follow-up studies are required and clinical judgement remains key to managing the anaemia of cancer. In addition, studies suggest that intravenous iron supplementation can improve response to epoetin therapy in patients with functional iron deficiency. Epoetin beta offers an effective, safe and convenient therapy for the management of anaemia in patients with cancer. Ongoing studies are expected to lead to a greater understanding of the optimal use of epoetins in cancer-related anaemia.

Topics: Anemia, Iron-Deficiency; Antineoplastic Combined Chemotherapy Protocols; Drug Therapy, Combination; Erythropoietin; Hematologic Neoplasms; Humans; Iron Compounds; Multivariate Analysis; Neoplasms; Predictive Value of Tests; Quality of Life; Recombinant Proteins; Treatment Outcome

Anaemia is a condition that frequently occurs in patients with cancer, but a recent survey has cast doubt over whether it is being appropriately treated. These findings are disappointing considering the wealth of data showing the effectiveness of epoetin therapy in patients with cancer. Recently, evidence-based guidelines have been published that aim to provide physicians with the latest information required for optimal management of anaemia in patients with cancer. By increasing physician awareness of the appropriate therapy for anaemia management, more patients may receive the benefits of epoetin therapy.

Topics: Anemia, Hypochromic; Erythropoietin; Evidence-Based Medicine; Humans; Neoplasms; Practice Guidelines as Topic; Practice Patterns, Physicians'; Recombinant Proteins

Recombinant human erythropoietin (epoetin) has become the standard of care in the treatment of anaemia resulting from cancer and its treatment, and chronic kidney disease. The discovery that erythropoietin and its receptor are located in regions outside the erythropoietic system has led to interest in the potential role of epoetin in other tissues, such as the central nervous system. Animal studies have shown that systemically applied epoetin can cross the blood-brain barrier, where it reduces tissue injury associated with stroke, blunt trauma and experimental autoimmune encephalomyelitis. Pilot studies in humans have shown that epoetin treatment given within 8 h of stroke reduces infarct size and results in a significantly better outcome when compared with placebo treatment. Studies also suggest that epoetin has the potential to improve cognitive impairment associated with adjuvant chemotherapy in patients with cancer. Anaemia is a major factor causing tumour hypoxia, a condition that can promote changes within neoplastic cells that further tumour survival and malignant progression and also reduces the effectiveness of several anticancer therapies including radiotherapy and oxygen-dependent cytotoxic agents. Use of epoetin to prevent or correct anaemia has the potential to reduce tumour hypoxia and improve treatment outcome. Several therapeutic studies in anaemic animals with experimental tumours have shown a beneficial effect of epoetin on delaying tumour growth. Furthermore, clinical observations in patients with multiple myeloma and animal studies have suggested that epoetin has an antimyeloma effect, mediated via the immune system through activation of CD8+ T cells. Therefore, the role of epoetin may go well beyond that of increasing haemoglobin levels in anaemic patients, although additional studies are required to confirm these promising results.

Topics: Anemia, Hypochromic; Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Hypoxia; Central Nervous System Diseases; Chemotherapy, Adjuvant; Cognition; Erythropoietin; Humans; Multiple Myeloma; Neoplasms; Pilot Projects; Recombinant Proteins

This review focuses on the pathophysiology, incidence and treatment of anaemia in cancer patients. Causative factors such as different chemotherapy regimens and patient risk factors for the development of anaemia are discussed in order to identify the patient group that is most likely to receive red blood cell transfusions and would thus have the largest benefit from treatment with erythropoietic proteins. The data available with recombinant human erythropoietin alfa, recombinant human erythropoietin beta and darbepoetin alfa are described in more detail and the significant benefit of treating cancer anaemia by these molecules is outlined. Finally, differences in treatment approaches between these erythropoietic proteins are discussed in order to guide treatment decisions specific for the individual patients' situation.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Administration Schedule; Erythropoiesis; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Treatment Outcome

Cancer patients are frequently anemic. Treatment of anemic patients with erythropoiesis-stimulating proteins (ESPs) such as epoetin and darbepoetin is associated with benefits that include a reduced transfusion risk and improved quality of life. The recent reports of two randomized trials in which ESP treatment was associated with a decreased survival raised valid concerns regarding the safety of these agents in oncology practice. Reports of erythropoietin receptors on non-hematologic human tumor cells have increased the level of concern and provided a relatively simple model for the effects of ESPs on tumor progression and resistance to treatment. This article reviews available data, which lead to a number of conclusions: 1) the two trials suggesting a negative impact on survival have serious methodologic issues that may compromise interpretation; 2) when used to treat rather than prevent anemia in cancer patients, ESPs show no significant negative impact on survival outcomes; 3) with the exception of erythroleukemia cell lines, the presence of functional erythropoietin receptors on human tumor cells has not been conclusively shown; and 4) a sound theoretical basis exists, supported by preclinical evidence, that any effect of ESP therapy on tumor outcomes may depend on baseline hemoglobin levels, with different effects when anemic and non-anemic individuals are treated. For the present, it is prudent to withhold ESP therapy unless hemoglobin concentrations fall below 12 g/dL and to titrate treatment to maintain a target of 12 g/dL, with adjustments in therapy to insure that levels do not exceed 13 g/dL.

Topics: Anemia; Animals; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Survival Analysis; Treatment Outcome

Anemia in cancer patients undergoing treatment is common and can cause debilitating symptoms such as fatigue and reduced exercise tolerance. The introduction of recombinant human erythropoietin represents a potential improvement in the treatment of this condition. Clinical studies in patients with solid tumors and nonmyeloid hematologic malignancies have convincingly shown an improvement in mean hemoglobin concentration, a reduction in transfusion requirement along with an improvement in quality of life scores, although an effect on survival is less clear. In myeloid disorders such as myelodysplasia, response to single-agent recombinant human erythropoietin is disappointing but significant synergism with granulocyte colony stimulating factor has been demonstrated and different dosing regimens may also improve response. Unfortunately, a significant proportion of patients remain refractory to treatment. Efforts have been made to identify treatable causes of erythropoietin refractoriness, such as functional iron deficiency, and concomitant intravenous iron supplementation does appear to improve response rates. The search for pretreatment factors that predict response has been largely disappointing, although a promising model for myelodysplasia has been developed that awaits large-scale evaluation. Recombinant human erythropoietin is well tolerated, although there were concerns in the late 1990s due to a rising incidence of pure red cell aplasia in chronic renal failure patients treated with subcutaneous Eprex (Ortho Biologics) in Europe. Since potentially contributory manufacturing processes have been identified and corrected, the incidence of this complication has been falling.

Topics: Anemia; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hematologic Neoplasms; Hemoglobins; Humans; Neoplasms; Prognosis; Quality of Life; Recombinant Proteins

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Practice Guidelines as Topic; Recombinant Proteins

Since its initial indication as hormone-replacement therapy in the anemia of chronic kidney disease, epoetin alfa has become a mainstay of therapy for chemotherapy-related anemia. Clinical studies have shown that epoetin alfa administered once weekly or three times weekly improves hemoglobin levels, decreases transfusion requirements, and improves quality of life independent of tumor response to chemotherapy. Ongoing research is now evaluating ways to improve the response rate to epoetin alfa, the potential benefits of alternative dosing regimens and early treatment intervention, and nonanemia-related indications (e.g., cognitive impairment, asthenia). In addition, scientists are exploring the role of epoetin alfa in preventing apoptosis and ischemic brain injury, as well as its activity in other nonerythroid tissues. Thus, the role of epoetin alfa is likely to expand in the cancer setting in the coming years.

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Recombinant Proteins; Survival Analysis

Anemia is the most common hematological abnormality in cancer patients, unfortunately, it is often under-recognized and under-treated. The pathogenesis of cancer anemia is complex and most of the time multifactorial; involving factors related to the tumor itself or its therapy. While anemia can present in a wide range of symptoms, involving almost every organ, it is believed that it contributes much to cancer-related fatigue, one of the most common symptoms in cancer patients. In addition, there is increasing evidence to suggest that anemia is an independent factor adversely affecting tumor response and patient survival. While blood transfusion was the only option to treat cancer-related anemia, the use of recombinant human erythropoietin (rHuEPO) is becoming the new standard of care, more so with the recent studies demonstrating the feasibility of a single weekly injection. Things are even getting better with the recent approval of a new form of rHuEPO; Darbepoetin, an analogue with a 3-fold longer half-life. In addition to its effect in raising hemoglobin, several well-controlled studies demonstrated decrease in transfusion requirements and better quality of life assessed objectively using standard assessments scales.

Topics: Anemia; Blood Transfusion; Combined Modality Therapy; Comorbidity; Developing Countries; Erythropoietin; Female; Humans; Male; Neoplasms; Prognosis; Recombinant Proteins; Risk Assessment; Saudi Arabia; Severity of Illness Index; Survival Rate; Treatment Outcome

Epoetin beta (NeoRecormon) is a recombinant form of erythropoietin. It increases reticulocyte counts, haemoglobin (Hb) levels and haematocrit. Epoetin beta administered subcutaneously once weekly corrected anaemia and had equivalent efficacy to that of epoetin beta administered three times weekly in patients with haematological malignancies. Subcutaneous epoetin beta reduced transfusion requirements and increased Hb levels versus no treatment in patients with solid tumours and chemotherapy-induced anaemia in nonblind, randomised trials. Anaemia and quality of life were also improved, and blood transfusion requirements were reduced to a significantly greater extent than placebo or no treatment (with supportive blood transfusion) in patients with haematological malignancies. Most patients were receiving chemotherapy. Subcutaneous epoetin beta was well tolerated by patients with cancer; adverse events with the drug occurred with a similar incidence to those with placebo or no treatment (with supportive blood transfusion). Hypertension was relatively uncommon with epoetin beta in clinical trials. Patients with haematological malignancies and a baseline platelet count > or =100 x 10(9)/L, Hb levels of > or =9 g/dL or lower erythropoietin levels have demonstrated better responses to epoetin beta than other patients in clinical trials. However, neither baseline erythropoietin level nor the observed to predicted ratio of erythropoietin levels correlated with the response to epoetin beta in patients with solid tumours and chemotherapy-induced anaemia. A decrease of <1 g/dL or an increase in Hb with epoetin beta during the first chemotherapy cycle indicated a low transfusion need in subsequent cycles in patients with ovarian carcinoma. In general, the efficacy of epoetin beta is not limited by tumour type. Response to the drug occurred irrespective of the nature (platinum- or nonplatinum-based) or presence of chemotherapy treatment in randomised trials.. Epoetin beta has shown efficacy in the management of cancer-related anaemia in patients with haematological malignancies and of chemotherapy-induced anaemia in patients with solid tumours. Once-weekly administration provides added convenience for patients and may be cost saving, although additional research into the potential pharmacoeconomic benefits of this regimen are required. The drug is well tolerated in patients with cancer and is associated with little injection-site pain when administered subcutaneously. Epoetin beta is an important option in the prevention of chemotherapy-induced anaemia, and a valid and valuable alternative to blood transfusion therapy for the treatment of cancer-related or chemotherapy-induced anaemia.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Erythropoietin; Half-Life; Humans; Injections, Subcutaneous; Neoplasms; Quality of Life; Recombinant Proteins

The pharmacoeconomics of erythropoietic therapy for the treatment of anemia is receiving renewed attention due to the current availability of two agents. Epoetin alfa has been the standard of therapy for patients with renal disease and cancer-related anemia for more than a decade. Darbepoetin alfa, an alternative agent, is now approved for anemia resulting from renal disease and cancer chemotherapy.. Although direct comparative trials have not been performed with these agents, information published in the last several years regarding their clinical efficacy, safety, and dosing is sufficient, in most cases, to compare costs. With the disclaimer that any efficacy comparison of competing products using published reports has certain limitations, a cost-minimization approach from a provider's perspective was conducted.. To provide background for the economic evaluation, pharmacokinetic and pharmacodynamic data for these two agents are discussed. Recent clinical trials in the nephrology and oncology therapeutic areas are summarized, highlighting study designs, dosing regimens, patient entry criteria, study endpoints, and published results. Cost data, based on average wholesale prices (AWP) in 2003, are compared and calculated from available clinical data with an emphasis on efficacy.. These evaluations largely conclude that epoetin alfa is the better pharmacoeconomic value of the two currently available erythropoietic agents.

Topics: Anemia; Antineoplastic Agents; Cost-Benefit Analysis; Darbepoetin alfa; Dose-Response Relationship, Drug; Economics, Pharmaceutical; Epoetin Alfa; Erythrocytes; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Neoplasms; Recombinant Proteins; Treatment Outcome

Anaemia is common in people with cancer, and may reduce their quality of life and life expectancy. Blood transfusion can increase haemoglobin levels but is usually reserved for those with moderate anaemia (haemoglobin level below 10 g/dL). A potential alternative is treatment with one of the human recombinant forms of erythropoietin, epoetin alfa (Eprex--Janssen-Cilag) or epoetin beta (NeoRecormon--Roche), or their hyperglycosylated derivative [symbol: see text] darbepoetin alfa (Aranesp--Amgen). These products have improved the management of patients with chronic renal failure who are anaemic. Here we assess the place of the epoetins and darbepoetin alfa in managing anaemia in patients with cancer.

Topics: Anemia; Darbepoetin alfa; Drug Costs; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Survival Analysis; Treatment Outcome

Anemia is common in patients with cancer. This systematic literature review of reports published in 1966 through February 2003 identified the prevalence of anemia in specific cancers and assessed the impact of anemia on survival and quality of life (QOL). Studies about chemotherapy-induced anemia were excluded. Anemia prevalence varied widely; most studies found that between 30% and 90% of patients with cancer had anemia. Prevalence was affected strongly by the definition of anemia: 7% of patients with Hodgkin disease had anemia when the condition was defined as a hemoglobin level <90.0 g/L; as many as 86% of patients had anemia when it was defined as a hemoglobin value <110.0 g/L. Prevalence varied by cancer type and disease stage: 40% of patients with early-stage colon tumors and nearly 80% of patients with advanced disease had anemia. Patients with anemia had poorer survival and local tumor control than did their nonanemic counterparts in 15 of 18 studies. In 8 of 12 studies, patients without anemia (most treated with epoetin) needed fewer transfusions. QOL was positively correlated with hemoglobin levels in 15 of 16 studies. There was no significant difference in treatment toxicity between patients with and without anemia. Tumor hypoxia, which has been associated with resistance to radiation therapy and chemotherapy, may stimulate angiogenesis, leading to poor local control of tumors and increased morbidity and mortality. Treatment of anemia may have a significant impact on patient survival and QOL. However, a standard definition of anemia is needed, as is research about the effect of anemia on cancer progression.

Topics: Activities of Daily Living; Anemia; Blood Transfusion; Comorbidity; Disease Progression; Erythropoietin; Health Status; Hemoglobins; Humans; Incidence; Neoplasm Staging; Neoplasms; Outcome Assessment, Health Care; Patient Satisfaction; Prevalence; Prognosis; Quality of Life; Severity of Illness Index; Survival Analysis

The introduction of recombinant human erythropoietin (RHuEPO) has dramatically changed the therapeutic approach to the anemia of chronic renal failure. Clinical studies have also demonstrated that RHuEPO is effectiveness in various non-uremic conditions, such as anemia associated with onco-hematological disorders, prematurity, HIV infection and to reduce the exposure to allogeneic blood in surgical patients. In this review, we briefly analyze the main clinical applications of RHuEPO, with particular attention to the potential complications deriving from its use.

Topics: Adult; Anemia; Anemia, Neonatal; Blood Transfusion, Autologous; Child; Clinical Trials as Topic; Erythropoietin; Female; HIV Infections; Humans; Infant, Newborn; Infant, Premature, Diseases; Kidney Failure, Chronic; Male; Multicenter Studies as Topic; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins

Anemia is extremely common in patients with cancer. Low hemoglobin levels are associated with diminished quality of life and possibly decreased overall survival. Successful treatment of anemia has undeniable benefits for patients, often yielding dramatic symptomatic improvement that can be very satisfying for clinicians to observe. This review focuses on evolving issues in the management of anemia in patients suffering from cancer. Topics addressed include new evidence-based guidelines concerning the use of epoetin alfa, the evolving role of darbepoetin alfa in cancer-associated anemia, the potential for concomitant iron supplementation to maximize response to erythropoietic agents, the unresolved question of whether erythropoietin use affects survival in cancer patients, new concerns about the risk of thromboembolism in cancer patients with higher hemoglobin levels who are receiving epoetin, and possible immunosuppressive effects of blood product transfusions that may have relevance to neoplasia progression.

Topics: Anemia; Chemotherapy, Adjuvant; Darbepoetin alfa; Drug Therapy, Combination; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Evidence-Based Medicine; Hematinics; Humans; Iron; Neoplasms; Practice Guidelines as Topic; Quality of Life; Radiotherapy, Adjuvant; Recombinant Proteins; Thromboembolism; Treatment Outcome

Anemia is a common condition in patients with cancer. Patients who develop severe anemia are frequently treated with red blood cell transfusions. However, the benefits are transient and associated with a number of risks (such as infection and immunosuppression). An alternative treatment option, recombinant human erythropoietin (rHuEPO) was introduced into the clinical setting more than a decade ago. Today, rHuEPO is increasingly being used to treat anemic patients with cancer. However, despite the well-documented clinical benefits of rHuEPO therapy, it has not been universally adopted as a routine treatment in the oncology setting and there remains an unmet need for an effective and convenient anemia treatment for cancer patients. Longer-acting versions of rHuEPO would avoid the need for frequent injections, increase biological activity and, potentially, the clinical efficacy of rHuEPO. One agent, darbepoetin alfa, is now available for the treatment of anemia in patients with cancer who are receiving chemotherapy, another agent, pegylated-epoetin beta, is in phase II trials, and additional compounds are in early stages of preclinical and clinical development. This review focuses on the available clinical experience with such agents and discusses how dose- and schedule-finding studies are optimizing their clinical use to maximize patient benefits.

Topics: Anemia; Darbepoetin alfa; Erythropoietin; Humans; Neoplasms; Polyethylene Glycols; Recombinant Proteins

Topics: Anemia; Autoimmune Diseases; Cell Hypoxia; Disease-Free Survival; Double-Blind Method; Erythropoietin; Heart Failure; Humans; Kidney; Kidney Diseases; Lymphoma, Non-Hodgkin; Multiple Myeloma; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins

Topics: 2,3-Diphosphoglycerate; Bisphosphoglycerate Mutase; Erythropoiesis; Erythropoietin; Gene Expression Regulation; Hemoglobinopathies; Homeostasis; Humans; Hypoxia; Kidney Diseases; Liver Diseases; Neoplasms; Oxygen; Polycythemia; Polycythemia Vera

Preoperative anemia in a surgical patient predisposes to poor outcomes and allogeneic blood transfusions. As an alternative to transfusions, pharmacologic management of preoperative anemia with recombinant human erythropoietin (rHuEPO) has been well studied in many different types of surgery. rHuEPO, when used alone or in combination with preoperative autologous blood donation before elective surgery, stimulates erythropoiesis and helps to avoid or reduce the need for allogeneic blood transfusions. The clinical evidence on preoperative use of rHuEPO in orthopedic, cardiac, and cancer surgery, as well as in bloodless surgery, is reviewed.

Topics: Anemia; Blood Loss, Surgical; Blood Transfusion; Cardiac Surgical Procedures; Cardiovascular Diseases; Erythropoietin; Humans; Monitoring, Intraoperative; Neoplasms; Premedication; Recombinant Proteins; Treatment Outcome

Topics: Anemia; Clinical Trials as Topic; Erythropoietin; Humans; Neoplasms; Recombinant Proteins; Renal Insufficiency

Hypoxic modification has been the subject of investigations in clinical radiation oncology since the early 60s. To date, this has not yet resulted in a treatment that has been widely accepted. Logistics and technical difficulties limit the routine use of hyperbaric oxygen in radiotherapy. The nitroimidazoles have not gained general acceptance, initially because of their toxicity and later because of doubts about the effectiveness of the newer generation of less toxic drugs. Nevertheless, there is good evidence from these studies that improving clinical outcome by hypoxic modulation is an achievable goal. Newer approaches including combinations of radiotherapy with tirapazamine, erythropoietin, and carbogen and nicotinamide (ARCON) are currently in phase III trial. For these new strategies to be successful, it is important that the proper patient categories are selected. Various methods to assess tumor oxygenation are now becoming available in the clinic. These potential predictive assays must be incorporated and validated in current and future large-scale clinical trials. Modifiers that target other aspects of tumor biology may also have indirect effects on tumor oxygenation. These aspects require further study in preclinical and early clinical settings.

Topics: Antineoplastic Agents; Cell Hypoxia; Clinical Trials, Phase III as Topic; Dose Fractionation, Radiation; Erythropoietin; Humans; Hyperbaric Oxygenation; Neoplasms; Patient Selection; Tirapazamine; Triazines

To determine the occurrence of cancer-related fatigue, the methods used to assess it, and the efficacy of the available treatments, we performed literature searches that identified English-language publications on these topics. Twenty-seven studies were identified in which the quantitative estimation of the occurrence of cancer-related fatigue was an end point. Fifty-six were judged to be relevant to the assessment of fatigue, and 10 randomized controlled clinical trials of treatments of cancer-related fatigue were retrieved. The occurrence of cancer-related fatigue was found to range from 4% to 91%, depending on the population studied and the methods of assessment. Few population-based studies and no longitudinal studies of cancer-related fatigue have been performed. The methods of fatigue assessment were highly variable. Exercise programs show promise to prevent or treat fatigue in some subsets of cancer patients, and the use of epoetin alfa for correction of anemia has been shown to ameliorate fatigue. The number of subjects in the treatment trials was small and their methodologic quality was inconsistent.

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Evidence-Based Medicine; Exercise Therapy; Fatigue; Humans; Neoplasms; Palliative Care; Radiotherapy; Randomized Controlled Trials as Topic; Recombinant Proteins

Anaemia associated with cancer and cancer therapy is an important clinical factor in the treatment of malignant diseases. Therapeutic alternatives are recombinant human erythropoietin (EPO) and red blood cell transfusions.. The aim of this systematic review was to assess the effect of erythropoietin to either prevent or treat anaemia in cancer patients.. We searched the Central Register of Controlled Trials, MEDLINE (01/1985 to 12/2001), EMBASE (01/1985 to 12/2001), other databases and reference lists of articles. We also contacted experts in the field and pharmaceutical companies.. Randomised controlled trials comparing the use of recombinant human erythropoietin (plus transfusion if needed) with red blood cell transfusions alone for the treatment or prevention of anaemia in cancer patients.. Two reviewers independently assessed trial quality and extracted data. All authors from included studies were contacted for additional information.. Twenty seven trials with 3,287 adults were included. Use of erythropoietin significantly reduced the relative risk of red blood cell transfusions (RR 0.67; 95% CI 0.62 to 0.73, 25 trials, n = 3,069). On average participants in the erythropoietin group received one unit of blood less than the control group (WMD -1.00; 95% CI-1.31 to -0.70, 13 trials, n = 2,056). For participants with baseline haemoglobin below 10 g/dL haematological response was observed more often in participants receiving EPO (RR 3.60; 95% CI 3.07 to 4.23, 14 trials, n = 2,347). There was inconclusive evidence whether EPO improves tumour response (fixed effect RR 1.36; 95% CI 1.07 to 1.72, seven trials, n = 1,150; random effects: RR 1.21; 95% CI 0.92 to 1.59) and overall survival (adjusted data: HR 0.81; 95% CI 0.67 to 0.99; unadjusted data: HR 0.84; 95% CI 0.69 to 1.02, 19 trials, n = 2,865). There were no statistically significant adverse effects. Evidence was inconclusive with respect to quality of life and fatigue.. There is consistent evidence that the administration of erythropoietin reduces the risk for blood transfusions and the number of units transfused in cancer patients. For patients with baseline haemoglobin below 10 g/dL there is strong evidence that erythropoietin improves haematological response. There is inconclusive evidence whether erythropoietin improves tumour response and overall survival. Research on side effects is inconclusive.

Topics: Anemia; Erythrocyte Transfusion; Erythropoietin; Humans; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins

The primary function of the glycoprotein hormone erythropoietin (Epo) is to promote red cell production by inhibiting apoptosis of erythrocytic progenitors in hemopoietic tissues. However, functional Epo receptors (Epo-R) have recently been demonstrated in various nonhemopoietic tissues indicating that Epo is a more pleiotropic viability and growth factor. Herein, in vitro and in vivo effects of Epo in the brain and the cardiovascular system are reviewed. In addition, the therapeutic impact of Epo in oncology is considered, including the question of whether Epo might promote tumor growth. Convincing evidence is available that Epo acts as a neurotrophic and neuroprotective factor in the brain. Epo prevents neuronal cells from hypoxia-induced and glutamate-induced cell death. Epo-R is expressed by neurons and glia cells in specific regions of the brain. Epo supports the survival of neurons in the ischemic brain. The neuroprotective potential of Epo has already been confirmed in a clinical trial on patients with acute stroke. With respect to the vasculature, Epo acts on both endothelial and smooth muscle cells. Epo promotes angiogenesis and stimulates the production of endothelin and other vasoactive mediators. In addition, Epo-R is expressed by cardiomyocytes. The role of Epo as a myocardial protectant is at the focus of present research. Epo therapy in tumor patients is practiced primarily to maintain the hemoglobin concentration above the transfusion trigger and to reduce fatigue. In addition, increased tumor oxygenation may improve the efficacy of chemotherapy and radiotherapy. However, tumor cells often express Epo-R. Therefore, careful studies are required to fully exclude that recombinant human Epo (rHuEpo) promotes tumor growth.

Topics: Animals; Cardiovascular System; Erythropoietin; Humans; Neoplasms; Neurons; Neuroprotective Agents

Erythropoietin (EPO) is a hematopoietic growth hormone that regulates survival, proliferation, and differentiation of erythroid progenitor cells. A reduction in tissue oxygenation stimulates EPO production, through a complex feedback mechanism. Patients with cancer-related anemia have an inadequate EPO response that is further impaired by cancer treatments such as chemotherapy. Cancer-related anemia substantially impairs patient functioning and may contribute to poor treatment outcomes. A significant number of studies demonstrates that treatment of anemia in cancer patients using recombinant human EPO (rHuEPO, epoetin alfa) significantly increases haemoglobin (Hb) levels, reduces transfusion requirements, and improves quality of life, particularly by relieving fatigue. Recent data also show that epoetin alfa therapy may improve cognitive function in patients receiving chemotherapy. In addition, the correction of anemia may prolong survival by enhancing tumor oxygenation, thus increasing tumor sensitivity to chemotherapy or radiation. The indicated dose of epoetin alfa is 150-300 IU/kg three times per week, but it is commonly dosed at 40,000-60,000 IU once weekly based on trial data and extensive clinical use. Determining the timing of initiation of epoetin alfa is a clinical judgement; however, data suggest that patient functioning declines and the risk of transfusion increases when the Hb level falls under 12 g/dL.

Topics: Anemia, Hypochromic; Antineoplastic Agents; Cognition; Decision Trees; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Practice Guidelines as Topic; Quality of Life; Recombinant Proteins; Survival Rate; Treatment Outcome

A special form of anemia was observed during the treatment with recombinant human erythropoietin having been applied for more than 15 years. The pure red-cell anemia due to antibodies against erythropoietin was described in chronic renal failure patients. Since oncological patients are also treated with rhuEPO it is interesting to know whether this side effect could be observed in the patients with solid tumors as well. It should be considered in tumorous patients when coexistence of antibodies against rhuEPO with pure red-cell aplasia is demonstrated, and its other causes as immunological disease, thymoma, viral infections (eg. Parvovirus B12, Hepatitis B or C) are excluded. The author collected literature data and found the absence of reports on this side effect in cases of treatment with rhuEPO in cancer patients. The rhuEPO treatment is a safe method for the cure of cancer anemia as antibodies against rhuEPO have not been shown together with PRCA among cancer patients. The possible explanation could be the shorter application time in cancer compared to the chronic renal failure patients. The side effect observed in chronic renal failure patients calls the attention to the precise compliance with the instructions of the manufacturers.

Topics: Antineoplastic Agents; Drug Administration Schedule; Erythropoietin; Humans; Kidney Failure, Chronic; Neoplasms; Recombinant Proteins; Red-Cell Aplasia, Pure

Anemia in patients with cancer causes fatigue, weakness, and impaired concentration, negatively impacting quality of life (QOL). In clinical trials involving patients with cancer who had varied characteristics, it has been shown that epoetin alfa treatment increased hemoglobin levels and improved QOL. A systematic review and metaanalysis of data from those trials was conducted to summarize existing knowledge on the role of epoetin alfa in improving QOL for anemic patients with cancer.. The Cochrane Library and other data bases were searched for published and unpublished, randomized/controlled and single-arm studies that included > or = 20 patients with cancer per arm, epoetin alfa treatment, and QOL assessment by Cancer Linear Assessment Score (CLAS), Functional Assessment of Cancer Therapy (FACT) scale, Eastern Cooperative Oncology Group (ECOG) scale, and/or Medical Outcomes Study Short-Form 36 (SF-36) scale.. Among 11,459 patients from 23 trials, epoetin alfa and control cohorts were indistinguishable (with regard to demographic, clinical, QOL variables) at baseline. Epoetin alfa improved CLAS (20-25%), FACT-Fatigue (17%), and FACT-Anemia (12%) scores (P = 0.05). ECOG scores worsened for control cohorts (P = 0.05); epoetin alfa cohorts remained unchanged. Four of the SF-36 subscales, Physical Function, Role Physical, Vitality, and Social Function, improved with epoetin alfa (P = 0.05). Results adjusted for confounding factors remained consistent.. This metaanalysis confirmed that epoetin alfa improves QOL significantly in patients with cancer, emphasizing the need to manage anemia in this population.

Topics: Anemia; Case-Control Studies; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins

Anaemia is frequently diagnosed in patients with cancer, yet it is difficult to identify a single cause due to its multifactorial aetiology. We conducted a systematic literature review (1996-2003) to produce evidence-based guidelines on the use of erythropoietic proteins in anaemic patients with cancer (see ). Level I evidence exists for a positive impact of erythropoietic proteins on haemoglobin (Hb) levels when administered to patients with chemotherapy-induced anaemia or anaemia of chronic disease, when used to prevent cancer anaemia, in patients undergoing cancer surgery and following allogeneic bone marrow transplantation. The Hb level at which erythropoietic protein therapy should be initiated is difficult to determine as it varied between studies; a large number of Level I studies in patients with chemotherapy-induced anaemia or anaemia of chronic disease enrolled patients with a Hb concentration

Topics: Anemia; Bone Marrow Transplantation; Chronic Disease; Dose-Response Relationship, Drug; Erythropoietin; Hematopoietic Stem Cell Transplantation; Humans; Hypertension; Neoplasms; Quality of Life; Survival Analysis; Thromboembolism

Anemia is a common and potentially debilitating complication of cancer. Darbepoetin alfa (Aranesp, Amgen) has been in routine clinical use for the treatment of chemotherapy-induced anemia since 2002. The extended half-life of darbepoetin alfa permits less frequent and consequently more flexible dosing than other erythropoietic therapies. Data suggest that hemoglobin levels can be effectively and safely increased with darbepoetin alfa in cancer patients who are receiving chemotherapy (patients with treatment-induced anemia), and in those who are not receiving chemotherapy (patients with tumor-induced anemia). This review provides an overview of clinical trial results, particularly those exploring flexible, extended dosing schedules.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Darbepoetin alfa; Delayed-Action Preparations; Erythropoietin; Half-Life; Hemoglobins; Humans; Neoplasms; Quality of Life

The presence of anaemia in patients with cancer is correlated with poor clinical outcome, a reduced tumour response to anticancer therapy and an increased risk of mortality. This observation has led to speculation as to whether treatment of anaemia can enhance survival rates. The majority of studies have suggested that erythropoietic therapy either does not change or improves disease-free and/or overall survival. Only two studies, one in breast cancer and the other in head and neck cancer, both of which used epoetin outside its approved indications, have observed a decrease in survival in epoetin-treated patients compared with controls. Methodological issues and baseline imbalances between groups in prognostic factors for survival that may have favoured placebo treatment have complicated the interpretation of these studies. In contrast, a Cochrane meta-analysis of randomised, controlled trials of epoetin in anaemic patients with cancer that reported survival identified 19 trials up to the end of 2001 with 2,865 patients. This meta-analysis reported a hazard ratio for overall survival of 0.81 (95% CI 0.67-0.99) for adjusted data and a hazard ratio of 0.84 (95% CI 0.69-1.02) for unadjusted data. A recent meta-analysis of nine randomised, controlled trials of epoetin beta (n = 1,413) suggests that use of this therapy is associated with a reduced risk of tumour progression. This meta-analysis also showed that no association existed between the risk of overall mortality or thromboembolic mortality and epoetin beta therapy. These results suggest that treatment of anaemic patients with cancer with epoetin beta is effective and safe.

Topics: Anemia, Hypochromic; Erythropoietin; Hematinics; Humans; Meta-Analysis as Topic; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Rate

The contribution of epoetin beta to the management of cancer-related anaemia over the past decade has been a significant one; increased haemoglobin (Hb) levels, reduced transfusion need and improved patient quality of life (QoL) have been well documented in patients across a wide range of malignancies. In recent years, concerns have been raised over the inconvenience and costs associated with the conventional three-times weekly (tiw) epoetin dosing regimen. As a result, optimising therapy through less frequent dosing (i.e. once weekly) has become a focus of research. The NeoRecormon Once Weekly (NOW) study compared the efficacy and tolerability of epoetin beta 30,000 IU once weekly with a standard 10,000 IU tiw regimen in patients with lymphoproliferative malignancies. The study showed that the once weekly regimen was equally effective as the tiw regimen in increasing Hb levels and reducing transfusion need. Furthermore, the response to once weekly treatment was rapid, with 1 and 2 g/dl increases in Hb level seen at approximately 4 and 8 weeks, respectively. Studies with other erythropoietic agents have also shown the efficacy of the once weekly dosing strategy. Epoetin beta 30,000 IU is now approved for once weekly administration in patients with lymphoproliferative malignancies receiving antitumour therapy, and can be administered using a new 30,000 IU pre-filled syringe. Once weekly administration of epoetin beta offers greater convenience and should reduce administration costs compared with the tiw regimen.

Topics: Anemia, Hypochromic; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Treatment Outcome

Epoetin represents the standard of care in the management of cancer therapy-related anaemia, increasing haemoglobin levels, reducing transfusion need and improving patient quality of life (QoL). Recent research aimed at improving convenience and ease of use has involved all epoetins. In particular, it has confirmed that epoetin beta 30,000 IU once weekly is equally effective as the conventional 10,000 IU three-times weekly regimen in alleviating cancer-related anaemia. Ongoing research aimed at improving still further the effectiveness of epoetins in anaemia treatment is examining the role of concomitant intravenous iron during epoetin beta therapy. With the recent debate over whether epoetin therapy has an effect on treatment outcome and survival, well-designed trials specifically powered to assess survival are required. The BReast cancer-Anaemia and the Value of Erythropoietin (BRAVE) trial is such a study, assessing the impact of epoetin beta on survival and QoL of patients with metastatic breast cancer scheduled to receive anthracycline- and/or taxane-based chemotherapy. The findings of such studies are expected to lead to a greater understanding of the optimal use of epoetins in cancer-related anaemia.

Topics: Anemia, Hypochromic; Clinical Trials as Topic; Cost-Benefit Analysis; Drug Administration Schedule; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Survival Analysis; Treatment Outcome

Anaemia develops in most patients undergoing cancer therapy and invariably induces fatigue, which is a major determinant of QOL. Blood transfusions are reserved for patients with severe anaemia, since blood is a scarce resource and provides a short-lived benefit. Epoetins are recombinant proteins capable of alleviating therapy-related anaemia in 40-60% of cancer patients. The number of patients needed to be treated with epoetins to avoid the transfusion of one unit of blood ranges from 2.6 to 5.2; however, the absolute risk reduction depends on patients' characteristics and dose-escalation. The ratio between acquisition costs of epoetins and blood transfusion requirement is very high; thus, many thousands of dollars needs to be spent on epoetins to save 1 blood unit. Despite this, epoetins have been widely adopted by industrialised countries, where cancer patients are about 2% of the total population. The resulting budget impact of epoetins can be calculated at about 10% of the overall direct cost for cancer care, and it is expected to continue growing by about 20% each year, due to the expanding cancer population and the intensification of cancer therapies. The economic burden of epoetins needs to be weighed against the improvement of patients' QOL and society's willingness to pay for a non-life-saving therapy. All published economic evaluations of epoetins invariably report that this supportive therapy is not cost effective. Society should be made aware of the opportunity cost of treatments and should be allowed to elicit preferences for healthcare interventions and prioritisation criteria. In the near future we expect that a wider range of epoetins, drug patent expiry, a more appropriate patient selection criteria and an improved dosage schedule may help increase the efficiency of cancer-related anaemia management.

Topics: Anemia; Cost-Benefit Analysis; Darbepoetin alfa; Drug Administration Schedule; Drug Costs; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Anemia is a well-known risk factor for decreased local control and survival in patients undergoing curative radiotherapy. There is clear evidence from recent clinical investigations that anemia is an independent risk factor and hemoglobin (Hb) levels during radiotherapy are important (and not pretreatment Hb levels). The most likely explanation for the prognostic impact is the association with tumor hypoxia. An "optimal" Hb range with regard to tumor oxygenation seems to exist, and Hb levels < 11 g/dl and > approximately 15 g/dl impair tumor oxygenation but have (over a broader range) no significant impact on normal tissue oxygenation. There is some evidence from retrospective and prospective studies that the response to radiotherapy and the prognosis, especially in cervical cancers, might be improved if the Hb levels during radiotherapy can be maintained in the optimal range, either by transfusions or by erythropoietin. The effect of any antianemic therapy should be analyzed according to whether or not treatment was successful with regard to achieving optimal Hb levels during irrradiation. Erythropoietin is probably more effective in steadily increasing and stabilizing Hb levels, but bears the risk of overcorrection of Hb levels. The clinical relevance of erythropoietin receptors on tumor cells remains questionable.. Treatment of anemia with the objective of improving local control and survival in radiotherapy patients is probably more difficult and sophisticated than coping with symptoms of anemia or improving quality of life. Nevertheless, the potential of antianemic treatment is high on the basis of experimental and clinical data, and further clinical trials are warranted.

Topics: Anemia; Blood Transfusion; Clinical Trials as Topic; Erythropoietin; Humans; Neoplasms; Practice Guidelines as Topic; Practice Patterns, Physicians'; Radiotherapy

Topics: Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoiesis; Erythropoietin; Humans; Iron; Iron Deficiencies; Neoplasms; Recombinant Proteins

Within the past decade, clinical trials have shown that the presence of anemia can diminish the physical status, functional abilities, and overall quality of life (QOL) of cancer patients and can negatively influence the outcome of their treatment. However, recent preclinical and clinical studies have also shown that increasing hemoglobin levels by administering recombinant human erythropoietin (rHuEPO, epoetin alfa) may ameliorate anemia and, in doing so, improve QOL and possibly result in better treatment outcomes following radiotherapy, chemotherapy, or a combination of these modalities. Several mechanisms by which rHuEPO may improve treatment outcome have been proposed, including correction of tumor hypoxia, increased sensitivity of tumor cells to radiotherapy and chemotherapy, correction of anemia and its associated symptoms (particularly fatigue), and immune-modulated effects of rHuEPO on tumor growth. Improvement of tumor oxygenation by rHuEPO could affect treatment outcome in two ways. First, correction of hypoxia results in the downregulation of hypoxia-inducible factor 1 (HIF-1), a key regulator of cellular adaptive responses to hypoxia (e.g., angiogenesis), including many pathways that are important for tumor growth and metastasis. Interruption of the HIF-1 pathway not only limits growth of the primary tumor but also reduces the potential for the development of more aggressive tumors and metastatic spread, which could ultimately improve treatment outcome. Second, within the tumor, it is the hypoxic cells that are resistant to oxygen-dependent radiotherapy and chemotherapy, and improvement in their oxygenation would increase their sensitivity to the cytotoxic effects of such treatment. Correction of anemia and its associated symptoms, particularly fatigue, can have a beneficial effect on patient QOL, and this in turn may translate into greater tolerance of radiotherapy and chemotherapy, allowing patients to receive full doses and on-schedule dosing, and thus have an increased likelihood of a therapeutic response. Lastly, results of a study using a murine model of multiple myeloma have indicated that rHuEPO may induce an immune-mediated antitumor effect. Therefore, additional research is warranted to further explore the biologic actions of rHuEPO and to determine their relevance to therapeutic outcome.

Topics: Anemia; Animals; Cell Hypoxia; Clinical Trials as Topic; Combined Modality Therapy; Disease Models, Animal; Drug Interactions; Drug Resistance, Neoplasm; Erythropoietin; Fatigue; Humans; Mice; Multiple Myeloma; Neoplasms; Quality of Life; Radiation Tolerance; Recombinant Proteins; T-Lymphocytes; Treatment Outcome

Increasingly, anemia is being recognized as a negative prognostic and predictive factor for patients undergoing chemotherapy, radiation therapy, or a combination of these treatment modalities. The results of clinical studies have shown correlations between anemia and shorter survival times in patients with a wide variety of solid tumors and hematologic malignancies, including lung, ovarian, breast, and head/neck cancers, non-Hodgkin's lymphoma, Hodgkin's disease, Waldenstrom's macroglobulinemia, and chronic lymphocytic leukemia. Also, anemia has been shown to predict treatment response in patients with ovarian, cervical, and urothelial cancers, mantle cell lymphoma, and chronic lymphocytic leukemia, as well as refractory/relapsed acute myelogenous leukemia. Based on the presumed causal relationship between anemia and poor patient outcome, several studies have examined the influence of epoetin alfa (a recombinant human erythropoietin) on outcomes in anemic patients undergoing cancer treatment. The results of these studies have been encouraging, with indications of greater locoregional tumor control and higher response rates in epoetin alfa-treated patients. Additionally, epoetin alfa therapy, by correcting anemia, has been shown to improve a patient's energy level, ability to perform daily activities, and overall quality of life (QOL). Such effects not only enhance a patient's general well-being, but may also increase their tolerance of, and willingness to undergo, full courses of their cancer therapy in a timely manner. These findings support the use of epoetin alfa to achieve gains in QOL and cancer treatment outcomes in anemic cancer patients and suggest that additional studies be conducted to further investigate the potential benefits of this agent in regard to improved outcomes.

Topics: Activities of Daily Living; Anemia; Erythropoietin; Fatigue; Hemoglobins; Humans; Neoplasms; Prognosis; Quality of Life; Recombinant Proteins; Treatment Outcome

Severe, debilitating fatigue is common in cancer patients. For many, it is the symptom that interferes most with normal routines. Virtually every modality used to treat cancer may cause fatigue, as can complications of the disease such as sleep disturbances, infections, malnutrition, hypothyroidism, and anemia. There is a significant overlap between depression and fatigue in many patients. Given the high prevalence of cancer-related fatigue, frequent assessment of patients is essential. The evaluation should include an attempt to identify reversible causes of fatigue, and screening for depression. However, many cancer patients suffer from fatigue even in the absence of any identifiable, reversible cause. For these patients, consideration can be given to suitable exercise programs, educational support and counseling, and energy conservation strategies. A trial of a stimulant medication is also reasonable. Given the heterogeneity of patients, individualized approaches are needed. For anemic patients undergoing chemotherapy, erythropoietic agents can increase hemoglobin levels. The impact of these drugs on fatigue and quality of life is uncertain. Recent reports of increased mortality and thrombotic events in cancer patients treated with epoetin require further investigation.

Topics: Antidepressive Agents; Antipsychotic Agents; Combined Modality Therapy; Counseling; Depression; Diagnosis, Differential; Drug Administration Schedule; Erythropoietin; Exercise; Fatigue; Humans; Neoplasms; Palliative Care; Randomized Controlled Trials as Topic; Self-Help Groups; Severity of Illness Index; Terminally Ill

Topics: Animals; Blood Platelets; Cell Differentiation; Cell Division; Central Nervous System; Erythropoietin; Humans; Kidney Failure, Chronic; Neoplasms; Neuroprotective Agents; Recombinant Proteins

Anaemia is frequent in cancer and may increase tumour hypoxia that stimulates angiogenesis. However, erythropoietin is a hypoxia-inducible stimulator of erythropoiesis which seems to improve quality of life in cancer patients. Two recent phase III randomized studies showed negative results using erythropoietin in head and neck cancer patients and in metastatic breast cancer patients with impaired specific survival. In vitro and in vivo experiments have provided erythropoietin-receptor expression in endothelial cancer cells including malignant tumours of the breast, prostate, cervix, lung, head and neck, ovary, melanoma, stomach, gut, kidney etc. Biologic effect of erythropoietin and its receptor linkage induces proliferation of human breast cancer and angiogenesis and may limit anti-tumour effect of cancer treatment, in part, by tumour vascularization improvement. In addition, the use of exogenous erythropoietin could be able to favour tumour progression by improving tumour oxygenation and nutriment supply. If erythropoietin receptor were functional in human cancer, the assessment of erythropoietin receptor expression on tumour cell may help to select patients benefiting from exogenous erythropoietin. However, the relationship between erythropoietin receptor expression, tumour growth and exogenous erythropoietin, requires more studies. The results of recent clinical trials suggest that using erythropoietin should be avoided in non-anemic patients and discussed in patients receiving curative therapy.

Topics: Anemia; Animals; Clinical Trials, Phase III as Topic; Erythropoietin; Female; Humans; Male; Mice; Neoplasms; Neoplasms, Experimental; Neovascularization, Pathologic; Prognosis; Rats; Receptors, Erythropoietin

Anemia complicates the course of disease in about 50% of patients with cancer, and negatively affects their quality of life. A correct approach to therapy should consider all the possible causes and patients need to be treated accordingly. The observation that erythropoietin production is often blunted offers new treatment possibilities. Fifty to 70% of anemic patients respond to rHuEpo, given in a three times or once-a-week schedule. The novel hyperglycosylated protein darbepoetin permits longer intervals between administrations, thanks to its longer half-life, and a once per cycle or once-a-month schedule is a reasonable target. Correction of anemia improves the quality of life, and it has been hypothesized that improvement of cognitive function may derive from a direct effect of Epo on CNS cells. Although anemia is an adverse prognostic factor in cancer, results of recent clinical trials have raised the question whether rHuEpo may favor neoplastic cell proliferation. Results are conflicting at the moment, and further studies are required before arriving at a conclusion. Data available so far do not indicate any negative effect of darbepoetin on the outcome of cancer disease, nor has the production of anti-darbepoetin antibodies or PRCA been reported, a complication observed in less than 200 patients with anemia due to renal insufficiency and treated with rHuEpo alpha.

Topics: Anemia, Iron-Deficiency; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Humans; Male; Neoplasms; Prognosis; Quality of Life; Recombinant Proteins; Severity of Illness Index; Treatment Outcome

Recombinant human eythropoietin (rh-epo) is a well established treatment for many kinds of anemia including the anemia of cancer with or without myelosuppressive chemotherapy. This review considers the effects of rh-epo in humans, tumour-bearing and healthy experimental animals treated with cisplatin with or without rh-epo, and proposes that the ability of rh-epo to improve the quality of life in cancer patients may also be due to interference with the prostaglandin pathways.

Topics: Anemia; Animals; Antineoplastic Agents; Cisplatin; Erythropoietin; Humans; Models, Biological; Neoplasms; Prostaglandins; Quality of Life; Rats; Recombinant Proteins

Anemia occurs frequently in patients with cancer and is associated with impaired health-related quality of life (HRQOL). Treatment of anemia results in significant improvements in energy, activity and overall HRQOL, particularly among patients with mild-to-moderate anemia. Importantly, studies have indicated that anemia may have a negative impact on the success of radiotherapy, reducing survival and locoregional control. Recent preclinical and preliminary clinical data have also suggested that anemia may be associated with poorer outcomes following chemotherapy or surgery.. Data for review were identified and selected from searches of the literature published from January 1990 through to October 2002 using Medline, and searches of proceedings from key international oncology and hematology meetings.. A wealth of data indicate that treatment of anemia improves HRQOL in patients with cancer. Prospective studies exploring survival and/or treatment outcomes in anemic cancer patients are currently in their early stages, preventing any firm conclusions from being drawn, although they do indicate a benefit in treating anemia.. Recent studies support the use of erythropoietic agents in anemic cancer patients as a means of raising their hemoglobin levels and consequently improving their HRQOL. Randomized, controlled trials are needed to determine whether treating anemia with erythropoietic agents will improve other outcomes following therapy.

Topics: Anemia; Darbepoetin alfa; Erythropoietin; Fatigue; Health Status; Humans; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Survival; Treatment Outcome

Significant progress has been made in the prevention and management of many symptoms associated with cancer and its therapy. Anemia in cancer may be secondary to blood loss, displacement of normal bone marrow cells by malignant cells, myelotoxic therapy, or the tumor itself. Practitioners may not always adequately assess anemia unless it represents a source of significant symptoms or patient distress. Risk factors include platinum-based treatment regimens, specific tumor types, and low baseline hemoglobin levels. Anemia may have an impact on patient performance status, quality of life, clinical symptoms, and possibly therapeutic efficacy and survival. Treatment interventions, directed toward the underlying etiology of the anemia, involve iron supplementation, blood transfusion, and administration of recombinant human erythropoietin. Future advances may include new tools to assess physical or functional symptoms and predict therapeutic response more accurately, and more cost-effective, convenient agents to prevent or treat anemia in cancer. Novel approaches that may add to the armamentarium of strategies designed to address anemia in patients with cancer currently are being developed.

Topics: Anemia; Blood Transfusion; Erythropoietin; Hematinics; Humans; Neoplasms; Nurse's Role; Nursing Assessment; Oncology Nursing; Prevalence; Quality of Life; Risk Factors; Treatment Outcome

Although it is well established that the growth of solid tumors requires vigorous neovascularization, it has been assumed that leukemias and other hematological malignancies do not depend on angiogenesis. However, the role of angiogenesis in growth and survival of neoplastic cells of the hematopoietic system has recently been recognized, and provides a rationale for novel therapeutic approaches to hematological malignancy. This review summarizes the literature concerning the relationship between angiogenesis and disease progression of several hematological malignancies. It is becoming increasingly evident that agents that interfere with blood vessel formation also block tumor progression, and, accordingly, antiangiogenic therapy has gained much interest as a potential adjunct to conventional therapy of many hematological malignancies. Recent successful applications of antiangiogenic agents that interfere or block the progression of hematological malignancies are evaluated in light of recent demonstrations of potent angiogenic activity of several hematopoietic growth factors. A novel finding regarding the role of angiogenesis in hematological malignancies, which accounts for many clinical observations as well as the apparent independence of these tumors on marrow vascularity, is presented. The information presented in this review will facilitate the design of future clinical trials using antiangiogenic agents for the treatment of hematological malignancies and will provide a basis for the design of experiments undertaken to define the mechanisms involved, mechanisms that may shed new light on the pathology of hematological malignancies.

Topics: Angiogenesis Inhibitors; Animals; Chick Embryo; Clinical Trials as Topic; Disease Progression; Erythropoietin; Humans; Leukemia; Lymphoma; Matrix Metalloproteinases; Neoplasms; Neovascularization, Pathologic; Recombinant Proteins

Chemotherapy-induced anaemia has important consequences on the quality of life and social function of cancer patients. The finding of erythropoietin (EPO) deficiency in these patients led to the therapeutic development of erythropoietic proteins. Darbepoetin alfa (Aranesp), Amgen Inc, Thousand Oaks, California), a new erythropoietic growth factor, has eight more sialic acids than epoetin alfa. The increased sialic acid content confers a three-fold longer half-life and allows the drug to be administered less frequently than epoetin alfa. Darbepoetin alfa affects the same early haematopoietic cells as epoetin alfa and the endogenous hormone EPO. Preclinical pharmacokinetic studies suggest that the intrinsic pharmacological properties of darbepoetin alfa are comparable to those of epoetin alfa, but that the increased sialic acid content allows for less-frequent administration with superior performance. Darbepoetin alfa has been shown to have safe clinical efficacy in a variety of tumour settings and with several types of chemotherapy.

Topics: Anemia; Animals; Antineoplastic Agents; Darbepoetin alfa; Drug Administration Schedule; Erythropoietin; Humans; Neoplasms

For previously untreated patients receiving most chemotherapy regimens, primary prophylactic administration of granulocyte colony-stimulating factor (G-CSF) cannot be recommended. Secondary prophylactic G-CSF administration can lessen incidence of febrile neutropenia (FN) in subsequent cycles of chemotherapy in patients with a prior episode of FN. Physicians should consider chemotherapy dose reduction after neutropenic fever or severe or prolonged neutropenia after the previous cycle of treatment. Intervention with G-CSF in afebrile neutropenic patients is not recommended. For the majority of patients with FN, the available data do not clearly support the routine initiation of G-CSF as an adjunct to antibiotic therapy. However, certain FN patients may have prognostic factors that are predictive of clinical deterioration, such as pneumonia, hypotension, multiorgan dysfunction (sepsis syndrome), or fungal infection. The therapeutic use of G-CSF together with antibiotics may be reasonable in such high-risk patients. Empirical antifungal therapy is effective, especially for patients with neutropenia who were treated for seven days with empirical antibiotic therapy but remained febrile, or became afebrile but then had recurrent fever. The patient's overall clinical status and laboratory parameters are both considered when deciding to transfuse a patient. Epoetin may be available for use in the future as a treatment option for patients with chemotherapy-associated anemia with a hemoglobin level less than 10 g/dl. Giving prophylactic platelets at a threshold of 10,000/microliter compared with 20,000/microliter can decrease the total utilization of platelets with only a small adverse effect on bleeding, and no statistically significant effect on morbidity.

Topics: Anemia; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Erythropoietin; Fever; Granulocyte Colony-Stimulating Factor; Guidelines as Topic; Humans; Neoplasms; Neutropenia; Platelet Transfusion; Recombinant Proteins; Risk

Thirty per cent of cancer patients suffer from anemia before any treatment. This anemia is caused by haematopoiesis troubles related to cytokines production and by endogenous erythropoietin deficiency. Clinically, its symptoms, including fatigue, spoils patients'quality of life. Known as a prognostic factor for several cancers, anemia also lowers radiotherapy or chemotherapy efficiency by tumor hypoxia. Recombinant EPO restores normal haemoglobin level, quality of life and treatment efficiency.

Topics: Anemia, Aplastic; Cell Hypoxia; Erythropoietin; Fatigue; Female; Humans; Neoplasms; Oxygen Consumption; Quality of Life; Uterine Cervical Neoplasms

Anemia is a real and frequent complication during the management of cancer patients. It is define as a decrease of the erythrocyte mass. The hemoglobin rate (which was an estimation of this erythrocyte mass) is the most often using criteria. The inferior threshold change with the sex and the age of the patients. This is 13 g/dl for the men and 11.5 g/dl for the women. This rate would be however decrease without any other associated pathology. This anemia is due to nutritional context of the patients and complications of the cancer pathology or his management (treatments). Anemia due to the chemotherapy toxicity is a real problem to investigate, to quantify, to prevent or to treat. The chemotherapy toxicity worsened previous anemia (inflammatory ethiology) which physiopathology is multifactoriel and depends on drugs, patients' characteristics, and sort of cancer. Anemia is also a therapeutic problem. Whatever is the severity of the anemia, impact on the quality of life with physical and social consequences is clear. In addition, anemia could relieve of specific treatment such as blood transfusion or preventive treatment with recombinant erythropoietin.

Topics: Age Factors; Anemia; Antineoplastic Agents; Erythrocyte Transfusion; Erythropoietin; Female; Hemoglobins; Humans; Male; Neoplasms; Quality of Life; Recombinant Proteins; Severity of Illness Index; Sex Factors

The role of oxygen as an enhancer of the biological effect of ionising radiation is crucial for radiotherapy. Most of the solid tumours have an inadequate vasculature (neo-angiogenesis) leading to hypoxic areas, favoured by anaemia. Many clinical approaches have been used to overcome this problem with oxygen breathing, radiosensitizing drugs or anaemia correction. All these parameters will be developed together with the methods available for measuring tumour oxygenation and the biological consequences of anaemia and hypoxia on tumour physiology.

Topics: Anemia; Blood Transfusion; Cell Hypoxia; Erythropoietin; Hemoglobin A; Humans; Neoplasms; Oxygen; Oxygen Consumption; Partial Pressure; Radiation-Sensitizing Agents

Anemia is a reduction in the oxygen-carrying capacity of red blood cells that results in a variety of symptoms, including dyspnea, headaches, light-headedness, and fatigue. Although anemia has been associated with reduced health-related quality of life (HRQoL), its treatment has not yet been consistently shown to improve HRQoL.. This systematic review of the literature was conducted to determine whether the treatment of anemia improves HRQoL domains, regardless of the type of underlying disease.. Data for this review were drawn from the clinical trial databases from 2 previous systematic literature reviews of erythropoiesis-stimulating protein treatment for renal insufficiency- and cancer-related anemia, both spanning the period January 1, 1980, through December 31, 2001. MEDLINE, Cancerlit, and Current Contents/Clinical Medicine were searched using the combined terms erythropoietin, kidney failure, neoplasms, and anemia. The reference lists of all identified articles were searched manually for additional relevant papers. The review included prospective studies that reported both HRQoL and hematocrit (Hct) in patients with cancer or renal insufficiency who received treatment for anemia with an erythropoiesis-stimulating protein. HRQoL was categorized by domain (overall, energy/fatigue, physical, activity); changes in HRQoL domains were expressed as effect sizes and meta-analyzed, as were correlation coefficients. The effects on HRQoL of dropout rate, study duration, baseline Hct, and change in Hct were examined in meta-regression analyses.. Sixteen studies each were identified in patients with renal insufficiency (N = 2253) and patients with cancer (N = 10,695). The treated groups included 11,710 patients, and the control groups included 1238 patients. The baseline Hct in all treated groups averaged 26.0%: 28.3% in the group with cancer and 24.4% in the group with renal insufficiency. The mean improvement in Hct from baseline to the end of treatment was 8.3% (range, 1.0%-16.5%) in treated patients and 1.0% (range, 0.0%-3.3%) in controls. The Hct changes were similar in treated patients with cancer and treated patients with renal insufficiency, as was the HRQoL effect size (0.43). Dropout rate and study duration were not significant predictors of HRQoL changes, but change in Hct was a significant predictor in both conditions. Meta-analysis of the correlation coefficients, adjusting for HRQoL domains, showed a consistent and significant positive correlation between change in Hct and change in HRQoL (P < 0.001).. The consistency in both direction and magnitude of effect across many studies and thousands of patients supports the hypothesis that treatment of anemia with erythropoiesis-stimulating protein improves selected HRQoL domains in patients with renal insufficiency- or cancer-related anemia.

Topics: Anemia; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematocrit; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Renal Insufficiency; Treatment Outcome

The introduction of recombinant human erythropoietin (RHuEPO) has revolutionised the treatment of patients with anaemia of chronic renal disease. Clinical studies have demonstrated that RHuEPO is also useful in various non-uraemic conditions including haematological and oncological disorders, prematurity, HIV infection, and perioperative therapies. Besides highlighting both the historical and functional aspects of RHuEPO, this review discusses the applications of RHuEPO in clinical practice and the potential problems of RHuEPO treatment.

Topics: Anemia; Blood Transfusion; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Kidney Transplantation; Neoplasms; Postoperative Complications; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Darbepoetin alfa is a novel erythropoiesis-stimulating protein developed for the treatment of anemia. It is a hyperglycosylated analog of recombinant human erythropoietin with the same mechanism of action as erythropoietin, but with a three-fold longer terminal half-life after intravenous administration than recombinant human erythropoietin and the native hormone both in animal models and in humans. Clinical studies in patients with chronic renal failure either receiving or not receiving dialysis have shown that darbepoetin alfa is equivalent to recombinant human erythropoietin in terms of increases in hemoglobin concentration, percentage of patients achieving target hemoglobin concentration and average time to reach target hemoglobin concentration, although darbepoetin alfa is administered less frequently (once weekly or every other week). Clinical trials in cancer patients either receiving or not receiving chemotherapy have demonstrated that darbepoetin alfa is safe and effective in alleviating anemia at dose intervals of once every 1, 2 or 3 weeks, and results suggest that it may achieve greater and more rapid responses than recombinant human erythropoietin in cancer patients. Furthermore, an improvement in health-related quality of life has been observed in association with anemia correction using darbepoetin alfa therapy in these patients. Darbepoetin alfa has been approved for intravenous and subcutaneous administration by the European Commission and the FDA for the treatment of anemia in patients with chronic renal failure. Additionally, this product was recently approved by the FDA for the treatment of anemia in patients with nonmyeloid malignancies where anemia is due to the effect of concomitantly administered chemotherapy. The recommended starting dose in chronic renal failure patients is 0.45 microg/kg once weekly for both intravenous and subcutaneous administration, with subsequent titration based on the hemoglobin concentration. In cancer patients, the recommended starting dose is 2.25 microg/kg once weekly by subcutaneous injection and subsequent titration. The adverse event profile of darbepoetin alfa is similar to that of recombinant human erythropoietin in both settings. There are no reports of antibody formation associated with darbepoetin alfa in chronic renal failure patients, and three cases of antibody formation, with neutralizing activity in one of the cases, have been reported in cancer patients. However, no cases of antibody-medi

Topics: Anemia; Animals; Clinical Trials as Topic; Darbepoetin alfa; Erythropoiesis; Erythropoietin; Humans; Kidney Failure, Chronic; Neoplasms; Stimulation, Chemical; Treatment Outcome

Erythropoietin (Epo) is produced by the fetal liver and adult kidney and is an essential stimulator of erythropoiesis. It has, however, been shown to modulate host cellular signal transduction pathway to perform many other functions. New sites of Epo production have been found, such as the female reproductive organs and central nervous system. This review summarizes the involvement of Epo in the regulation of angiogenesis in both normal and pathological conditions.

Topics: Angiogenesis Inducing Agents; Brain; Erythropoietin; Female; Genitalia, Female; Humans; Neoplasms; Neovascularization, Pathologic; Neovascularization, Physiologic

The National Health Service (NHS) Cancer Plan published in 2000 has a short-term focus on the most pressing problems of improving survival rates and replacing equipment. It also mentioned as a target 'improved quality of life for those affected by cancer'. Continuity of care for longer-term care programmes was seen predominantly in terms of palliative care. Recent National Institute for Clinical Excellence (NICE) reports may have reinforced this approach by focussing on the clinical and cost effectiveness of chemotherapy for late-stage cancer. The impact on local decision-makers has been that drug funds have been prioritised for use on survival-enhancing interventions, with few resources left for short and longer-term supportive care targeted primarily on improving quality of life. Within supportive care, resources are particularly limited for funding treatments such as erythropoietin for the management of cancer-related anaemia, a common and very debilitating side-effect of intensive therapy. The need for a re-focusing on supportive care is associated with cancer becoming, in many instances, a longer-term illness. The prevalence of cancer is rising markedly due to increased survival rates. However, this creates a new challenge of reducing disability and improving quality of life. In surveys, patients have rated fatigue associated with anaemia as one of the most debilitating effects of their cancer and its treatment with chemotherapy. This paper reviews the evidence demonstrating the quality of life benefits of erythropoietin, and then considers the policy constraints that have limited the adoption of this treatment within the NHS. Through co-ordinated planning there are opportunities for cancer networks and primary care trusts (PCTs) working with cancer centres to develop more support in ways which are feasible and fundable. The case is argued that PCTs and cancer networks, in implementing the Cancer Plan locally, need to integrate short- and longer-term supportive care into their cancer service development plans, and recognise the importance of anaemia management as an integral part of this. Lessons can be learnt from UK renal services where anaemia management with erythropoietin is standard practice.

Topics: Anemia; Blood Transfusion; Community Networks; Erythropoietin; Fatigue; Humans; Neoplasms; Practice Guidelines as Topic; Primary Health Care; Quality of Life; Recombinant Proteins; State Medicine; United Kingdom

Treatment with recombinant human erythropoietin (epoetin alfa) has been shown to enhance quality of life and cognitive function. The mechanism of action for these changes appears to involve more than the alleviation of cancer treatment-induced anemia. Rather, there is increasing evidence that epoetin alfa treatment may modulate a series of cascading events that involve hypoxia-induced activation of vascular endothelial growth factor and an induction in the expression of vascular endothelial growth factor receptors via a hypoxia-inducible factor-1-mediated transcription among several other hypoxia-related events. The use of epoetin alfa to interfere with this hypoxia-induced cascade could provide significant benefits for cancer patients by enhancing survival through a direct modulation of tumor angiogenesis and effectiveness of cancer therapy. The enhanced quality of life seen with erythropoietin treatment may also involve a modulation of hypoxia-induced decrement in cognitive functioning. It appears that epoetin alfa is a useful addition to the treatment of breast cancer.

Topics: Angiogenesis Inhibitors; Apoptosis; Breast Neoplasms; Cell Hypoxia; Central Nervous System; Cognition; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Neovascularization, Pathologic; Recombinant Proteins

Anaemia in cancer patients is multifactorial. Anaemia of chronic disease due to the effects of cancer, as well as side effects of cancer treatment, are important factors. The impact of anaemia on the quality of life and social function of cancer patients has recently become more acknowledged. The traditional treatment for chemotherapy-induced anaemia (CIA) has been the use of red blood cell transfusions, with only short-lived effects and all their inherent risks. The finding of deficiency in erythropoietin, the endogenous hormone responsible for the production and maintenance of red blood cells in these patients, was the basis for the therapeutic development of erythropoietic proteins. With the introduction of epoetins (recombinant forms of human erythropoietin) in oncology and more recently, the novel long-acting darbepoetin alpha, physicians gained new pharmacotherapeutic approaches to treat CIA. Several forms of erythropoietic proteins are available in various regions of the world. Their characteristics, clinical evidence for use, guidelines for clinical administration and their safety are described in this review.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

As the population ages, a dramatic increase in the number of cases of cancer is expected and the need for supportive-care agents, those used to ameliorate some of the side effects of cancer or its treatment, becomes more urgent. At present, supportive-care products are available and new agents are being developed with novel mechanisms of action or modifications of existing agents that improve performance. Because of the urgent need for such products, efficient development is required to deliver useful products to patients as rapidly as possible. This chapter uses actual examples to illustrate the stages of drug development, phase I through phase 3.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Darbepoetin alfa; Drug Approval; Drug Design; Drug Evaluation; Erythropoietin; Fibroblast Growth Factor 7; Fibroblast Growth Factors; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Neoplasms; Neutropenia; Palliative Care; Polyethylene Glycols; Quality of Life; Recombinant Proteins; Stomatitis; United States

Recombinant human erythropoietin (epoetin alfa) has proven beneficial for the treatment of various anemias. The mechanism of action of endogenous erythropoietin and the therapeutic use of epoetin alfa to stimulate red blood cell production and improve the quality of life in cancer patients are reviewed here. Epoetin alfa may also attenuate the cognitive dysfunction associated with cancer therapy. Interestingly, functional endogenous erythropoietin receptor signaling pathways have been demonstrated in numerous nonerythropoietic tissues. Of particular importance, epoetin alfa confers neurotrophic and neuroprotective effects in cultured neurons and in several animal models for neurologic disease. In one clinical trial, epoetin alfa appeared to limit functional and histologic damage in patients with stroke. Therefore, in cancer patients receiving chemotherapy, the beneficial effects of epoetin alfa could be mediated not only through enhanced erythrocyte production but also via direct effects on the nervous system. Further investigation into the nonerythropoietic effects of epoetin alfa could broaden its clinical utility for patients with cancer and also provide new therapies for various neurologic disorders.

Topics: Anemia; Apoptosis; Epoetin Alfa; Erythropoiesis; Erythropoietin; Humans; Neoplasms; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins; Signal Transduction

To describe the management of fatigue and anemia in patients with cancer.. Published literature and clinical experience.. Anemia is a common cause of cancer-related fatigue. Epoetin alfa increases hemoglobin, decreases transfusion requirements, and improves energy and quality of life in patients with cancer-related anemia. Nonpharmacologic treatment options include exercise, nutrition optimization, and psychosocial interventions. Effective management of fatigue improves overall cancer treatment, quality of life, and functional status.. Fatigue and anemia are commonly undertreated complications of cancer and its treatment. Oncology nurses play a key role in identifying and managing these conditions.

Topics: Activities of Daily Living; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Humans; Male; Neoplasms; Nursing Assessment; Nursing Methodology Research; Oncology Nursing; Patient Care Planning; Quality of Life; Recombinant Proteins

As the major regulator of erythropoiesis in man, erythropoietin inhibits the programmed cell death of committed erythroid precursors. In cancer patients, a relative erythropoietin deficiency is coupled with a decreased responsiveness to the substance mediated by the effects of inflammatory cytokines on the marrow and on ferrokinetics, leading to a high incidence of anemia. Two recombinant human erythropoietin (rhEPO) preparations--epoetin alfa (Epogen, Procrit) and epoetin beta (Marogen)--as well as a modified erythropoietic compound (darbepoetin alfa [Aranesp]) are in clinical use. Part 2 of this two-part series on hematopoietic agents reviews the use of these erythropoietic factors and their effect on the anemia that develops in cancer patients. Thrombopoietic factors and progenitor cell-mobilizing factors are also briefly addressed.

Topics: Anemia, Aplastic; Erythropoietin; Hematinics; Humans; Medical Oncology; Myelodysplastic Syndromes; Neoplasms; Practice Patterns, Physicians'; Quality of Life; Recombinant Proteins

Cancer-related anemia often develops from the infiltration of marrow by malignant cells, impaired hemoglobin (Hb) production related to chemotherapy or radiation therapy, iron deficiency, or low endogenous erythropoietin levels. Patients with cancer-related anemia may experience cognitive dysfunction including decreased mental alertness, poor concentration, and memory problems. Anemia-mediated cerebral hypoxia may cause symptoms such as headache, vertigo, tinnitus, and dizziness. These symptoms often are exacerbated in the elderly patient with cancer and related to underlying low Hb concentrations. Restoring Hb levels via the administration of iron supplements, blood transfusions, or, more recently, erythropoiesis-stimulating therapy (epoetin alfa) results in significant improvement of cognitive function. The use of epoetin alfa as a treatment option for patients with chemotherapy-associated anemia and an Hb concentration less than 10 g/dL has been recommended by the American Society of Clinical Oncology and the American Society of Hematology. Erythropoiesis-stimulating therapies are a promising treatment option for cancer-related anemia that may improve cognitive function and quality of life for patients with cancer.

Topics: Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Cognition Disorders; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Neoplasms; Recombinant Proteins

Anemia is a chronic condition that affects many patients with chronic kidney disease (CKD). These patients often require recombinant human erythropoietin (rHuEPO) to stimulate bone marrow to produce red blood cells. The agent often has to be administered 2-3 times/week for maximum efficacy A new product, darbepoetin-alpha, is a hyperglycosylated erythropoiesis-stimulating protein that has a longer terminal half-life than rHuEPO (25.3 vs 8.5 hrs), which allows for less frequent dosing. At an equivalent dosage as rHuEPO, darbepoetin-alpha maintains hemoglobin values within target range and has a similar adverse effect profile. It is safe and effective for treatment of anemia of CKD. Pharmacoeconomic and quality-of-life studies are warranted to determine the compound's overall benefit.

Topics: Clinical Trials as Topic; Darbepoetin alfa; Doping in Sports; Erythropoietin; Humans; Kidney Diseases; Neoplasms

Erythropoietin, in its standard role for the treatment of anemia, is often mechanistically regarded simply as increasing blood oxygen-carrying capacity and hence decreasing tumor hypoxia. In reality, erythropoietin (a member of the cytokine superfamily) is expressed in a multitude of tissues/cell types including erythroid and cancer cells, and the liver and central nervous system. Erythropoietin expression is induced by hypoxia-inducible factor-1, which itself is induced during hypoxia. Whereas it has no endogenous tyrosine kinase activity of its own, erythropoietin, via constitutively associated JAK2, can activate several signaling pathways including STAT5, RAS, and phosphoinositol 3-kinase. An increased understanding of these pathways is already opening up new clinical indications, particularly in terms of oncology and neurology. Current arrays/molecular endpoint studies in clinical trials should identify key components of the particular signaling pathways that will guide further use in the development of both better synergistic therapies as well as new molecular targets.

Topics: Anemia; Cognition Disorders; Erythropoietin; Humans; Neoplasms; Oligonucleotide Array Sequence Analysis; Receptors, Erythropoietin; Recombinant Proteins; Signal Transduction

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Controlled Clinical Trials as Topic; Energy Metabolism; Erythropoietin; Fatigue; Female; Humans; Male; Neoplasms; Patient Satisfaction; Prognosis; Quality of Life; Recombinant Proteins; Retrospective Studies; Treatment Outcome

Children with cancer frequently develop anemia both from the disease and from chemo- and radiotherapy. Considered a manageable complication, anemia is often not treated until it becomes severe, i.e., hemoglobin (Hb) level

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Child; Child, Preschool; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Infant; Infant, Newborn; Male; Neoplasms; Recombinant Proteins; Retrospective Studies; Risk Assessment; Treatment Outcome

Numerous reports on recombinant human erythropoietin (rHuEPO, epoetin alfa) treatment of cancer-related anemia in adult patients have been published to date. These have shown that epoetin increases hemoglobin levels, significantly ameliorates symptoms of anemia, and improves adult patients' quality of life. Unfortunately, less is known about the impact of epoetin on anemia in pediatric cancer patients.. It is the objective of this review to summarize and analyze data of clinical trials of epoetin treatment of anemia in pediatric cancer patients.. A total of 15 studies were reviewed; eight were considered for detailed analysis and demonstrated important variabilities in study methods. Four of the eight were controlled, randomized trials and four were open label.. These studies suggested an overall beneficial effect of epoetin alfa for treating anemia in children with cancer. Three large, multicenter clinical trials of the efficacy and safety of epoetin alfa in anemic children with cancer are currently underway, one in Europe and two in North America.

Topics: Anemia; Child; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Medical Oncology; Multicenter Studies as Topic; Neoplasms; Pediatrics; Randomized Controlled Trials as Topic; Recombinant Proteins

Topics: Anemia; Darbepoetin alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Neoplasms

Darbepoetin alfa is a new erythropoiesis-stimulating protein that has five carbohydrate chains compared with three in recombinant human erythropoietin (r-HuEPO, epoetin alfa). Owing to its increased carbohydrate content, the terminal half-life of darbepoetin alfa is 2-3-fold greater than that of r-HuEPO in patients with chronic kidney disease or cancer. This pharmacokinetic property may allow for less frequent administration of darbepoetin alfa compared with r-HuEPO. Although several regimens are still being tested, a predictable increase was observed in serum concentrations of darbepoetin alfa and no clinically relevant accumulation was seen with once-weekly administration for up to 48 weeks. Preliminary data in patients with cancer suggest that concurrent chemotherapy may influence the pharmacokinetics of darbepoetin alfa. Therefore, the timing of dosing relative to chemotherapy may be important. Darbepoetin alfa, through its potential for less frequent dosing, offers a more convenient treatment option than r-HuEPO for patients with anemia secondary to cancer or kidney disease.

Topics: Anemia; Animals; Antineoplastic Agents; Area Under Curve; Biological Availability; Clinical Trials as Topic; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Neoplasms

Cancer-associated anemia is common and has many causes, including the effects of the underlying disease and cancer treatment. The effect of anemia on patients with cancer was not appreciated fully until relatively recently. Several well-designed studies have demonstrated the relationship between anemia and fatigue, and the effect of fatigue on quality of life. These data have resulted in a greater awareness of anemia in cancer and have increased the use of recombinant human erythropoietin (r-HuEPO, epoetin alfa) therapy for the treatment of anemia. Recombinant HuEPO produces a hemoglobin response in 50-60% of patients with cancer; however, to obtain this response rate, frequent dosing is required. Darbepoetin alfa, a recently developed erythropoietic protein, has a longer half-life than that of r-HuEPO, enabling less frequent dosing, and has a greater in vivo activity. In studies of patients with cancer who develop anemia, darbepoetin alfa has proved to be well tolerated and effective, and its advantages make it a potential improved treatment option for anemia in these patients.

Topics: Anemia; Clinical Trials as Topic; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

Recombinant human erythropoietin (r-HuEPO, epoetin alfa), is an established and effective treatment for anemia associated with both chronic kidney disease (CKD) and cancer and has improved the management of anemia over alternatives such as transfusion. Darbepoetin alfa is a new erythropoietic agent with a 3-fold longer half-life and increased in vivo potency relative to r-HuEPO. These properties allow patients to be treated with longer dosing intervals than with r-HuEPO. Relative potency between r-HuEPO and darbepoetin alfa is not a fixed relationship but is dependent on several factors. Clinical study results suggest that greater relative potency differences are seen between r-HuEPO and darbepoetin alfa when the dosing intervals are longer and when r-HuEPO dose requirements are higher. Although 200 U of r-HuEPO contains the same peptide mass as 1 microg of darbepoetin alfa, a fixed ratio of 200:1 does not necessarily predict an appropriate dose conversion between the two drugs across the entire spectrum of dose ranges. When converting patients with CKD from r-HuEPO to darbepoetin alfa, dosing should be based on relevant clinical data. Appropriate guidance for conversion of patients with CKD from r-HuEPO to darbepoetin alfa is provided in the approved United States package insert for darbepoetin alfa. In patients who are prescribed darbepoetin alfa, either by conversion from r-HuEPO or as de novo treatment, therapy should begin according to recommendations in the package insert, after which, doses should be titrated individually according to each patient's hemoglobin response. Dosing data from oncology clinical studies, although not necessarily applicable to CKD, indicate similar potency ratios between r-HuEPO and darbepoetin alfa, and in addition affirm the finding that, as the interval between doses of darbepoetin alfa is increased, hemoglobin response is maintained.

Topics: Anemia; Clinical Trials as Topic; Darbepoetin alfa; Drug Administration Schedule; Drug Labeling; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Injections, Intravenous; Kidney Failure, Chronic; Neoplasms; Recombinant Proteins; Therapeutic Equivalency

Erythropoietin has been successfully used in the treatment of cancer-related anaemia. About two-thirds of patients with the 'anaemia of chronic disorders', anaemia due to neoplastic bone marrow infiltration or therapy-related anaemia, are expected to respond to high doses of erythropoietin with a haemoglobin increase of at least 2 g/dl. In the myelodysplastic syndromes, about one-third of patients will show a response when very high doses of erythropoietin are combined with granulocyte colony-stimulating factor. The response to erythropoietin is slow, requiring several months to develop. Various factors have been reported to predict a response, but the prediction models proposed are contradictory and have not been prospectively validated. Therefore, the most common strategy to determine the responsiveness of cancer-related anaemia to erythropoietin is to subject the patient to a treatment trial of several months' duration. Treatment with erythropoietin needs to be compared with the transfusion of red blood cells, which has similar effects on the patient's haemoglobin level. Erythropoietin is a generally well tolerated drug, but it is slow to exert an effect and ineffective in a substantial proportion of patients. Red blood cell transfusion is associated with a small risk of infectious, allergic or toxic complications, but it leads to a rapid haemoglobin increase in virtually all patients treated. Cost and cost-benefit analyses from several countries indicate that, in patients with cancer-related anaemia, treatment with erythropoietin is considerably more expensive than the transfusion of allogeneic red blood cells. Thus, the choice between the two treatment options will be influenced by the financial resources of the respective healthcare systems.

Topics: Anemia; Cost-Benefit Analysis; Erythropoietin; Humans; Neoplasms; Patients

This study was designed to evaluate if erythropoietin (EPO) is effective in the treatment of cancer related anemia, and if its effect remains unchanged when data are analyzed according to various clinical and methodological characteristics of the studies. We also wanted to demonstrate that cumulative meta-analysis (CMA) can be used to resolve uncertainty regarding clinical questions.. Systematic Review (SR) of the published literature on the role of EPO in cancer-related anemia. A cumulative meta-analysis (CMA) using a conservative approach was performed to determine the point in time when uncertainty about the effect of EPO on transfusion-related outcomes could be considered resolved.. Patients included in randomized studies that compared EPO versus no therapy or placebo.. Number of patients requiring transfusions.. Nineteen trials were included. The pooled results indicated a significant effect of EPO in reducing the number of patients requiring transfusions [odds ratio (OR) = 0.41; 95%CI: 0.33 to 0.5; p < 0.00001;relative risk (RR) = 0.61; 95% CI: 0.54 to 0.68]. The results remain unchanged after the sensitivity analyses were performed according to the various clinical and methodological characteristics of the studies. The heterogeneity was less pronounced when OR was used instead of RR as the measure of the summary point estimate. Analysis according to OR was not heterogeneous, but the pooled RR was highly heterogeneous. A stepwise metaregression analysis did point to the possibility that treatment effect could have been exaggerated by inadequacy in allocation concealment and that larger treatment effects are seen at hb level > 11.5 g/dl. We identified 1995 as the point in time when a statistically significant effect of EPO was demonstrated and after which we considered that uncertainty about EPO efficacy was resolved.. EPO is effective in the treatment of anemia in cancer patients. This could have already been known in 1995 if a CMA had been performed at that time.

Topics: Anemia; Erythrocyte Transfusion; Erythropoietin; Humans; Kinetics; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins

Anemia in cancer patients is associated with a decline in energy levels, activity levels, and quality of life, and these variables improve when hemoglobin levels rise. Importantly, the impact of improved hemoglobin levels on response to chemotherapy, radiation therapy, and survival time is under study. This line of research follows favorable preliminary data in clinical studies suggesting improved treatment outcomes with reversal of anemia. It is estimated that there are 10 million people in the United States with cancer. Of the 1.3 million cancer patients who are anemic with hemoglobin levels less than 12 g/dL, about 800,000 are receiving chemotherapy and 500,000 are not. The predominant treatable cause of anemia in these patients is a relative lack of erythropoietin; overall, only 20% of anemic cancer patients receive a trial of erythropoietic therapy. About one-fourth (26%) of patients whose hemoglobin is less than 12 g/dL and who are receiving chemotherapy for cancer are currently receiving erythropoietic therapy. A review of the patients in our oncology practice revealed that 37% were anemic (hemoglobin < 12 g/dL) prior to chemotherapy, and an additional 41% became anemic during chemotherapy. Overall, 63% of our cancer patients on chemotherapy received erythropoietin; 6% of these patients received red cell transfusions. Only 7% of our patients had a hemoglobin level < 10 g/dL before chemotherapy; overall, 80% of our patients maintained hemoglobin levels > or = 10 g/dL at all times. Barriers to the use of erythropoietic agents include cost and reimbursement issues, inconvenience of frequent injections, limitations in efficacy, and indication restrictions. An understanding of the importance of anemia and newer agents requiring less frequent dosing, such as darbepoetin alfa (Aranesp), may help physicians and patients overcome some of these barriers.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Recombinant Proteins; United States

The clinical development of recombinant human erythropoietin (rHuEPO) has had a remarkable impact on the clinical practice of oncology. A decade ago, randomized, placebo-controlled trials in anemic cancer patients demonstrated that rHuEPO resulted in an improvement in hemoglobin and hematocrit, a reduction in transfusion requirements, and improvement in quality-of-life (QOL) end points. Based on these trials, recombinant erythropoietin was approved for the treatment of anemia in patients with nonmyeloid malignancies in whom the anemia was caused by the effect of chemotherapy. The clinical indication was to decrease the needfor transfusion in patients for whom anemia was not due to other reversible causes. Despite this broad indication, the incorporation of rHuEPO in clinical practice was limited because of a variety of factors, including physician perception that mild-to-moderate anemia in the cancer patient was generally asymptomatic and did not warrant intervention. Subsequently, three large open-label, prospective trials of recombinant erythropoietin were performed in the community setting in anemic cancer chemotherapy patients. All three trials replicated the results of the original randomized study, but with a much larger database of more than 7,000 patients. Importantly, these trials were able to define the major impact of hemoglobin level on quality of life. Patients on these trials who improved their hemoglobin > 2 g/dL or achieved a hemoglobin > or = 12 g/ dL had the greatest improvement in symptoms of energy, activities of daily living, and overall quality of life. Furthermore, a once-per-week dosing schedule was found to be comparable to three-times-weekly administration of rHuEPO. A European randomized, placebo-controlled trial confirmed these QOL results, and a meta-analysis of other randomized clinical trials firmly supports the role of erythropoietin therapy in improving hemoglobin levels and reducing transfusion requirements. Based on this aggregate of data, the use of erythropoietin in the treatment of mild-to-moderate anemia has become a standard of care. These studies have also expanded our understanding of the problem of fatigue and the study of interventions that can improve quality of life for cancer patients.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins

Anemia is the most common hematologic abnormality seen in patients with cancer. Anemia is associated with debilitating symptoms and poorer health-related quality of life and may result in less than optimal disease/treatment outcomes. The high prevalence of anemia and the potential clinical and prognostic impact make it important to have a systematic approach to the diagnosis and treatment of cancer-related anemia. A rigorous diagnostic evaluation should be undertaken to identify the cause of anemia and guide appropriate treatment. Treatment of anemia with erythropoiesis stimulating proteins offers an alternative treatment to red blood cell transfusions and has been shown to improve quality of life for patients being treated for cancer. In addition, recent studies suggest improved cancer treatment outcomes. Data indicate that treatment with darbepoetin alfa, a novel erythropoiesis stimulating protein, improves hemoglobin levels and quality of life in anemic patients with cancer who are not receiving chemotherapy or radiotherapy. Symptoms of anemia, when searched for properly, are identified often at hemoglobin levels less than 12 g/dL. As the understanding of the importance of anemia grows, and more convenient methods of therapy become available, patients will benefit with a more proactive approach to early treatment or prevention of this complication of cancer and its treatment.

Topics: Anemia; Blood Transfusion; Clinical Trials as Topic; Darbepoetin alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Physician's Role; Quality of Life

Barriers to use of erythropoietic therapy in cancer patients include nonresponse in a sizable proportion, resultant lowering of cost-effectiveness, and inconvenience. Darbepoetin alfa represents the outcome of efforts to develop agents with improved erythropoietic potency. This agent has been shown to produce high dose-related response rates, reduce risk of transfusion, and produce dose-related rapidity of response in cancer patients; no loss in dose-efficiency is observed with once-every-2-week dosing compared with weekly dosing, and the feasibility of every-3-week dosing has been demonstrated. In addition, the characteristics of this agent may permit a treatment schedule consisting of front loading with an optimal dose followed by low-dose maintenance, which may further improve dose-efficiency and cost-effectiveness of treatment. The characteristics of darbepoetin alfa suggest the ability to improve overall quality of erythropoietic therapy, which may increase its utilization in patients who would benefit from such treatment.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Darbepoetin alfa; Drug Administration Schedule; Erythropoietin; Hemoglobins; Humans; Neoplasms; Recombinant Proteins

This article examines the relationships between chemotherapy-induced anemia, fatigue, and psychological distress among anemic cancer patients with solid tumors. Patients participating in two randomized clinical trials evaluating the efficacy of darbepoetin alfa (Aranesp) completed a questionnaire at baseline, at the beginning of each chemotherapy cycle, and at the end of the 12-week treatment period. The questionnaire included four psychological distress outcomes: Brief Symptom Inventory (BSI) Depression and Anxiety, Functional Assessment of Cancer Therapy (FACT)-Emotional Well-Being, numeric rating scale of Overall Health, and the FACT-Fatigue subscale. Patients with a hemoglobin response of at least a 2 g/dL increase were more likely to experience meaningful improvements (at least 3 points) in FACT-Fatigue scores than nonresponders (55.0% vs 39.8%; P = .0004). Patients with meaningful improvements in FACT-Fatigue scores reported significantly greater improvements in each of the psychological outcomes relative to those without improved fatigue (P <.0001). For BSI Depression and Anxiety, the differences in mean change scores between patients with and without improved fatigue were 8.2 and 7.7, respectively. Improving the hemoglobin levels of patients undergoing chemotherapy and suffering from anemia-related fatigue has the potential to produce significant positive effects on patients' fatigue, depressive symptoms, anxiety, feelings of helplessness, and overall health.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Darbepoetin alfa; Erythropoietin; Fatigue; Female; Humans; Male; Mental Disorders; Neoplasms; Quality of Life

Anemia, common in people with cancer, can be due to the disease itself or to the associated therapy. Fatigue, the most prevalent of all symptoms experienced by cancer patients, is the primary symptom of anemia. Caused by many factors,fatigue, regardless of etiology, has an adverse impact on health-related quality of life. Anemia is among the more treatable of those causes. Prior to the development of recombinant human erythropoietin, red blood cell transfusion was the standard treatment for cancer-related anemia. Erythropoietic agents are an effective alternative to blood transfusion: they improve hematocrit, reduce transfusion dependency, and eliminate transfusion-related risks. Although studies are mixed, most clinical trials have also suggested that erythropoietic agents have a positive impact upon cancer patients' quality of life. However, the cost of drug supply is quite high in the oncology setting, where much higher doses are required relative to the nephrology setting. Thus, although few challenge the treatment's effectiveness, cost-effectiveness remains an open question. The data collected over the years to address these questions have helped define and clarify the relationship between anemia and health-related quality of life in people with cancer. That relationship is summarized in this article.

Topics: Anemia; Clinical Trials as Topic; Erythropoietin; Fatigue; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Quality of Life

The AINT/ERIC/TACC genes encode novel proteins with a coiled coil domain at their C-terminus. The founding member of this expanding family of genes, transforming acidic coiled coil 1 (TACC1), was isolated from a BAC contig spanning the breast cancer amplicon-1 on 8p11. Transfection of cells in vitro with TACC1 resulted in anchorage-independent growth consistent with a more "neoplastic" phenotype. Database searches employing the human TACC1 sequence revealed other novel genes, TACC2 and TACC3, with substantial sequence homology particularly in the C-terminal regions encoding the coiled coil domains. TACC2, located at 10q26, is similar to anti-zuai-1 (AZU-1), a candidate breast tumour suppressor gene, and ECTACC, an endothelial cell TACC which is upregulated by erythropoietin (Epo). The murine homologue of TACC3, murine erythropoietin-induced cDNA (mERIC-1) was also found to be upregulated by Epo in the Friend virus anaemia (FVA) model by differential display-PCR. Human ERIC-1, located at 4p16.3, has been cloned and encodes an 838-amino acid protein whose N- and C-terminal regions are highly homologous to the shorter 558-amino acid murine protein, mERIC-1. In contrast, the central portions of these proteins differ markedly. The murine protein contains four 24 amino acid imperfect repeats. ARNT interacting protein (AINT), a protein expressed during embryonic development in the mouse, binds through its coiled coil region to the aryl hydrocarbon nuclear translocator protein (ARNT) and has a central portion that contains seven of the 24 amino acid repeats found in mERIC-1. Thus mERIC-1 and AINT appear to be developmentally regulated alternative transcripts of the gene. Most members of the TACC family discovered so far contain a novel nine amino acid putative phosphorylation site with the pattern [R/K]-X(3)-[E]-X(3)-Y. Genes with sequence homology to the AINT/ERIC/TACC family in other species include maskin in Xenopus, D-TACC in Drosophila and TACC4 in the rabbit. Maskin contains a peptide sequence conserved among eIF-4E binding proteins that is involved in oocyte development. D-TACC cooperates with another conserved microtubule-associated protein Msps to stabilise spindle poles during cell division. The diversity of function already attributed to this protein family, including both transforming and tumour suppressor properties, should ensure that a new and interesting narrative is about to unfold.

Topics: Animals; Carrier Proteins; Erythropoietin; Fetal Proteins; Gene Expression Regulation; Humans; Mice; Microtubule-Associated Proteins; Neoplasms; Nuclear Proteins; Phylogeny; Spindle Apparatus

The majority of cancer patients suffer from chronic anemia. While recombinant human erythropoietin (rHuEPO) offers many of the advantages of blood transfusions, response rates to this treatment are variable and in some trials a large proportion of patients (30 50%) did not respond. This failure may be due to factors related to the underlying disease, the chemotherapy given or functional iron deficiency. An accurate means of predicting response to rHuEPO would be beneficial to both healthcare providers and patients.. Data were identified by searches of the published literature, including PubMed, references from relevant reviews, and abstracts presented at recent international oncology and hematology meetings. Only papers in English published between 1990 and 2002 were included. References were selected according to direct relevance to the topic discussed and availability.. The best algorithms for predicting response appear to be those combining an assessment of the adequacy of endogenous erythropoietin production together with some early indicators of erythropoietic marrow response. Further characterization of the dose-response relationship of erythropoietic agents may allow better understanding of ways in which response may be enhanced. Adequate iron availability could also contribute to better response rates.. Further characterization of the predictors of response for current and upcoming erythropoietic agents may enhance the management of anemia associated with cancer, and provide more convenient, effective, and flexible therapy.

Topics: Algorithms; Anemia; Data Collection; Dose-Response Relationship, Drug; Erythropoietin; Humans; Neoplasms; Prognosis; Recombinant Proteins; Treatment Outcome

Cancer-related anemia, in addition to having detrimental effects on quality of life and adding the risk and inconvenience of blood transfusions, may also be associated with decreased survival or time to progression. Yet despite increasing awareness of the value of treating cancer-related anemia, over 60% of US cancer patients receiving chemotherapy who have hemoglobin values below 10 g/dL are not treated for this condition. Current treatment options include red blood cell transfusions, iron supplementation for iron deficiency, or erythropoietic agents, including recombinant human erythropoietin (rHuEPO) and darbepoetin alfa (Aranesp). The articles in this supplement describe the basic scientific research and clinical development of darbepoetin alfa--another safe, effective, and approved treatment for chemotherapy-induced anemia.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Darbepoetin alfa; Erythropoietin; Humans; Neoplasms

Many cancer patients suffer from anemia, which has a major detrimental effect on their quality of life. Recombinant human erythropoietin (rHuEPO) is now widely used in cancer patients, as it improves hematocrit, lowers blood transfusion requirements, and improves quality of life. Recent research indicates that EPO has pleiotropic effects on the body well beyond the maintenance of red cell mass, but the mechanisms involved in relieving fatigue and improving quality of life in cancer patients are poorly understood. EPO receptors (EPO-Rs) have been detected in many different cells and tissues, providing evidence for autocrine, paracrine, and endocrine functions of EPO. Apart from its endocrine function, EPO may have a generalized role as an antiapoptotic agent that is associated with enhancement of muscle tone, mucosal status, and gonadal and cognitive function. The recent discovery of EPO-Rs in breast tumor vasculature, while raising important questions about the possible effects of pharmacological doses of rHuEPO on tumor cells, also suggests that the receptors could provide a useful target for drugs attached to EPO.

Topics: Anemia; Endocrine System; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

As the antitumor activity of radiation is mediated via its interaction with oxygen to form labile free radicals, the intratumoral oxygen level has an important influence on the ability of radiation therapy to kill malignant cells. By decreasing the oxygen-carrying capacity of the blood, anemia may result in tumor hypoxia and may have a negative influence on the outcome of radiotherapy for various malignancies, even for small tumors not normally assumed to be hypoxic. In addition, anemia also has a negative effect on the quality of life of cancer patients, as evidenced by worsening fatigue. As a high proportion (about 50%) of cancer patients undergoing radiotherapy are anemic prior to or during treatment, strategies to correct anemia and/or the resultant tumor hypoxia are increasingly being considered an important component of treatment. In particular, epoetin alfa (recombinant human erythropoietin), which has proved an effective and well-tolerated means of raising hemoglobin levels in anemic patients receiving radiotherapy, potentially could reverse the negative prognostic influence of a low hemoglobin in patients with certain malignancies. Radiation oncologists need to be aware of the possibility of anemia in cancer patients undergoing radiotherapy so that timely intervention can be instituted whenever anemia is diagnosed.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Peripheral Nervous System Diseases; Predictive Value of Tests; Prevalence; Prognosis; Quality of Life; Radiotherapy; Recombinant Proteins; Survival Analysis; Treatment Outcome

Although the association between low hemoglobin levels and poorer outcomes in radiation oncology has long been recognized, anemia is often overlooked and untreated. However, a growing body of clinical evidence now indicates that low hemoglobin levels during radiation treatment are associated with decreased response and survival following radiotherapy. For example, a large Canadian retrospective study in patients receiving radical radiotherapy for cervical cancer showed that the 5-year survival rate was 19% higher in those whose hemoglobin during radiation treatment was =12 g/dl compared to those with levels <12 g/dl. The data suggest that clinical trials need to be performed to determine whether increasing hemoglobin levels leads to improved local control and survival. The mechanism by which low hemoglobin levels could cause poorer outcomes is not well understood and needs further elucidation. It is postulated that lower hemoglobin levels resulting in decreased oxygen carrying capacity may lead to increased tumor hypoxia, radiation resistance and increased tumor angiogenesis. The interrelationship of low hemoglobin levels, hypoxia, tumor angiogenesis and survival is explored in this article.

Topics: Anemia; Cell Hypoxia; Chemotherapy, Adjuvant; Epoetin Alfa; Erythropoietin; Female; Head and Neck Neoplasms; Hematinics; Hemoglobins; Humans; Neoplasms; Neovascularization, Pathologic; Radiotherapy, Adjuvant; Recombinant Proteins; Survival Analysis; Survival Rate; Uterine Cervical Neoplasms

Cancer patients frequently experience anemia as a complication of chemotherapy. Recent advances in assessing the relationships between anemia, fatigue and quality of life (QOL) in such patients have resulted in a new multidimensional perspective of these parameters. Clinical data suggest that even a mild-to-moderate chemotherapy-induced anemia results in a significant reduction in a patient's energy level and QOL. As recombinant human erythropoetin has recently become available for the treatment of this condition, we performed a review of the incidence and severity of anemia associated with commonly employed chemotherapy regimens in the major non-hematologic malignancies. Although evident flaws in the grading and reporting of treatment-related anemia have limited analysis, the results clearly indicate a relatively high incidence of mild-to-moderate anemia. Research in progress is likely to result in a new classification of chemotherapy-induced anemia that can guide therapeutic interventions on the basis of outcomes and hemoglobin levels. The once widespread belief that lesser degrees of anemia must be endured without treatment may be overcome as greater emphasis is placed on the QOL of the oncology patient. Further insights into the relationships between hemoglobin levels, patient well-being and symptoms may lead to a refinement of current strategies of approaching the treatment of anemia.

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Humans; Incidence; Neoplasms; Recombinant Proteins; Severity of Illness Index

Anemia management programs typically strive to maintain hemoglobin (Hb) levels in the target range of 11 to 12 g/dL recommended by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI). Although nephrology clinicians are constantly alert for conditions that cause hyporesponse to Epoetin alfa therapy, management protocols generally focus on assessing and managing acute disorders that affect the production of red blood cells. A more difficult clinical challenge is how to systematically manage patients with conditions that chronically affect the erythropoietic response and are intractable to routine therapies. This article addresses the etiology and management of chronic conditions that require a specialized anemia management approach to ensure that patients can achieve targeted Hb levels and associated clinical and quality of life benefits. Examples include chronic inflammatory disorders, severe secondary hyperparathyroidism, malignancies, human immunodeficiency virus (HIV), and kidney transplant failure.

Topics: Aged; Anemia; Chronic Disease; Erythropoiesis; Erythropoietin; Female; HIV Infections; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Neoplasms

Anemia in cancer patients is frequent but often under-recognized and under-treated. This may be related to misconceptions about the impact of anemia on cancer patients and ill-defined guidelines for treatment, as well as the inadequacies of current therapy. Darbepoetin alfa, a novel erythropoiesis-stimulating protein with a longer serum half-life than epoetin (alpha and beta), is approved to treat anemia in patients with chronic kidney disease. Most recently darbepoetin alfa has received approval by the FDA in USA for the treatment of anemia associated with myelosuppressive chemotherapy and approval in the EU is expected soon. Clinical trials in cancer patients indicate that darbepoetin alfa effectively and safely alleviates anemia in patients receiving chemotherapy. A Phase II trial also indicates that darbepoetin alfa is effective in patients who are not receiving chemotherapy. Thus, darbepoetin alfa has the potential to improve supportive care and thereby, cancer patients' quality of life, and might also impact on treatment outcome.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Interactions; Erythropoietin; Humans; Neoplasms; Quality of Life

Iron plays an essential role in immunosurveillance, because of its growth promoting and differentiation inducing properties for immune cells and its interference with cell mediated immune effector pathways and cytokine activities. At the same time, iron is crucial for the proliferation of tumour cells and micro-organisms, due to its role in mitochondrial respiration and DNA synthesis. Thus, gaining control over iron homeostasis is of vital importance for the course of an infection or a tumour disease, since increased iron availability or iron overload of the immune system are associated with an unfavourable course of many of these diseases. The most frequent clinical condition demonstrating this interaction of iron and immunity is anaemia of chronic disease (ACD). ACD develops in patients with chronic activation of cellular immunity such as subjects suffering from malignancies, auto-immune disorders or infections. ACD may be seen as an immune driven disease since cytokines and their products cause (i) a diversion of iron traffic into the reticuloendothelial systems, thus limiting the availability of the metal to erythroid progenitor cells for haem biosynthesis, (ii) an inhibition of erythroid progenitor cell proliferation and (iii) blunted production and activity of erythropoietin (EPO). However, ACD may also hold some benefit by reducing iron availability to invading pathogens, thus limiting their growth, and by stimulating cell mediated immune function. The latter can be referred to the correction of an inhibitory effect of iron towards IFN-gamma induced immune effector pathways in macrophages. Whereas ACD can be easily diagnosed based on the characteristic changes of iron homeostasis, therapy of ACD is much more controversial. Where a cure of the underlying disease is impossible, transfusions for rapid correction of haemoglobin levels and human recombinant EPO can be used with varying success. The sole application of iron should be strictly avoided due to promotion of pathogen growth and impairment of immune function.

Topics: Anemia, Hypochromic; Bacterial Infections; Cytokines; Erythroid Precursor Cells; Erythropoietin; Heme; Hemochromatosis; Humans; Immune Tolerance; Immunity, Cellular; Iron; Macrophages; Neoplasms

Anaemia occurs in a significant number of patients with cancer, and is associated with symptoms of fatigue, dizziness, headache and decreased health-related quality of life. Clinical trials have demonstrated the ability of epoetin alfa to increase haemoglobin concentrations and reduce transfusion requirements in patients with cancer. Data from three large, open-label, community-based trials of >7000 patients, as well as a series of smaller, randomized, placebo-controlled studies, have confirmed the efficacy of treatment with epoetin alfa in patients undergoing chemotherapy. In two of the community-based studies (>2000 patients in each), patients undergoing chemotherapy received epoetin alfa, 150-300 IU/kg or 10,000-20,000 IU, three times weekly. Significant (P<0.01) increases in haemoglobin concentrations and reductions in transfusion rates were seen in both studies. Significant improvements in quality of life were also reported, as measured by the Linear Analogue Scale Assessment and the Functional Assessment of Cancer Therapy-Anaemia. Importantly, the increases in quality of life were independent of tumour response. These findings were also observed in randomized, placebo-controlled studies. The third study, in approximately 3000 patients, evaluated the efficacy of once-weekly dosing, which significantly (P<0.01) increased haemoglobin concentrations, reduced transfusion requirements and improved quality of life. Greater increases in haemoglobin concentration were associated with greater improvements in quality-of-life scores. The safety and efficacy profile of the once-weekly regimen was comparable with that of the three times weekly regimen. Maintaining optimal quality of life, while achieving tumour stabilization or regression, is essential to the successful management of patients with cancer. Epoetin alfa has been shown to increase haemoglobin concentration, decrease transfusion requirements and increase quality of life. Given the frequency of adverse sequelae associated with anaemia, its aggressive management should become an integral and routine part of cancer treatment.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Over the past decade an increasing number of studies have supported the use of recombinant human erythropoietin (epoetin) in cancer patients, suggesting that it improves haemoglobin concentrations for some. There is also evidence that this treatment may lead to improvement in quality of life for cancer patients. This systematic review examines the issue. We identified and critically reviewed 13 trials. Although some of the results indicate that epoetin has positive effects on quality of life, methodological limitations inherent in most of the studies hamper interpretation of data. Evidence from this review suggests that more robust designs are required to show any significant quality-of-life benefits for cancer patients undergoing epoetin treatment.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Controlled Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Injections, Subcutaneous; Male; Neoplasms; Quality of Life; Recombinant Proteins; Sensitivity and Specificity

Cells undergo a variety of biological responses when placed in hypoxic conditions, including activation of signalling pathways that regulate proliferation, angiogenesis and death. Cancer cells have adapted these pathways, allowing tumours to survive and even grow under hypoxic conditions, and tumour hypoxia is associated with poor prognosis and resistance to radiation therapy. Many elements of the hypoxia-response pathway are therefore good candidates for therapeutic targeting.

Topics: Animals; Antineoplastic Agents; Apoptosis; Aryl Hydrocarbon Receptor Nuclear Translocator; Basic Helix-Loop-Helix Transcription Factors; Cell Division; Cell Hypoxia; Cell Survival; Cyclic AMP Response Element-Binding Protein; Dimerization; DNA Damage; DNA-Binding Proteins; Embryonic and Fetal Development; Endothelial Growth Factors; Erythropoietin; Forecasting; Gene Expression Regulation; Glycolysis; Humans; Hydrogen-Ion Concentration; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Lymphokines; Mice; Neoplasms; Neovascularization, Pathologic; NF-kappa B; Nuclear Proteins; Oxidation-Reduction; Oxidative Stress; Oxygen; Prodrugs; Proto-Oncogene Proteins; Receptor Protein-Tyrosine Kinases; Receptors, Aryl Hydrocarbon; Signal Transduction; Trans-Activators; Transcription Factors; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factors; Xenograft Model Antitumor Assays

Darbepoietin-alpha is a novel erythropoiesis-stimulating protein that may help address some of the unmet needs of anemia treatment in patients with cancer. Compared with recombinant human erythropoietin, darbepoietin-alpha has increased sialylated carbohydrate content, associated with a prolonged serum half-life and increased in vivo biologic activity. Data from trials in patients with cancer with a range of tumor types, whether receiving chemotherapy or not, indicate that darbepoietin-alpha is effective in alleviating anemia when dosed at intervals of once every 1, 2, or 3 weeks and may effect greater and more rapid responses than recombinant human erythropoietin. Health-related quality of life benefits have been observed with darbepoietin-alpha treatment, and in a study of patients with small-cell lung cancer, darbepoietin-alpha was associated with increased progression-free survival. Administration of darbepoietin-alpha at extended dosing intervals offers the possibility of enhanced patient convenience and compliance and a reduced burden on healthcare resources. Confirmation of improved response and response times with this novel therapy may enable patients with cancer to benefit more rapidly.

Topics: Carcinoma, Small Cell; Darbepoetin alfa; Disease-Free Survival; Erythropoiesis; Erythropoietin; Humans; Lung Neoplasms; Neoplasms

Anemia is a common disorder in patients with cancer and can be caused by the disease itself or by cancer-related therapy. The cardinal symptom of anemia, fatigue, is the most commonly reported symptom in patients with cancer and has profound effects on patient well-being and quality of life. Until recently, blood transfusions were the mainstay of management of cancer-related anemia, despite attendant risks of transfusion-related reactions and transmission of infection. Recombinant human erythropoietin (epoetin-alpha), an effective alternative to blood transfusion, has been shown to improve hematologic parameters, including hemoglobin levels, Hematocrit, and transfusion requirements. Clinical trials have also suggested that this intervention has a positive impact on the quality of life of patients with cancer. The literature published between November 2000 and October 2001 continues to support a positive effect of epoetin-alpha therapy on the quality of life of patients with cancer and includes investigations of dosing schedules more convenient for patients and trials of longer-acting versions of epoetin-alpha, such as the novel erythropoiesis-stimulating protein. Future studies that incorporate measures of patient-reported outcomes and rigorous methodologic designs are needed to strengthen and elucidate this association between these pharmacologic therapies for cancer-related anemia and quality of life.

Topics: Anemia; Erythropoietin; Humans; Neoplasms; Quality of Life

Epoetin alfa has been in use for over a decade to increase hemoglobin in patients with cancer who develop chemotherapy-associated anemia. Early placebo-controlled, randomized studies, as well as recent large, community-based trials in thousands of patients, have consistently shown recombinant human erythropoietin (rHuEPO, epoetin alfa) to be effective and safe in the treatment of chemotherapy-associated anemia. Patients experienced an improved quality of life (QOL) related to the magnitude of the hemoglobin increase. As measured by a Linear Analog Scale Assessment, mean energy level, ability to do daily activities, and overall QOL improved significantly in patients who received epoetin alfa. The improvement in QOL was similar when anemia-specific instruments (Functional Assessment of Cancer Therapy-Anemia) were used. A large community-based trial has demonstrated that the more convenient once-weekly dosing schedule resulted in good efficacy and safety profiles. A recent double-blind placebo-controlled study that compared the efficacy of epoetin alfa versus placebo in patients receiving nonplatinum-based chemotherapy has confirmed epoetin alfa's efficacy, safety, and beneficial QOL effects. These findings should challenge current anemia management practices and encourage aggressive treatment of anemia in cancer patients receiving chemotherapy.

Topics: Aged; Anemia; Antineoplastic Agents; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins

Anaemia is common in patients with haematological malignancy, occurring in the majority of patients with malignant disease who are treated with chemotherapy. Most patients will have their anaemia attributed to the cytokine-mediated anaemia of chronic disease. Many of these patients with anaemia will be symptomatic with fatigue, which is the single most important symptom reported. Data from many studies indicate that treatment of patients with anaemia with recombinant human erythropoietin (rHuEpo) will increase their haemoglobin level, decrease transfusion need and also improve their quality of life. Recent clinical and experimental work suggest that improving the haemoglobin level may improve the patients' prognosis but this finding needs to be confirmed. Treatment of anaemia with rHuEpo in patients with cancer may produce many benefits. Unfortunately, rHuEpo is effective in only around 60% of patients, is slow acting and is expensive. These drawbacks have restricted its use in many healthcare systems. However, a failure to treat anaemia may have important adverse effects for the patient both in terms of their quality of life and, just possibly, in terms of their life expectancy.

Topics: Anemia; Anemia, Iron-Deficiency; Antineoplastic Agents; Blood Transfusion; Erythropoietin; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Survival Analysis

Topics: Colony-Stimulating Factors; Cytokines; Erythropoietin; Humans; Interferons; Interleukin-11; Interleukin-2; Neoplasms

Anaemia is a common occurrence in patients with cancer and contributes to the clinical symptomatology and reduced quality of life (QOL) seen in cancer patients. Many aspects of reduced QOL, including fatigue, are known to be associated with suboptimally low levels of haemoglobin. Even mild-to-moderate anaemia adversely affects patient-reported QOL parameters. Red blood cell transfusions are associated with many real and perceived risks, inconveniences, costs, and only temporary benefits. Recombinant human erythropoietin (rHuEPO) is an effective therapy to increase haemoglobin values in over half of anaemic cancer patients receiving concurrent chemotherapy. These increased haemoglobin values are closely correlated with improvements in QOL. Despite these objectively defined benefits, less than 50% of anaemic patients undergoing cytotoxic chemotherapy receive rHuEPO, in contrast to patients with chronic renal failure on dialysis, where anaemia is universally and aggressively treated to more optimal haemoglobin values. However, there are several barriers that may limit more widespread use of rHuEPO. These include inconvenience associated with frequent dosing; failure of a large proportion (40 to 50%) of patients to respond; relatively slow time to response; absence of reliable early indicators of response; and current lack of rigorous pharmacoeconomic data demonstrating cost-effectiveness. Darbepoetin alfa is a novel erythropoiesis stimulating protein (NESP) that is biochemically distinct from rHuEPO, and which has been proven to stimulate red blood cell production. The molecule has a 3-fold longer half-life and increased biological activity that will allow less frequent dosing, facilitating improved management of the anaemia of cancer. With this new option for therapy, further avenues of investigation should lead to renewed interest in the clinical benefits of optimal haemoglobin levels for patients with cancer.

Topics: Anemia; Antineoplastic Agents; Case Management; Clinical Trials as Topic; Darbepoetin alfa; Erythrocyte Transfusion; Erythropoietin; Fatigue; Forecasting; Health Care Costs; Humans; Hypoxia; Incidence; Kidney Failure, Chronic; Multicenter Studies as Topic; Neoplasms; Quality of Life; Radiation Tolerance; Recombinant Proteins; Treatment Outcome

Anemia is a frequent complication in cancer, occurring in more than 50% of patients with malignancies. Several factors can cause anemia in these patients, such as blood loss, hemolysis, bone marrow infiltration, hypersplenism, and nutrient deficiencies. However, in a considerable number of patients, no cause other than malignant disease itself can be implicated. This cancer-related anemia is similar to the anemia observed in other chronic diseases, such as rheumatoid arthritis and some chronic infections. The syndrome of anemia of chronic disease is characterized by a hyporegenerative, normocytic, normochromic anemia associated with reduced serum iron and transferrin saturation but elevated (or normal) ferritin levels. Cancer-related anemia results from activation of the immune and inflammatory systems, leading to increased release of tumor necrosis factor, interferon-gamma, and interleukin-1. The cytokine-mediated relative failure of erythropoiesis has been further investigated, and three different mechanisms of action are proposed: (1) impaired iron utilization; (2) suppression of erythroid progenitor cells differentiation; and (3) inadequate erythropoietin production. In addition, the life span of red blood cells is shortened in cancer-related anemia and production cannot compensate sufficiently for the shorter survival time. Administration of recombinant human erythropoietin (r-HuEPO, epoetin alfa) can not only correct inadequate endogenous erythropoietin production, but also can overcome the suppression of erythroid progenitor cells and impairment of iron mobilization.

Topics: Anemia; Erythropoiesis; Erythropoietin; Hemoglobins; Humans; Neoplasms

Acute or chronic anemia, a common complication in cancer patients, is associated with the development of tumor hypoxia. It has been shown in several trials that decreased hemoglobin (Hb) levels inducing tumor hypoxia adversely impact radiotherapy or combined radiochemotherapy outcome. For example, pre- and post-treatment Hb levels can be predictive factors for the outcome of radiotherapy, locoregional tumor control, and survival. Two strategies have been established to correct cancer-related anemia and improve radiotherapy outcome: immediate increase of Hb levels with transfusions, or treatment with recombinant human erythropoietin (r-HuEPO, epoetin alfa), which slowly but steadily increases Hb levels to within normal range. As transfusions are associated with severe risks and adverse events, the use of epoetin alfa to treat pre-existing anemia or prevent therapy-induced anemia represents an attractive strategy. The ability of epoetin alfa to maintain or to increase Hb levels in patients undergoing radiotherapy or radiochemotherapy have been shown in several studies in different tumor types. In addition to improving the results of radiotherapy and radiochemotherapy, anemia intervention with epoetin alfa may impact overall survival.

Topics: Anemia; Cell Hypoxia; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Prognosis; Recombinant Proteins

Clinical trials and surveys have shown that a majority of patients with cancer have low hemoglobin levels as a result of the disease and/or treatment. Clinical trials also have shown that the impact of anemia may be more insidious and far-reaching than generally appreciated. Specifically, studies have shown that low hemoglobin levels have significant impact on treatment outcomes, including survival. The mechanisms by which treatment efficacy and survival are compromised have not been fully elucidated but may include cellular compromise (eg, impaired tumor oxygenation), or more general patient compromise (eg, decreased quality of life and treatment delivery). Recent studies have suggested that increasing hemoglobin levels with recombinant human erythropoietin (r-HuEPO, epoetin alfa) have resulted in better outcomes following radiotherapy, chemotherapy, and the combined-treatment modality.

Topics: Anemia; Cell Hypoxia; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Neoplasms; Recombinant Proteins; Treatment Outcome

Recombinant human erythropoietin (r-HuEPO, epoetin alfa) is used for treatment of anemia associated with chemotherapy for non-myeloid malignancies, chronic renal failure and zidovudine treatment in patients infected with the human immunodeficiency virus and for anemic patients undergoing elective, noncardiac, nonvascular surgery. Epoetin alfa has been shown to safely increase preoperative hemoglobin (Hb) levels in anemic patients undergoing elective noncardiac, nonvascular surgery and is more effective than preoperative autologous blood donation in reducing the need for perioperative blood transfusions in orthopedic surgery patients. Epoetin alfa was shown to significantly increase Hb levels and decrease transfusion requirements in gynecologic cancer patients undergoing chemotherapy. A once-weekly regimen of 40,000 IU per dose was effective in these patients. In addition to decreasing transfusion requirements and increasing Hb, epoetin alfa for relieving anemia-related fatigue and improving quality of life was demonstrated in clinical trials in anemic cancer patients receiving chemotherapy. With regard to quality of life in orthopedic surgery patients, a novel instrument to measure the effect of Hb management on postoperative recuperative power (i.e., vigor, functional ability) has been validated and may prove to be useful in optimizing rehabilitation and discharge planning. Extensive clinical experience with epoetin alfa in anemic patients undergoing major elective orthopedic surgery or those with gynecologic cancer provides a strong basis for its use in gynecologic surgery.

Topics: Anemia; Blood Transfusion; Elective Surgical Procedures; Epoetin Alfa; Erythropoietin; Fatigue; Female; Gynecologic Surgical Procedures; Hematinics; Hemoglobins; Humans; Neoplasms; Orthopedics; Quality of Life; Recombinant Proteins; Safety; Treatment Outcome

The liver plays an important role in the production of haemopoietic hormones. It acts as the primary site of synthesis of erythropoietin (EPO) in the fetal stage, and it is the predominant thrombopoietin (TPO)-producing organ for life. In contrast to that of EPO and other liver proteins, the hepatic synthesis of TPO is influenced little by external signals. Hepatocytes express the TPO gene in a constitutive way, i.e. irrespective of the level of platelets in blood. Megakaryocytes and platelets remove the hormone from blood by means of their high-affinity TPO receptors. Normally, the plasma level of TPO is relatively low ( approximately 10(-12) mol/l). However, in thrombocytopenic states due to marrow failure or bleeding, the concentration of circulating TPO may increase greatly. The simple feedback regulation by TPO and its target cells is efficient in maintaining constant platelet numbers in healthy people. Persisting thrombocytopenia develops only in severe liver or marrow failure. On the other hand, an increase in circulating TPO and interleukin 6 (IL-6) may cause reactive thrombocytosis in inflammatory diseases, including cancer. The indications for recombinant human thrombopoietin (rHuTPO) therapy and its impact on transfusion medicine are still under investigation.

Topics: Animals; Clinical Trials as Topic; Erythropoietin; Hematopoiesis; Hormone Replacement Therapy; Humans; Liver; Liver Diseases; Neoplasms; Recombinant Proteins; Thrombocytopenia; Thrombocytosis; Thrombopoietin

Epoetin treatment offers an attractive but costly alternative to red blood cell transfusion for managing anemia associated with cancer therapy. The goal of this review is to facilitate more efficient use of epoetin by 1) quantifying the effects of epoetin on the likelihood of transfusion and on quality of life in patients with cancer treatment-related anemia and 2) evaluating whether outcomes are superior when epoetin treatment is initiated at higher hemoglobin thresholds. Two independent reviewers followed a prospective protocol for identifying studies. Outcomes data were combined with the use of a random-effects meta-analysis model. Double-blind, randomized, controlled trials that minimized patient exclusions were defined as higher quality for sensitivity analysis; randomized but unblinded trials and trials with excessive exclusions were included in the meta-analysis but were defined as lower quality. Twenty-two trials (n = 1927) met inclusion criteria, and 12 (n = 1390) could be combined for estimation of odds of transfusion. Epoetin decreased the percentage of patients transfused by 9%-45% in adults with mean baseline hemoglobin concentrations of 10 g/dL or less (seven trials; n = 1080), by 7%-47% in those with hemoglobin concentrations greater than 10 g/dL but less than 12 g/dL (seven trials; n = 431), and by 7%-39% in those with hemoglobin concentrations of 12 g/dL or higher (five trials; n = 308). In sensitivity analysis, the combined odds ratio for transfusion in epoetin-treated patients as compared with controls was 0.45 (95% confidence interval [CI] = 0.33 to 0.62) in higher quality studies and 0.14 (95% CI = 0.06 to 0.31) in lower quality studies. The number of patients needed to treat to prevent one transfusion is 4.4 for all studies, 5.2 for higher quality studies, and 2.6 for lower quality studies. Only studies with mean baseline hemoglobin concentrations of 10 g/dL or less reported statistically significant effects of epoetin treatment on quality of life; quality-of-life data were insufficient for meta-analysis. No studies addressed epoetin's effects on anemia-related symptoms. We conclude that epoetin reduces the odds of transfusion for cancer patients undergoing therapy. Evidence is insufficient to determine whether initiating epoetin earlier spares more patients from transfusion or results in better quality of life than waiting until hemoglobin concentrations decline to nearly 10 g/dL.

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Controlled Clinical Trials as Topic; Erythropoietin; Hematinics; Humans; Neoplasms; Odds Ratio; Quality of Life; Radiotherapy; Research Design; Sensitivity and Specificity

In the postgenome era, development of novel targeted therapeutics is anticipated to accelerate, with the promise of specifically tailored strategies to treat specific molecularly characterized disease entities. Greater understanding of disease pathophysiology and pharmacologic actions at the molecular, cellular, and tissue levels have provided the basis for expanding the clinical application of available therapies such as recombinant human erythropoietin (r-HuEPO, epoetin alfa). The role of epoetin alfa in anemic cancer patients receiving chemotherapy has grown as our understanding of the relationship between anemia and quality of life in this patient population has evolved. With anemia and tumor hypoxia associated with poorer outcomes in various solid tumors, the potential impact of epoetin alfa on outcomes, as well as quality of life, in patients undergoing radiation or chemoradiation is of considerable interest. Anemia occurs almost universally in critically ill patients, resulting in substantial transfusion requirements. In this setting, the anemia appears to be consistent with anemia of chronic inflammatory disease and is potentially treatable by epoetin alfa. Recent preclinical studies indicate that erythropoietin exhibits neuroprotective effects in models of central nervous system injury, suggesting additional potential novel clinical applications for epoetin alfa worthy of careful investigation. Advances in the understanding of the ras genes and their functional proteins in signaling pathways involved in the development of cancer, particularly hematologic malignancies, over the last decade have prompted development of a new class of agents, farnesyl protein transferase inhibitors (FTIs), designed specifically to inhibit the initial step in Ras protein activation. Initial clinical evaluation of FTIs is ongoing, and preliminary results demonstrate antitumor activity in hematologic malignancies. Further identification and understanding of the function and complex interactions of proteins involved in diseases holds the promise of targeted therapies and improved patient outcomes.

Topics: Alkyl and Aryl Transferases; Anemia; Enzyme Inhibitors; Erythropoietin; Farnesyltranstransferase; Humans; Neoplasms; Quinolones; Recombinant Proteins

Erythropoietin (EPO) is an endogenous hormone produced in the kidney that regulates red blood cell production within the body. Since the cloning and first clinical introduction of recombinant erythropoietin (epoetin) in the late 1980s indications and usage of epoetin have expanded significantly. It is estimated that as many as one third of patients with substantial anemia (hemoglobin less than 10.0 g/dL) resulting from chemotherapy for cancer are treated with epoetin. Though use of epoetin may avoid the inconvenience and infectious risk of blood transfusions, it is expensive and its benefit in some clinical scenarios has been modest. Like many new technologies, strong evidence suggesting situations where the benefit is high has lagged behind its adoption by patients and practitioners. As well, epoetin is expensive and third party payers do not always reimburse it. Research suggests there is considerable variation in epoetin usage in practice. To provide guidance to hematology/oncology specialists regarding use of epoetin, the American Society of Hematology (ASH) and the American Society of Clinical Oncology (ASCO) proposed that the Agency for Healthcare Research and Quality (AHRQ) fund an evidence review by one of the Evidence-based Practice Centers (EPC) that would be used to develop evidence-based guidelines for members of the society. This review highlights principles of evidence-based medicine, distills and appraises the evidence in the published literature that supports the use of epoetin, and presents evidence-based recommendations for use of epoetin in situations where benefit is substantiated by high-quality studies. As well, this review addresses some of the difficulties of performing clinical research in this area, provocative research findings that will require further study, and suggestions regarding epoetin in those areas where further strong evidence has yet to be developed.

Topics: Anemia; Controlled Clinical Trials as Topic; Erythropoietin; Evidence-Based Medicine; Humans; Neoplasms; Practice Guidelines as Topic; Recombinant Proteins; Treatment Outcome; United States; United States Agency for Healthcare Research and Quality

Regulation of the growth and metabolism of large organisms is tightly constrained by the need for precise oxygen homeostasis. Work on control of the haematopoietic growth factor erythropoietin has led to the recognition of a widespread transcriptional response to hypoxia which provides insights into how this is achieved. The central mediator of this response is a DNA binding complex termed hypoxia inducible factor 1 (HIF-1), which plays a key role in the regulation by oxygen of a large and rapidly growing panel of genes. In cancer, activity of the HIF system is up-regulated both by microenvironmental hypoxia and by genetic changes. The clearest example of genetic activation is seen in the hereditary cancer syndrome von Hippel-Lindau (VHL) disease. In normal cells the product of the VHL tumour suppressor gene targets the regulatory HIF subunits (HIF-1alpha and HIF-2alpha) for oxygen-dependent proteolysis, acting as the substrate recognition component of an E3 ubiquitin ligase. In pVHL defective cells this process is blocked leading to constitutive up-regulation of HIF-1alpha subunits, activation of the HIF complex and overexpression of HIF target genes. Using gene array screens we have defined a large number of VHL-regulated genes. The majority of these show hypoxia-inducible responses, supporting the central involvement of pVHL in gene regulation by oxygen. In addition to known HIF target genes involved in angiogenesis, glucose metabolism and vasomotor control, these new targets include examples with functions in matrix metabolism, apoptosis, carbon dioxide metabolism and secondary cascades of transcriptional control. Thus activation of HIF provides insights into the classical metabolic alterations in cancer cells, and into the mechanisms by which microenvironmental hypoxia might influence tumour behaviour. In the case of VHL disease, this activation can be linked to mutations in a defined tumour suppressor gene. Equally regulation of the HIF-1alpha/pVHL interaction in normal cells should provide insights into the physiological mechanisms operating in cellular oxygen sensing.

Topics: Basic Helix-Loop-Helix Transcription Factors; Cell Hypoxia; DNA-Binding Proteins; Erythropoietin; Extracellular Space; Gene Expression Regulation, Neoplastic; Helix-Loop-Helix Motifs; Humans; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Neoplasms; Nuclear Proteins; Trans-Activators; Transcription Factors; von Hippel-Lindau Disease

Anemia is a common cause of cancer-related fatigue. A systematic review of the literature was performed to establish guidelines on the use of epoetin alfa for the treatment of anemia. The evidence in support of these guidelines was selected, reviewed, and summarized by the members of the Canadian Cancer and Anemia Guidelines Development Group. The effects of epoetin alfa on quality of life (QOL) in patients with cancer were examined in 5 randomized, placebo-controlled trials and 2 large, open-label, nonrandomized, community-based studies. The effects of epoetin alfa on red blood cell transfusion requirements were examined in 19 randomized controlled trials (RCTs) with 21 comparisons. All trials compared epoetin alfa to a suitable control group, examined specified outcome measures that could be analyzed, and studied patients with cancer who were receiving chemotherapy. Trials involving patients with hematologic malignancies originating in the bone marrow were excluded. Outcome measures included 1) quality of life (QOL) (as measured by scales including the Linear Analogue Self-Assessment [LASA] and the Functional Assessment of Cancer Therapy [FACT] subscales), and 2) transfusion requirements (as measured by the proportion of patients requiring transfusion and amount of transfusion). The analysis confirmed that epoetin alfa produced statistically significant and clinically relevant improvements in QOL in patients with cancer. The overall relative risk ratio for transfusion among patients receiving epoetin alfa was calculated to be 0.60 (95% Cl, 0.53-0.69; P < 0.00001), representing a 40% reduction in the proportion of patients requiring transfusion. These results support recommendations for the use of epoetin alfa in patients with cancer-related anemia.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Evidence-Based Medicine; Humans; Neoplasms; Practice Guidelines as Topic; Recombinant Proteins

Topics: Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Neoplasms; Recombinant Proteins

Anemia is a frequent complication of cancer and its associated treatment. Although its occurrence is well documented in the chemotherapy setting, the prevalence and nature of anemia in the radiation oncology setting have been inadequately characterized. Preliminary findings from an ongoing retrospective study at Beth Israel Medical Center in New York indicate that mild-to-moderate anemia (ie, hemoglobin levels of 10 to 12 g/dL) is common at presentation for radiation therapy and increases in prevalence and severity during the course of radiation treatment. The symptoms of mild-to-moderate anemia, particularly fatigue, can substantially impair the quality of life of cancer patients. Furthermore, an extensive body of literature has documented an association between low hemoglobin levels and poor locoregional tumor control and survival following curative-intent radiation therapy. Greater efforts by radiation oncologists to document and treat anemia in patients undergoing radiation therapy may provide an opportunity to improve postradiation outcomes and well-being.

Topics: Anemia; Erythropoietin; Hemoglobins; Humans; Neoplasms; Prognosis; Quality of Life; Radiation Oncology; Radiotherapy

Exhaustion and tiredness are frequent symptoms in cancer patients. They are caused by the tumour itself and by application of chemotherapy, surgery, radiation or cytokine treatment. Exhaustion and tiredness are not a consequence of lacking sleep or exaggerated physical or mental labour, but are due to several other factors: Anemia, tumour cachexia, toxicity of chemo- and radiation treatment probably are the most decisive factors for the development of exhaustion and tiredness. As both were taken as inevitable side-effects of cancer and cancer treatment in the past, only little attention has been paid to exhaustion and tiredness and limited research has been done. Among several validated questionnaires measuring quality of life in tumour patients the FACT-An (Functional Assessment of Cancer Treatment--Anemia) and EORTC QLQ-C30 questionnaire are the most well-known for identifying exhaustion and tiredness. Nevertheless, until today there is no mere exhaustion scale exclusively dealing with the problem of exhaustion and tiredness. According to the 10th revision of the International Classification of Diseases (ICD) exhaustion and tiredness are subsumed under the diagnosis of tumour fatigue. In contrast to tumour fatigue, which comprises physical, mental and emotional dimensions, exhaustion and tiredness primarily refer to physical symptoms: Lacking resilience for activities of daily life, day sleepiness and nocturnal insomnia as well as restricted power of concentration are the mainstays of exhaustion and tiredness. However, regarding lacking interests, diminished energy and reduced mental capacity, exhaustion and fatigue partly overlap. From a therapeutic point of view behavioural interventions and drug therapy have successfully been tried. Beside physical exercise and psychostimulants application of Erythropoietin represents an innovative treatment of exhaustion and tiredness.

Topics: Clinical Trials as Topic; Combined Modality Therapy; Erythropoietin; Fatigue; Humans; Leukemia; Neoplasms; Palliative Care; Quality of Life; Recombinant Proteins

Anaemia is a common complication of cancer. The incidence is variable and depends on several factors. A linear correlation between haemoglobin levels and quality of life (QOL) parameters has been found. Erythropoiesis is a finely regulated responsive process and erythropoietin (EPO) is the most important factor influencing progenitor cell proliferation. Impaired EPO production is mediated by inflammatory cytokines liberated in cancer patients. For this reason, EPO has been proposed as an alternative to blood transfusions, which involve many hazards. EPO treatment has been found to be effective in preventing anaemia and reducing the need for blood transfusions, although it would be useful to identify high-risk patient subgroups who would benefit most from this expensive treatment.

Topics: Anemia; Blood Transfusion; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Recombinant hematopoietic growth factors were introduced into clinical practice a decade ago: erythropoietin in 1989, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in 1991, and interleukin-11 in 1997. The role of these agents in supportive therapy for children with cancer is still under considerable evaluation. This pediatric-based review summarizes current clinical applications, practice guidelines, and practice patterns for hematopoietic growth factors in the supportive care of children with cancer. It also discusses ongoing controversies and unanswered questions.

Topics: Chemotherapy, Adjuvant; Child; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; Humans; Neoplasms; Neutropenia

The therapeutic potential of erythropoietin gains increasing attention among radiation oncologists because the prognosis is better for patients with high blood hemoglobin levels following radiotherapy. However, there is still a debate on how hemoglobin affects radiotherapy. Further, the means to manipulate the hemoglobin level, their indication and administration need to be clarified. Available experimental and clinical data on hypoxia, anemia and on their treatment with erythropoietin have been extensively discussed at an international conference in Freiburg, Germany, in June 1999. This report gives a summary reviewing the topic.

Topics: Anemia; Animals; Cell Hypoxia; Erythropoietin; Hemoglobins; Humans; Neoplasms; Neoplasms, Experimental; Quality of Life; Time Factors; Treatment Outcome

Topics: Adult; Anemia; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins

Topics: Anemia; Erythropoietin; Humans; Immunosuppression Therapy; Neoplasms; Recombinant Proteins

Anemia is a common complication of cancer but its causes differ widely. However, a significant number of patients with even early cancer experience a suppression of the action of erythropoietin on the bone marrow, presumably caused by the release of cytokines. The ensuing anemia may be mild and "asymptomatic". Nevertheless, it drains physical and emotional vigor so necessary in the fight against the underlying disorder. The therapeutic use of recombinant human erythropoietin has been gratifying and in many cases restored to near normal not only the hemoglobin concentration but also the quality of life.

Topics: Anemia; Erythroblasts; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Anaemia in cancer patients is multifactorial and may occur as a either a direct effect of the cancer, as a result of the cancer treatment itself, or due to chemical factors produced by the cancer. The clinical symptoms of anaemia vary according to the individual's capacity to respond to blood loss or reduced red cell production. The haematological features in anaemic patients depend on the different types of malignant disease. Clinical and laboratory evaluation, and examination of the bone marrow can provide important diagnostic clues in many cases. Decisions are commonly made based on subjective consideration rather than on objective data. Blood transfusion involves many hazards, some of which may be reduced or avoided. Erythropoietin (EPO) treatment has been found to be effective in preventing anaemia and in reducing the need for blood transfusions, although it would be useful to identify high-risk patient subgroups who would benefit most from this expensive treatment. In advanced cancer patients the use of blood transfusion should be evaluated on an individual basis, according to the presence of distressing symptoms and life expectancy. These measures are unlikely to have an effect in irreversible and progressive bleeding states.

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Bone Marrow Neoplasms; Erythropoiesis; Erythropoietin; Humans; Neoplasms; Radiotherapy

Topics: Anemia; Antineoplastic Agents; Blood Transfusion, Autologous; Erythropoietin; Humans; Kidney Failure, Chronic; Neoplasms; Renal Dialysis

Anemia is frequent and significantly adds to the morbidity of cancer patients, and has been associated with decreased quality of life (QOL). Three open-label community-based studies of epoetin alfa in cancer-related anemia (two using three-times-weekly dosing and one using once-weekly dosing) in more than 7,000 patients have been performed. Results indicate that epoetin alfa treatment significantly increases hemoglobin and reduces transfusion requirements by 8 to 12 weeks, and using quality assessment tools, it has been shown to be associated with improvement in QOL scores. Incremental analysis demonstrated that the greatest improvement in QOL outcomes was associated with an increase in hemoglobin level from 11 g/dL to 12 g/dL (range, 11 to 13 g/dL). Strategies for management of anemia may need to take into account the possible advantage of early intervention in improving functional status in cancer patients.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Anaemia is a common and debilitating feature of malignancy that negatively impacts quality of life (QoL). QoL is multidimensional, usually comprising physical, emotional, social and cognitive functioning, although it may be supplemented with more specific aspects of wellbeing. QoL is also a highly subjective dynamic parameter, in that it changes as a function of time and conditions. For meaningful interpretation of results, therefore, the components of QoL and conditions must be listed and standardised. Existing guidelines should be followed on when QoL is a valid parameter to include in a trial design and which QoL instrument to use. General scales that can be customised, such as the European Organization for Research and Treatment of Cancer (EORTC) and Functional Assessment of Cancer Therapy-General (FACT-G) instruments, are recommended. QoL should be assessed at least three times over the course of a study, with lower frequencies of assessment and simple assessment methods being key to compliance. Studies assessing the effect of recombinant human erythropoietin (rHuEPO) on anaemia and QoL have used various QoL instruments but agree that there is a positive correlation between haemoglobin value and QoL. When QoL assessment is correctly carried out, it can supplement standard endpoints, such as survival and response, and lead to more informed decisions concerning cost:benefit ratios.

Topics: Anemia; Clinical Trials as Topic; Erythropoietin; Health Status; Humans; Mental Health; Neoplasms; Quality of Life; Recombinant Proteins; Surveys and Questionnaires; Treatment Outcome

One of the goals of the proposed National Comprehensive Cancer Network Practice Guidelines for Cancer-Related Fatigue is outlining a systematic approach to the evaluation, intervention, and assessment of outcome in the treatment of fatigue. Anemia has been characterized as a major contributor to fatigue, and a review of patients receiving cancer therapy showed that the majority developed anemia. The current data support the value of returning hemoglobin levels to the normal range in terms of maximizing improvements in quality of life related to anemia. The potential impact of anemia in terms of treatment outcome is under investigation.

Topics: Anemia; Clinical Trials as Topic; Erythropoietin; Fatigue; Female; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Risk Factors

Topics: Combined Modality Therapy; Erythropoietin; Humans; Neoplasms; Radiotherapy; Recombinant Proteins

Recombinant human erythropoietin (Epoetin alfa) is effective in increasing hemoglobin concentration and hematocrit, and in significantly reducing transfusion requirements in the majority of patients with either the anemia of chronic renal failure or chemotherapy-induced anemia of cancer. Identification of factors that could enable the clinician to predict individual patient hematological responses to Epoetin alfa therapy would be of great value. Changes in levels of serum transferrin receptor protein, hemoglobin, ferritin and reticulocyte count, following a short course of Epoetin alfa therapy, were useful markers for predicting later hematopoietic responses to Epoetin alfa. In addition, recent data suggest that low baseline erythropoietin levels, in association with increases of either >0.5 g/dl in hemoglobin or >/=25% in circulating levels of transferrin receptor protein after 2 weeks of Epoetin alfa therapy, are highly predictive of a response (>/=2 g/dl increase in hemoglobin) to Epoetin alfa. Progress has clearly been made in the development of predictive models that can identify those patients most likely to respond to Epoetin alfa by monitoring several specific hematological parameters at baseline and early in therapy. Future studies will focus on nonhematological measures of response, such as transfusion requirement and quality of life benefit.

Topics: Anemia; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematinics; Hematopoiesis; Humans; Neoplasms; Predictive Value of Tests; Recombinant Proteins; Treatment Outcome

The prevalence of anaemia in patients with cancer lies between 10 and 40%, depending on the type of tumor and chemotherapy. Anaemia has a significant impact on the quality of life, along with pain or disease progression. There are multiple causes but the physiopathology resembles that of inflammatory anaemia. The following mechanisms can be distinguished: a resistance of the erythroid precursor cells (BFU-e, CFU-e) to erythropoietin, an inappropriately decreased renal erythropoietin secretion for a given haemoglobin value and alterations of the iron metabolism leading to a functional iron deficiency. Recombinant human erythropoietin (r-hu-EPO) is safe and efficient in the treatment of anaemia of chronic renal failure and rheumatoid arthritis. In oncology different phase I and II studies have demonstrated an efficacy (increase of haemoglobin, decrease of transfusion requirements) in about 50% of all adult patients. A response to a subcutaneous r-hu-EPO treatment with a relatively high posology of 150 U/kg three times a week can be expected after one to two months. No single reliable parameter will predict a response to the r-hu-EPO treatment. Several phase III studies confirm that anaemia in cancer patients undergoing chemotherapy (notably with cisplatin) can be corrected in 40 to 60% of all cases and that the haemoglobin increase improves the quality of life. Finally, recent clinical trials suggest that an early r-hu-EPO treatment might prevent the occurrence of anaemia secondary to chemotherapy. Several parameters will have to be specified such as the precise definition of the groups at risk, the appropriate haemoglobin level to initiate a r-hu-EPO treatment, its optimal posology, as well as the role of the iron substitution and its route of administration. The impact of the r-hu-EPO treatment on the quality of life of cancer patients constitutes a priority for future studies, which will have define the exact role of r-hu-EPO in oncology management.

Topics: Adult; Anemia; Clinical Trials as Topic; Erythropoietin; Humans; Neoplasms; Recombinant Proteins; Treatment Outcome

Anemia in cancer patients has many etiologies. Iron therapy clearly is indicated in patients whose anemias are associated with iron deficiency. However, a frequent cause of anemia in cancer is the "anemia of chronic disorders," in which, although functional iron may be low, tissue iron remains normal or high. Administration of iron with erythropoietin to such patients requires careful and frequent evaluation of hematologic and iron values. Inadvertent iron loading can contribute to deterioration of a variety of organ systems, as well as to increased proliferation of neoplastic cells.

Topics: Anemia; Erythropoietin; Humans; Iron; Iron Overload; Neoplasms; Recombinant Proteins

Approximately 50% of cancer patients develop anemia. In the past, the only available treatment option for these patients was transfusion. Since the late 1980s, recombinant human erythropoietin (rHuEPO, epoetin alfa [Epogen, Procrit]) has provided a treatment alternative. Controlled clinical trials have shown that rHuEPO increases hemoglobin and hematocrit levels and reduces the need for transfusions in patients with cancer-related anemia. These controlled trials have suggested (as larger, uncontrolled studies) that the improvements in hemoglobin are associated with increases in energy level, functional status, and overall quality of life. However, only about 50% of patients respond adequately to usual doses of rHuEPO. In the chronic renal failure population, functional iron deficiency is the most common cause of inadequate response to rHuEPO. It has been hypothesized that functional iron deficiency may also occur in cancer patients receiving rHuEPO and may account for the lack of response in up to half of those patients. Studies in renal failure patients have shown that administration of intravenous iron can correct functional iron deficiency more effectively than oral iron and may improve response to rHuEPO. Intravenous iron also reduces the total amount of rHuEPO needed to normalize hematocrit and hemoglobin levels, thereby reducing treatment costs. Ongoing clinical trials are evaluating whether IV iron can also improve rHuEPO responsiveness in patients with cancer-related anemia.

Topics: Anemia; Erythropoietin; Health Care Costs; Hematocrit; Hemoglobins; Humans; Iron; Iron Deficiencies; Kidney Failure, Chronic; Neoplasms; Recombinant Proteins

Cancer-related anaemia has a number of causes, not least the underlying malignancy itself which plays a role in suppressing erythropoiesis. Anaemia is often exacerbated by cancer treatments, in particular routinely used cytotoxic chemotherapy. Chronic anaemia of cancer is often characterized by inappropriately low levels of endogenous erythropoietin for the degree of anaemia, and manifests clinically with generalized hypoxia and resultant severe fatigue. Epoetin alfa is one recombinant form of erythropoietin, the primary human growth factor responsible for promoting proliferation and survival of erythroid progenitor cells. Epoetin alfa has been widely studied for the treatment of anaemia associated with renal failure and is now recognized as having significant potential in the management of cancer-related anaemia. Studies suggest that epoetin alfa is an effective treatment in a proportion of cancer patients with symptomatic anaemia. It also appears useful for the prevention of chemotherapy-induced anaemia. Studies in a number of different cancer settings have shown that epoetin alfa significantly increases haemoglobin and haematocrit, reduces transfusion requirements and improves quality of life for the patient.

Topics: Anemia; Erythropoietin; Humans; Neoplasms

Anemia, a decreased oxygen-carrying capacity of the blood, develops frequently in patients with end-stage renal disease (ESRD) or cancer. Given the wide variation in clinical response to erythropoietin in the treatment of anemia associated with these diseases, 2 meta-analyses of its effectiveness were undertaken. Databases (MEDLINE and International Pharmaceutical Abstracts) were searched to identify relevant articles. Search terms included erythropoietin, anemia, end-stage renal disease, cancer, multiple myeloma, and myelodysplastic syndrome. Searches were limited to human subjects and the English language. Reference lists of identified articles were reviewed for further articles of interest. The primary author (W.A.M.) selected the articles, and 2 researchers, working independently, extracted the necessary data. Articles had to meet the following criteria to be included in the meta-analyses: (1) Articles must have dealt with treatment of subjects with documented anemia. (2) Studies must have been original research with sample size > or =10. (3) Abstracts could be included if the full research manuscript was unavailable. (4) Patients could not be concurrently receiving other growth factors. (5) The quality of the selected articles must have been assessed by 2 independent researchers. A clinical response to erythropoietin was defined as a 0.06 increase in hematocrit or a 20 g/L increase in hemoglobin. Thirty-nine of the 76 identified articles were included in the meta-analyses. The effectiveness of erythropoietin was calculated at 87% for ESRD, 79% for multiple myeloma, 40% for solid tumor cancer, and 13% for myelodysplastic syndrome. Both subgroup and sensitivity analyses were performed.

Topics: Anemia; Clinical Trials as Topic; Erythropoietin; Humans; Kidney Failure, Chronic; Neoplasms

Anemia is a common complication of myelosuppressive chemotherapy that results in a decreased functional capacity and quality of life (QOL) for cancer patients. Severe anemia is treated with red blood cell transfusions, but mild-to-moderate anemia in patients receiving chemotherapy has traditionally been managed conservatively on the basis of the perception that it was clinically unimportant. This practice has been reflected in the relative inattention to standardized and complete reporting of all degrees of chemotherapy-induced anemia. We undertook a comprehensive review of published chemotherapy trials of the most common single agents and combination chemotherapy regimens, including the new generation of chemotherapeutic agents, used in the treatment of the major nonmyeloid malignancies in adults to characterize and to document the incidence and severity of chemotherapy-induced anemia. Despite identified limitations in the grading and reporting of treatment-related anemia, the results confirm a relatively high incidence of mild-to-moderate anemia. Recent advances in assessing the relationships of anemia, fatigue, and QOL in cancer patients are providing new insights into these closely related factors. Clinical data are emerging that suggest that mild-to-moderate chemotherapy-induced anemia results in a perceptible reduction in a patient's energy level and QOL. Future research may lead to new classifications of chemotherapy-induced anemia that can guide therapeutic interventions on the basis of outcomes and hemoglobin levels. Perceptions by oncologists and patients that lesser degrees of anemia must be endured without treatment may be overcome as greater emphasis is placed on the QOL of the oncology patient and as research provides further insights into the relationships between hemoglobin levels, patient well-being, and symptoms.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Clinical Trials as Topic; Colorectal Neoplasms; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Head and Neck Neoplasms; Hematinics; Humans; Incidence; Lung Neoplasms; Lymphoma; Middle Aged; Neoplasms; Ovarian Neoplasms; Recombinant Proteins; Severity of Illness Index; Treatment Outcome

To measure the cost effectiveness of a supportive care intervention when the no-treatment option is unrealistic in an analysis of recombinant human erythropoietin (epoetin) treatment for anaemic patients with cancer undergoing chemotherapy. Further, to assess whether quality-adjusted life-years (QALYs) can provide the basis for an appropriate measure of the value of supportive care interventions.. A modelling study drawing cost and effectiveness assumptions from a literature review and from 3 US clinical trials involving more than 4500 patients with cancer who were treated with chemotherapy, radiotherapy, epoetin and blood transfusions as needed under standard care for patients with cancer.. When compared with transfusions, epoetin is cost effective under varying assumptions, whether effectiveness is measured by haemoglobin level or quality of life. Specifically, under a base-case scenario, the effectiveness resulting from $US1 spent on standard care can be achieved with only $US0.81 of epoetin care. Due in part to the health-state dependence of the significance patients attach to incremental changes in their responses on the linear analogue scale, cost per QALY results are ambiguous in this supportive care context.. Under a broad range of plausible assumptions, epoetin can be used cost effectively in the treatment of anaemic patients with cancer. Further, QALYs have limited applicability here because, as a short term supportive treatment, epoetin enhances the quality but not the length of life. Future research would benefit from the establishment of consistent values for quality-of-life changes across patients and health status, and the extension of the QALY framework to supportive care.

Topics: Anemia; Combined Modality Therapy; Cost-Benefit Analysis; Erythropoietin; Humans; Neoplasms; Pain Measurement; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Recombinant Proteins

Hematopoietic growth factors have made a significant impact on the treatment of cancer, primarily in the prevention of infections associated with chemotherapy-induced neutropenia, in progenitor cell transplantation, in chemotherapy-induced thrombocytopenia, and in chemotherapy-induced anemia. As seen with this review, our basic understanding of hematopoietic growth factors and their clinical potential continue to expand. Work will need to continue, especially with the new thrombopoietic factors, megakaryocyte growth and developing factor, thrombopoietin, and IL-11, to fully categorize their biology and clinical characteristics.

Topics: Amifostine; Animals; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; Humans; Interleukin-11; Neoplasms; Stem Cell Factor

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Erythropoietin; Humans; Neoplasms; Recombinant Proteins; Treatment Outcome

Recombinant human erythropoietin (EPO; epoetin) has been shown to be effective in improving anemia in a proportion of cancer patients. The response rate is approximately 60%, but varies considerably according to baseline hematocrit and transfusion needs, as well as the response criteria used. Response is not greatly influenced by the type of tumor, except in situations of major marrow involvement and limited residual hematopoiesis, or in the presence of specific mechanisms of anemia, such as hemolysis, splenomegaly, bleeding, hemodilution, or ineffective erythropoiesis. Stem cell damage by previous therapy as well as marrow suppression by current intensive chemotherapy can impair response. Besides its intensity, the type of chemotherapy may not be critical, although patients undergoing platinum-based chemotherapy may respond faster than those receiving non-platinum regimens. Complications, such as infections, bleeding, or nutritional deficiencies, may have a major negative impact on outcome. An important response-limiting factor is functional iron deficiency (ie, an imbalance between iron needs in the erythropoietic marrow and iron supply), which depends on the level of iron stores and its rate of mobilization. Functional iron deficiency is best monitored by the percentage of hypochromic red blood cells, and oral or intravenous iron supplements should be given when this percentage increases above 10%. All these factors explain why the response rate to epoetin is only approximately 60%. Therefore, it would be interesting to develop models that could help predict response to epoetin to help select the most appropriate cancer patients for this therapy. Few baseline parameters have been shown to be highly predictive of response in patients with solid tumors, although most studies in patients with myeloma or lymphoma have indicated that patients with a low baseline serum EPO level will respond better. Early changes after 2 to 4 weeks of treatment are also of great interest. Among these early changes, increments of soluble transferrin receptor, reticulocytes, and hemoglobin, as well as the persistence of elevated ferritin or EPO levels, have all shown some predictive value. Combination of baseline serum EPO and the 2-week increment of soluble transferrin receptor or hemoglobin may provide the best prediction of response.

Topics: Algorithms; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Models, Biological; Neoplasms; Recombinant Proteins

Patients with cancer have inappropriately low levels of endogenous erythropoietin for the degree of anemia and further suppression of erythropoiesis results from chemotherapy. Patients with lung cancer, in particular, require a high frequency of transfusions, as they are unable to tolerate the symptoms of anemia due to their underlying pulmonary disease and, often, their age. Data from phase I and II trials indicated that epoetin alfa could increase hemoglobin concentration and reduce transfusion requirements. The beneficial response was dose dependent. These findings were confirmed in a series of three double-blind, placebo-controlled, multicenter phase III trials. Clinical trial evidence indicates that 150 IU/kg epoetin alfa three times weekly effectively treats anemia and decreases transfusion requirements in most cancer patients after the first month of chemotherapy. Furthermore, epoetin alfa will reduce the degree of anemia and markedly reduce the need for transfusions, thereby preventing anemia in patients undergoing multiple cycles of platinum-based combination chemotherapy. Epoetin alfa is well tolerated and shows marked activity in preventing anemia and reducing blood transfusion requirements in patients undergoing cyclic chemotherapy.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

First used successfully to correct the anemia associated with chronic renal failure, epoetin alfa has been shown to be highly effective in many patients with either hematologic or nonhematologic malignancies. Multiple studies have demonstrated effective response rates, with increases in hemoglobin concentration and reduction or elimination of transfusion requirements in up to 75% or 80% in such patients. Nevertheless, as clinical experience has grown, several issues have arisen. First, not all cancer patients respond to epoetin alfa and, consequently, it is important to identify those patients most likely to respond to make early clinical decisions regarding dose adjustment or drug withdrawal. Second, experience in patients with renal failure has revealed a state of "functional iron deficiency" and, thus, highlighted the importance of iron supplementation to optimize the response to epoetin alfa. Does "functional iron deficiency" complicate epoetin alfa therapy of patients with the anemia of cancer, and could such patients benefit from iron supplementation? Finally, some hematologic malignancies, especially myelodysplastic syndromes, can be resistant to epoetin alfa monotherapy. Can the effective response rates in such patients be improved by combining epoetin alfa therapy with the administration of other hematopoietic growth factors? Epoetin alfa has made substantial contributions to the care of patients with cancer and, with time, additional uses for this very valuable drug will become apparent.

Topics: Anemia; Blood Transfusion; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Iron; Neoplasms; Quality of Life; Recombinant Proteins

Topics: Anemia; Clinical Trials as Topic; Cost-Benefit Analysis; Erythropoietin; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Research Design; Sweden

Anemia is a frequent complication of cancer and its treatment and can have a significant impact on one's quality of life. The utility of mechanisms currently used to ameliorate the anemia (i.e. transfusion and erythropoietin) is reviewed vis-à-vis improving quality of life.

Topics: Anemia; Blood Transfusion; Clinical Trials as Topic; Erythropoietin; Humans; Neoplasms; Quality of Life

Patients with cancer frequently develop anaemia, due either to the malignant disease itself or to its treatment. Various factors, including the type of malignancy and the type and intensity of chemotherapy, influence the prevalence of anaemia and the need for transfusions. Among patients with solid tumours, those with lung cancer and ovarian cancer are reported to have the highest frequency of anaemia (52% and 51%, respectively) and the highest rate of transfusion requirements (28% and 25%, respectively). Patients with a low level of haemoglobin (Hb) (10-12 g/dl) at the start of chemotherapy are particularly at risk of developing anaemia and requiring transfusions. Similarly, patients treated with platinum-based regimens more often develop anaemia and need transfusions. The frequency of transfusion requirements in these patients can amount to 47%-100%, depending on the cumulative dose of platinum and other risk factors, such as advanced age, loss of body weight before treatment, advanced disease stage, and particularly a low primary level of Hb (11 g/dl) and a decrease in Hb level (1-2 g/dl) after the first cycle of treatment. The causative mechanism of platinum-induced anaemia is reported to be, beside myelosuppression, a deficient production of erythropoietin (EPO) resulting from drug-induced renal tubular damage. In a number of randomised and nonrandomised studies, recombinant human (rh) EPO has been shown to be effective in the treatment of cancer-related anaemia (CRA) and in the prevention and treatment of chemotherapy-induced anaemia. An appropriate dose of rhEPO for the start of treatment is 150 U/kg given subcutaneously three times per week (t.i.w.). The response rate of anaemia ranges from 40% to 85%. rhEPO is well tolerated, but the cost of treatment requires patient selection and parameters predicting response as early as possible after the start of treatment. Appropriate groups of patients for treatment with rhEPO are those with an Hb level of < 10 g/dl and those with a higher Hb level, but symptomatic anaemia. Other groups are patients who are going to receive chemotherapy and have a low primary level of Hb (10-12 g/dl) and patients who receive platinum-based chemotherapy and have experienced a marked decrease in their Hb level (1-2 g/dl) from baseline to the second cycle of treatment. These patients have a high risk of becoming anaemic and requiring transfusions during chemotherapy. In anaemic cancer patients treated with rhEPO, an early ind

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Dose-Response Relationship, Drug; Erythropoietin; Humans; Neoplasms; Patient Selection; Randomized Controlled Trials as Topic; Recombinant Proteins

Topics: Anemia; Erythropoietin; Humans; Neoplasms; Quality of Life; Recombinant Proteins

The anaemia associated with cancer can be effectively treated with recombinant human erythropoietin (rHuEpo) in about 60% of the patients. However, the response rate varies according to treatment modalities as well as the response criteria used. A number of disease- or chemotherapy-related factors determines the probability of response. Several specific mechanisms of anaemia, such as haemolysis, splenomegaly, bleeding, haemodilution, or ineffective erythropoiesis can seriously interfere with response. However, the type of tumor, in particular haematologic versus non-haematologic, is not critical, except in situations of major marrow involvement and limited residual haematopoiesis. Stem cell damage by previous therapy, reflected by low platelet counts or high transfusion needs, will impair response. In addition, marrow suppression by current intensive chemotherapy will also have a negative impact. Besides its intensity, the type of chemotherapy may not be critical, although patients undergoing platinum-based chemotherapy may respond faster than those receiving non-platinum regimens. Complications such as infections, bleeding or nutritional deficiencies may have a major negative impact on outcome. An important response-limiting factor is functional iron deficiency, i.e. an imbalance between iron needs in the erythropoietic marrow and iron supply, which depends on the level of iron stores and its rate of mobilisation. Therefore, oral or preferably intravenous iron supplements should be given when serum ferritin is below 40-100 micrograms/l, reflecting the absence of iron stores, or when the percentage of hypochromic red cells rises above 10%, indicating functional iron deficiency even in the presence of adequate storage iron. Because up to 40% of the patients will not respond to rHuEpo, it is of utmost importance to develop models that could help predict response to rHuEpo and thus select the most appropriate cancer patients for this therapy. Most studies of patients with myeloma or lymphoma have indicated that patients with a low baseline serum Epo level will respond better, but this is not true of patients with solid tumors. Also of considerable interest are early changes of erythropoietic parameters after 2 to 4 weeks of treatment, including increments of serum transferrin receptor (sTfR), reticulocytes and haemoglobin, as well as the persistence of elevated ferritin or Epo levels. Combination of baseline serum Epo and the 2-week increment of sTfR or haem

Topics: Algorithms; Anemia; Erythropoietin; Humans; Models, Theoretical; Neoplasms; Predictive Value of Tests; Recombinant Proteins; Sensitivity and Specificity; Treatment Outcome

Many patients with solid tumours or haematological malignancies develop anaemia, and the use of chemotherapy aggravates this condition. Red blood cell transfusions are often necessary but are associated with many risks, including immunosuppressive effects that may increase the risk of tumour recurrence. Many clinical studies have shown that epoetin (recombinant human erythropoietin) therapy can ameliorate, or even prevent, the anaemia associated with chemotherapy and cancer (including solid tumours as well as multiple myeloma or lymphoma). Response, defined as a significant (>50%) reduction in the rate of transfusions and/or a significant (>2 g/dl) elevation of haemoglobin levels, is usually observed in about 60% of the patients, irrespective of the type of standard chemotherapy given. The decrease in transfusion requirements is the major objective of epoetin therapy, because they are costly, inconvenient and are associated with potential adverse effects. Epoetin therapy also brings about substantial improvements in various indices of quality of life that are proportional to changes in haemoglobin level. However, large dosages of epoetin are generally required and about 40% of patients do not respond even to very high dosages. A number of adverse effects of epoetin therapy have been observed in patients with renal failure. The most prominent include hypertension, headaches, seizures and thrombotic events. These complications can also occur in patients with renal failure who are not receiving epoetin. Their exact incidence has been assessed in placebo-controlled studies, which have demonstrated that there is no increased risk of thrombosis or seizure with epoetin. However, it is now generally accepted that 10 to 20% of haemodialysis patients will experience an elevation of blood pressure because of epoetin and there is no doubt that a rapid elevation of blood pressure may cause generalised seizures. In other settings, including anaemia associated with cancer, very few adverse effects have been attributed to epoetin. However, close monitoring of blood pressure should be implemented in patients with hypertension. There is no evidence that epoetin stimulates tumour growth. With the dosages of epoetin currently used, there is no evidence of stem cell competition, resulting in thrombocytopenia or neutropenia, or of stem cell exhaustion, producing secondary anaemia when treatment is stopped. Epoetin is a remarkably well tolerated drug that offers significant ben

Topics: Anemia; Animals; Erythropoietin; Humans; Neoplasms; Recombinant Proteins; Risk Assessment

While the production and degradation of erythrocytes are carefully balanced in healthy persons several processes can lead to an imbalance in tumor patients resulting in anemia.. Processes caused by the tumor itself can lead to a typical "anemia of chronic disease" which is normochromic, normocytic, accompanied by both a reduced number of reticulocytes and reduced iron-binding capacity. In many cases, the erythropoietin response to anemia is insufficient. Cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor seem to be involved in suppressing erythropoiesis by acting on the bone marrow and on erythropoietin production. Anemia can also be the result of cancer therapy, as is particularly prominent in patients with lung cancer receiving chemotherapy (incidence of anemia 20 to 50%). PROGNOSTIC FACTOR: Several studies have demonstrated that anemia is not only linked to an impaired quality of life but to prognosis as well. Albain et al. [2] identified a hemoglobin level of below 11 g/dl as a significant independent prognostic factor associated with shorter survival of chemotherapeutically treated non-small cell lung cancer (NSCLC) patients. The same applies to a hemoglobin level below 12.7 g/dl for radiotherapeutically treated NSCLC patients according to a study by Ohlhauser et al. (Oncology 1997;20:1689-92). Several studies have confirmed this prognostic importance of hemoglobin level for other solid tumors.. To correct anemia, clinicians have several options. Given the risks associated with transfusions, especially for tumor patients, recombinant erythropoietin holds promise for raising hemoglobin levels and thereby improving therapeutic efficacy and survival.

Topics: Anemia; Erythropoietin; Hemoglobins; Humans; Neoplasms; Prognosis; Recombinant Proteins

Tumor growth, oxygenation and radiosensitivity were investigated in a series of studies in which anemia was induced in rats either by the development of a hemorrhagic ascites or by a single dose of carboplatin, which resulted in reductions in the hemoglobin concentration of 30%. The development of both the tumor- and chemotherapy-induced forms of anemia could be prevented by the s. c. administration of recombinant human erythropoietin (rhEPO; 1000 IU/kg, 3 times per week over 14 days). Seven days before pO2 measurements, DS-sarcomas were implanted s. c. on the hind foot dorsum. With both anemia models, tumor growth did not differ between anemic animals and animals treated with rhEPO. Tumor oxygenation was measured polarographically using O2-sensitive needle electrodes and pO2 histography. In anemic animals, tumor oxygenation was poorer compared to untreated controls. The reduction could be partially reversed by rhEPO treatment, but not fully compensated. These findings suggested that rhEPO treatment can improve tumor oxygenation by increasing the O2 availability to tumor tissue. Further experiments therefore assessed the possibility of enhancing the efficacy of a single radiation dose (10 Gy) by rhEPO treatment of anemic animals. While anemic animals showed decreased radiosensitivity, prevention of anemia by rhEPO treatment resulted in a significant increase in tumor radiosensitivity, although again a full recovery to radiosensitivity levels found in non-anemic animals was not achieved.

Topics: Anemia; Animals; Erythropoietin; Humans; Neoplasms; Neoplasms, Experimental; Oxygen Consumption; Radiation Tolerance; Recombinant Proteins

Oncologists have several reasons for trying to maintain or increase hemoglobin levels in their patients during therapy. Relief of the symptoms of anemia, including fatigue and dyspnea, are traditional, well-accepted indications. A newer rationale is to enhance the efficacy of radiation therapy and/or chemotherapy in controlling tumors. A laboratory animal study found that administration of recombinant human erythropoietin (rHuEPO) increased intratumoral median oxygen levels and diminished the proportion of measurements in the very low (< 3 mm Hg) range. Hemoglobin level is a strong independent prognostic factor for tumor control by radiation therapy. The hemoglobin level at the end of radiation therapy is a stronger prognostic factor than is the hemoglobin level at the start of therapy. Numerous clinical trials have utilized rHuEPO during radiation with or without concurrent chemotherapy. All 4 trials which enrolled patients with low hemoglobin levels (< 12 to 13.5 g/dl) found that rHuEPO significantly increased hemoglobin within 2 weeks and that hemoglobin levels continued to rise until the end of rHuEPO treatment. rHuEPO was efficacious in limiting the decrease in hemoglobin and use of packed red blood cell transfusion in the one reported trial in which it was used in patients with initially normal hemoglobin levels during intensive concurrent radiation and chemotherapy. One trial found a statistically significant improvement in complete pathologic response rate after neoadjuvant chemoradiotherapy with the use of rHuEPO. rHuEPO has a potentially large to play in the care of the cancer patient.

Topics: Anemia; Clinical Trials as Topic; Erythropoietin; Female; Hemoglobins; Humans; Male; Neoplasms; Recombinant Proteins

The development of the hematopoietic growth-factors had a major influence on the treatment of malignant diseases. Quality of Life gets increasingly important in the setting of high-dose chemotherapy and stem cell transplantation. Granulocyte-colony stimulating factor (G-CSF) and erythropoietin (EPO) are two of the most important hematopoietic growth-factors, which contribute to the amelioration of the complications of the malignant disease and the side-effects of the cytostatic treatment. G-CSF reduces the median time of neutrophil recovery, the rate of severe infections and the length of hospitalization. Erythropoietin has a beneficial impact on the quality of life of cancer patients by improving the chronic anemia of cancer, leading to a higher level of physical and social activity, brighter mood, improvement of appetite and general sense of well-being.

Topics: Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Neoplasms; Quality of Life; Recombinant Proteins

An erythrocytosis describes an increased peripheral blood packed cell volume (PCV) and is deemed to be absolute or apparent depending on whether or not the measured red cell mass (RCM) is above the reference range. This reference range must be related to the individual's height and weight to avoid erroneous interpretations using ml/kg total body weight expressions in obesity. Absolute erythrocytoses are divided into primary, where the erythropoietic compartment is intrinsically abnormal, secondary, where the erythropoietic compartment is normal but is responding to external pathological events leading to an increased erythropoietin drive, and idiopathic, where neither a primary nor a secondary erythrocytosis can be established. Both primary and secondary erythrocytoses have congenital and acquired forms. The only form of primary acquired erythrocytosis that has been defined is the clonal myeloproliferative disorder, polycythaemia vera (PV). Modified diagnostic markers for PV are proposed. Thrombocytoses can be classified into primary, where megakaryopoiesis is intrinsically abnormal, secondary, where megakaryopoiesis is normal but increased platelet production is a reaction to some other unrelated pathology, and finally idiopathic. This latter new group would be used for patients not satisfying the criteria for primary or secondary thrombocytoses, if these were more precise and rigidly used than currently is the case. While theoretically congenital and acquired forms of primary and secondary thrombocytoses might exist, only one cause of secondary congenital thrombocytosis has been established, and primary congenital thrombocytosis has not yet been precisely defined. Primary (essential) thrombocythaemia (PT) is one of the forms of primary acquired thrombocytoses. The diagnostic criteria of PT traditionally involve the exclusion of secondary thrombocytoses and other myeloproliferative disorders but marrow histology could hold a key positive diagnostic role if objective histological features of PT were agreed.

Topics: Anthropometry; Bone Marrow; Bone Marrow Diseases; Cells, Cultured; Diagnostic Imaging; Diagnostic Tests, Routine; Erythrocyte Volume; Erythroid Precursor Cells; Erythropoietin; Female; Hematocrit; Hemoglobinopathies; Humans; Hypoxia; Kidney Diseases; Liver Diseases; Male; Neoplasms; Polycythemia; Receptors, Erythropoietin; Thrombocytosis

Topics: Adult; Anemia; Blood Loss, Surgical; Blood Transfusion, Autologous; Cost-Benefit Analysis; Erythropoiesis; Erythropoietin; Feedback; Hematologic Diseases; Humans; Infant, Newborn; Iron Deficiencies; Kidney; Neoplasms; Recombinant Proteins; Uremia

Topics: Anemia; Chronic Disease; Erythrocyte Count; Erythropoiesis; Erythropoietin; Humans; Infections; Kidney Failure, Chronic; Neoplasms; Rheumatic Diseases

Topics: Anemia; Animals; Antineoplastic Agents; Bone Marrow Transplantation; Erythropoietin; Fever; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; Humans; Neoplasms; Neutropenia; Recombinant Proteins; Stomatitis

Biological and gene therapy of cancer have become important components of clinical cancer research. Advances in this area are based on evidence for the presence of tumor antigens, antitumor immune responses, evasion of host control by tumors, and the recognition of host defense failure in cancer patients. These mechanisms are being corrected or exploited in the development of biological and gene therapy. Over the last decade, 9 biological therapies have received Food and Drug Administration approval, and another 12 appear promising and will likely be approved in the next few years. Our approach to gene therapy has been to allogenize tumors by the direct intratumoral injection of HLA-B7/beta2-microglobulin genes as plasmid DNA in a cationic lipid into patients with malignant melanoma. In four Phase I studies, we found a 36% response by the local injected tumor and a 19% systemic antitumor response. In other cancers, gene transfer, expression, and an intratumoral T-cell response were seen, but no clinical response was seen. A variety of follow-up studies with HLA-B7 and other genes are planned. Evasion of host control is now a major target of gene therapy. Strategies to overcome this include up-regulation of MHC and introduction of cell adhesion molecules into tumor cells, suppression of transforming growth factor and interleukin 10 production by tumor cells, and blockade of the fas ligand-fas interaction between tumor cells and attacking lymphocytes. With these approaches, it seems likely that gene therapy may become the fifth major modality of cancer treatment in the next decade.

Topics: BCG Vaccine; Clinical Trials, Phase I as Topic; Erythropoietin; Genetic Therapy; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunotherapy; Interferons; Interleukin-2; Neoplasms; United States; United States Food and Drug Administration

The pathogenesis of the anemia of cancer involves the combination of a shortened erythrocyte survival in circulation with the failure of bone marrow to increase red cell production in compensation. Inappropriate red cell production is itself related to a conjunction of factors, including impaired availability of reticuloendothelial storage iron, inadequate erythropoietin (Epo) response to anemia, and overproduction of cytokines which are capable of inhibiting erythropoiesis. Many of these cytokines may interfere with erythropoietin production by the kidney. Consequently inadequate serum erythropoietin levels are often encountered in cancer patients, though more frequently in those with solid tumors or multiple myeloma than in those with other hematologic malignancies. There is little evidence supporting a negative impact of chemotherapy, including cisplatin, on erythropoietin production. Rather, chemotherapy usually causes a transient elevation of serum Epo. Red cell transfusions are often administered to cancer patients, possibly resulting, among other deleterious effects, in enhancement of tumor growth. Recombinant human erythropoietin (rHuEpo) has thus been proposed as an alternative. RHuEpo has been shown to be safe and effective in correcting the anemia of cancer and reducing the need for transfusions. The response rate is as good in hematologic malignancies as in solid tumors, but it is extremely poor in those with myelodysplastic syndromes. The effect of rHuEpo does not differ among patients receiving or not receiving chemotherapy, including cisplatin. The probability of response is also similar in patients with adequate or inappropriate erythropoietin production before therapy, although the doses used are usually 2 to 3 times higher than in renal failure patients.

Topics: Anemia; Cytokines; Erythrocyte Aging; Erythropoiesis; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Topics: Acquired Immunodeficiency Syndrome; Autoimmune Diseases; Erythropoietin; Humans; Hypertension; Neoplasms

In many patients with malignant haematological and oncological diseases during the disease the haemoglobin concentration declines. Anaemia can be due to blood losses, less frequently to nutritional deficiency. One of frequent causes is the humoral effect of malignant disease on haematopoiesis and the development of anemia of chronic disease. Anemia of chronic disease has a complex etiology. Decreased production of erythropoietin is one of the participating factors and the pharmacological doses of erythropoietin can restore the number of erythrocytes to normal value. The authors present basic information on chronic anaemia of malignant diseases and principles of erythropoietin treatment of these patients.

Topics: Anemia; Chronic Disease; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Topics: Anemia; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Patient Selection; Predictive Value of Tests; Recombinant Proteins; Treatment Outcome

Patients undergoing cancer surgery frequently require blood, and the transfusion of allogeneic blood in these patients has been controversially linked to an increased risk of tumor recurrence. This patient population may therefore benefit from preoperative autologous blood donation (ABD) with or without epoetin alfa therapy, although the precise impact of autologous blood transfusion has not been fully explored. In some trials, preoperative ABD reduced allogeneic blood exposure by 50% in patients undergoing surgery for cancer resection, while, in another study, perioperative treatment with epoetin alfa significantly increased hematocrit (Hct) levels preoperatively and led to a reduction in postoperative allogeneic blood exposure. A combination of epoetin alfa and preoperative ABD seems a reasonable approach to reducing allogeneic blood exposure in patients undergoing cancer surgery.

Topics: Anemia; Blood Transfusion; Blood Transfusion, Autologous; Colorectal Neoplasms; Disease-Free Survival; Epoetin Alfa; Erythropoiesis; Erythropoietin; Gastrointestinal Neoplasms; Humans; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasms; Premedication; Prospective Studies; Recombinant Proteins; Survival Rate; Transfusion Reaction; Treatment Outcome

In this review, reports of the increased expression of selected genes in response to hypoxia have been summarised. The best studied mammalian hypoxia response systems are those of the erythropoietin (Epo) and the vascular endothelial growth factor (VEGF) genes, which will be described in some detail. Other genes discussed here include those encoding growth factors, cytokines, transcription factors, metabolic enzymes and DNA repair enzymes. Short DNA sequences (hypoxia response elements) governing the increased gene expression in response to hypoxia have been discovered in the vicinity of most of these genes. The review will end by analysing the possibility of exploiting tumour hypoxia via the use of hypoxia response elements for gene therapy of cancer.

Topics: Animals; Cell Hypoxia; Cytokines; DNA Repair; DNA-Binding Proteins; Endothelial Growth Factors; Erythropoietin; Genetic Therapy; Humans; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Lymphokines; Neoplasms; Nuclear Proteins; Transcription Factors; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Erythropoietin can be successfully used in the treatment of anaemia induced by chemotherapy and radiotherapy as well as for the treatment of anaemia induced by malignant disease without previous chemotherapy of radiotherapy. Erythropoietin administered during chemotherapy is effective in 50-70% patients, it has a more marked effect as a supplement to chemotherapy with cisplatinum and carboplatinum than non-platinum regimens. Erythropoietin reduces the consumption of red cell concentrates during chemotherapy on average by one half. Long-term administration of erythropoietin in anaemia caused by malignant disease alone proves most effective in multiple myeloma and in chronic lymphatic leukaemia or in non-Hodgkin lymphomas with a low malignity. The therapeutic responses defined as independence on transfusions and a rise of the haemoglobin level by at least 20 g/l, as compared with the pretreatment value, can be achieved in 60 to 80% of the patients. Erythropoietin is much less effective (10-20% therapeutic responses) in myelodysplastic syndrome, in myeloproliferative diseases or in aplastic anaemia. The authors give an account on the effectiveness of erythropoietin in different indications.

Topics: Anemia; Erythropoietin; Humans; Neoplasms

With the identification of recombinant production of the hematopoietic growth factors, these cytokines have been evaluated in the treatment of primary bone marrow failure states and after myelosuppressive chemo- or radiotherapy. Granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and erythropoietin have been approved for clinical use, and others including c-mpl-ligand (also called megakaryocyte growth and development factor or thrombopoietin) are in phase I and II trials. Most studies have been done with granulocyte and granulocyte-macrophage colony-stimulating factors; their beneficial effects are proven regarding acceleration of granulocyte recovery after chemo- and radiotherapy. In the majority of trials, this acceleration results in a reduction of infectious risks, a shortening of drug- and radiation-induced myelosuppression, and a higher chemotherapy dose intensity; however, an improved remission rate and improved long-term survival rates have not yet been definitively documented. Guidelines have been published to provide a rational basis for the use of these factors in clinical practice. It should be emphasized, however, that for many of the recommendations data from randomized clinical trials are lacking.

Topics: Acute Disease; Antineoplastic Agents; Clinical Trials as Topic; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid; Neoplasms; Recombinant Proteins; Thrombopoietin

Topics: Anemia; Bone Marrow Transplantation; Colony-Stimulating Factors; Erythropoietin; Fever; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Neoplasms; Neutropenia; Radiotherapy; Thrombocytopenia

The use of cytokines following bone marrow transplantation has become an area of increasing controversy with specific regard to indication, efficacy and cost. This review will attempt to summarize cytokine data in both adult and pediatric transplantation. Indications for cytokines following transplantation will be presented, as well as suggestions for specific issues that should be addressed in future clinical trials.

Topics: Adult; Bone Marrow Transplantation; Child; Clinical Trials, Phase III as Topic; Drug Administration Schedule; Erythropoietin; Graft Survival; Granulocyte-Macrophage Colony-Stimulating Factor; Hematologic Neoplasms; Hematopoiesis; Hematopoietic Cell Growth Factors; Humans; Interleukin-3; Neoplasms; Recombinant Fusion Proteins

With the identification and recombinant production of the hematopoietic growth factors, these cytokines have been evaluated in the treatment of primary bone marrow failure states and after myelosuppressive chemotherapy or radiotherapy. A lot of clinical trials with hematopoietic factors have been performed in patients with haematologic and oncologic diseases within the last decade. Granulocyte colony-stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF], interleukin-3, interleukin-2, erythropoietin and in phase I/II trials thrombopoietin [TPO] are available for the clinical use. At the present, there is a broad use of growth factors. Most studies have been done with G-CSF and GM-CSF, their beneficial effects are proven regarding improvement of hematopoietic recovery after chemotherapy. This results in a marked reduction of infectious risks and a shortening of drug- and radiation-induced myelosuppression. CSFs are most important in mobilizing peripheral blood progenitor cells [PBPC] and have allowed high dose therapy to be given to patients who would not have been able to undergo conventional bone marrow transplantation. However, an improved outcome and improved survival rates with standard chemotherapy protocols couldn't be documented by studies up to now, even though higher chemotherapy doses are possible by the use of hematopoietic factors.

Topics: Colony-Stimulating Factors; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoiesis; Hematopoietic Cell Growth Factors; Humans; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Neoplasms; Thrombopoietin

The anemia of malignancy is common and is related to several etiologic factors, a major one being relative erythropoietin (Epo) deficiency. Blood transfusions, the traditional therapy, provides a quick solution but is associated with complications. This was the rationale for recombinant human Epo (rHuEpo) in the treatment of anemia of cancer. Over the past few years, about 20 publications have reported the results of rHuEpo in the treatment of cancer-associated anemia in more than 850 patients with a variety of malignancies. In general, more than half of the patients responded with a significant increase in their hemoglobin level, a decrease in blood transfusion requirements, and an improved performance status and quality of life. About 4 weeks are required till the onset of effect. The hormone is well tolerated with minimal adverse effects and subcutaneous injections appear to be the preferred method of administration. Additional studies will hopefully answer several questions including optimal dosage and duration of treatment, Epo resistance, and the possibility of predicting the response.

Topics: Anemia, Aplastic; Blood Transfusion; Drug Resistance; Erythropoietin; Hemoglobins; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Time Factors; Treatment Outcome

About 30% of patients with tumors (in relation to its extent) suffer from anemia which is usually asymptomatic. Etiologically this anemia may be characterized as secondary, so called anemia of chronic diseases. Disorders of iron metabolism, blood marrow insufficiency, extracorpuscular haemolysis, catabolism of patients with tumor burden and relative deficiency of erythropoietin all play a role in its pathogenesis. Anemia of cancer patients may be usually classified as normocytic and normochromic. Indication and timing for treatment of anemia of cancer is equivocal. Successful treatment of anemia seems to improve the quality of life of cancer patients. Indication depends, of course, on the severity of anemia, degree of adaptation and the presence of clinical symptoms related to anemia. Therapy with iron or anabolics is not very effective, therapy with recombinant erythropoietin is not available for all patients, especially for its high price. Transfusion therapy should be considered more carefully in relation with some data showing the possible negative influence of allogeneic blood derivatives on the progression of tumors, especially in patients immunodeficient after high dose chemotherapy and actinotherapy.

Topics: Anemia; Blood Transfusion; Erythropoietin; Humans; Neoplasms

Chronic anemia associated with cancer often causes poor quality of life and is often exacerbated by intensive treatment. In recent controlled trials, recombinant human erythropoietin (rhEpo) proved to be well tolerated and effective in amelioration and reduction of transfusion requirements of cancer-associated anemia. Double-blind placebo-controlled trials of rhEpo in patients undergoing allogenic, but not autologous, bone marrow transplantation showed significant acceleration of the reconstitution of erythropoiesis. Multivariate analysis revealed that serum erythropoietin levels of 100 mU/mL or greater and an increase in hemoglobin by at least 0.5 g/dL was a probable response; conversely, a serum ferritin level of 400 ng/mL or greater after 2 weeks indicated a poor response to rhEpo therapy. Further studies are needed to define patient populations in whom cost-effective rhEpo therapy is justified.

Topics: Anemia; Antineoplastic Agents; Bone Marrow Transplantation; Combined Modality Therapy; Erythropoiesis; Erythropoietin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-3; Male; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Fusion Proteins; Recombinant Proteins; Transfusion Reaction

Topics: Anemia; Erythropoiesis; Erythropoietin; Female; Humans; Male; Neoplasms; Recombinant Proteins

The anaemia of chronic disease is the second most common anaemia in the world and is an underproduction anaemia with relatively low erythropoietin (EPO) values for the degree of the anaemia. This anaemia occurs with inflammation, infection, or malignancy and a principle question has been whether it would respond to recombinant human EPO (r-HuEPO). Several studies are now available to answer this question. In one study 12 of 16 patients with rheumatoid arthritis receiving r-HuEPO increased their haematocrits 6 percentage points or more and 11 of 12 reached normal haematocrits. Investigations of the effect of r-HuEPO on the anaemia of AIDS showed that patients with EPO levels of 500 U/L or less had an increase in the mean haematocrit of 4.6 percentage points with a decrease in red cell transfusions from 5.3 to 3.2 units per patient. Quality of life indices significantly improved in responders. When 413 patients with anaemia due to a wide variety of malignancies were randomized to r-HuEPO treatment, 58% of those receiving chemotherapy increased their haematocrits by at least 6 points over 12 weeks. Quality of life parameters of responders also significantly improved. Anaemia in three patients with inflammatory bowel disease also responded in 8-14 weeks to r-HuEPO and two of the three reached normal haemoglobin levels. It is clear that r-HuEPO can correct the anaemia of chronic disease and can improve the quality of life of responders.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Arthritis, Rheumatoid; Erythropoietin; Humans; Inflammatory Bowel Diseases; Neoplasms; Recombinant Proteins

Erythropoietin, the glycoprotein which regulates erythropoiesis is unique amongst the hematopoietic growth factors since it is the only one which behaves like a hormone. Produced primarily in the kidneys in adults, erythropoietin interacts with erythroid precursors in the marrow to increase red cell production. Because erythropoietin behaves like a hormone, measurements of erythropoietin in the serum have proved useful in determining when production of this hormone is inadequate. Tissue hypoxia is the only physiologic stimulus for erythropoietin production and thus, with anemia, serum erythropoietin levels should be increased. Assuming normal marrow function and adequate nutrient supplies, when anemia is associated with a low serum erythropoietin level, it can be concluded that the anemia is in part due to erythropoietin lack and should be correctable by administration of erythropoietin. As a corollary, a high serum erythropoietin level (greater than 500 mU/ml) in the presence of anemia suggests that there is end organ failure, and erythropoietin therapy is not likely to be useful.

Topics: Anemia; Bone Marrow Diseases; Erythropoietin; Humans; Neoplasms; Renal Insufficiency

Hematopoietic growth factors have already had an enormous impact on transfusion practice by eliminating or reducing the need for red blood cell transfusions in a variety of anemic states characterized by an absolute or relative decrease in erythropoietin. In addition, GM-CSF and G-CSF have stimulated the production of autologous neutrophils in febrile neutropenic patients in whom granulocyte transfusions had been considered ineffective. With the discovery of c-Mpl ligand and the promising results obtained with IL-11 and IL-3, a combination of growth factors that successfully stimulate platelet production may soon be identified. This first era in the clinical application of hematopoietic growth factors has been characterized largely by treatment of the patient to stimulate production of autologous cells or to enhance the ability of transplanted hematopoietic progenitor cells to repopulate the patient. The use of G-CSF to increase the yield of granulocytes harvested by apheresis procedures and to mobilize peripheral blood stem cells in allogeneic donors has initiated a new era in which the cell donor is treated to enhance cell production and enhance the repopulating ability of hematopoietic progenitor cells. As our understanding of hematopoiesis grows, scientists will be able to identify growth factors to overcome or correct deficient hematopoiesis. Increasingly, component transfusions will be reserved for life-threatening situations in which endogenous cell production cannot be stimulated or cell production will be too slow to prevent life-threatening events.

Topics: Animals; Antineoplastic Agents; Blood Transfusion; Blood Transfusion, Autologous; Bone Marrow Diseases; Bone Marrow Transplantation; Clinical Trials as Topic; Erythropoietin; Hematologic Diseases; Hematopoiesis; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cell Transplantation; Humans; Infant, Newborn; Infant, Premature; Interleukins; Mice; Neoplasms; Recombinant Proteins; Retrospective Studies

Recombinant human erythropoietin has been available for clinical use since 1985. It was an immediate success in treating the anemia of chronic renal failure and has also enjoyed some objective success in the treatment of other anemias in either a therapeutic or prophylactic setting, but the issues of appropriate patient selection and cost-benefit ratios are still unresolved. This review discusses the most recent literature concerning the use of recombinant human erythropoietin for the anemia associated with cancer, HIV infection, myelodysplasia, prematurity, autologous blood transfusion, bone marrow transplantation, and chronic renal failure.

Topics: Anemia; Blood Transfusion, Autologous; Erythropoietin; HIV Infections; Humans; Infant, Newborn; Infant, Premature, Diseases; Kidney Failure, Chronic; Myelodysplastic Syndromes; Neoplasms; Recombinant Proteins

The anemia associated with chronic infectious, inflammatory, and malignant diseases is characterized by a blunted erythropoietin response; for any given decrease in hemoglobin or hematocrit, the increase in serum or plasma erythropoietin is less than would be found in an equally anemic patient with iron deficiency. This observation provides a rationale for the use of recombinant human erythropoietin in the treatment of the anemia in these diseases. During the past year, new information has been reported on the pathophysiology of erythropoiesis in chronic infectious, inflammatory, and neoplastic diseases, and on the use of recombinant human erythropoietin for this anemia. This article reviews these developments.

Topics: Anemia; Chronic Disease; Clinical Trials as Topic; Erythropoietin; Humans; Infections; Inflammation; Neoplasms; Recombinant Proteins

The use of the recombinant hematopoietic growth factors G-CSF and GM-CSF have shortened the period of neutropenia, or avoided this problem, in many cancer patients who have received cytotoxic therapy. Although these benefits have been particularly striking in the autologous bone marrow and/or autologous peripheral blood progenitor cell transplant setting, most data suggest that the use of G-CSF and GM-CSF only marginally enhance recovery of the neutrophil count when administered after allogeneic bone marrow infusion. Furthermore, in the allograft setting these expensive agents have not provided benefit in the form of enhanced platelet count recovery, lessening the incidence of graft-versus-host disease, or improvement in overall survival. These data do not justify routine widespread use of G-CSF and GM-CSF and suggest that these agents should be reserved for patients who experience delay in engraftment after allogeneic bone marrow infusion. Administration of erythropoietin, on the other hand, may reduce the need for homologous red blood cell transfusions, and may increase the safety margin for both the allogeneic bone marrow recipient and as well as the donor. Recombinant hematopoietic growth factors targetted specifically to enhance platelet recovery after transplantation (such as interleukin-3, interleukin-6, and interleukin-11) have shown promise after autotransplantation and after conventional dose chemotherapy, and likely will be evaluated in the allogeneic transplant patient.

Topics: Bone Marrow Transplantation; Clinical Trials as Topic; Erythropoietin; Graft Survival; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Humans; Lymphocyte Depletion; Macrophage Colony-Stimulating Factor; Neoplasms; Neutropenia; Recombinant Proteins; Transplantation, Homologous; Treatment Outcome

Topics: AIDS-Related Opportunistic Infections; Anemia; Anemia, Hemolytic, Autoimmune; Antiviral Agents; Bone Marrow Diseases; Erythropoietin; Hematopoietic Cell Growth Factors; HIV Infections; Humans; Neoplasms; Recombinant Proteins

Topics: Animals; Bone Marrow Diseases; Bone Marrow Transplantation; Cytokines; Erythropoietin; Graft Survival; Hematologic Diseases; Hematopoiesis; Hematopoietic Cell Growth Factors; Humans; Immunologic Factors; Neoplasms; Recombinant Proteins

Erythropoietin, alone or in combination with colony-stimulating factors, is a promising agent in the treatment of patients with cancer-related 'anemia of chronic disorders', chemo/radiotherapy-induced anemia, or anemia due to myelodysplastic or myeloproliferative syndromes. In the first two groups, at least half of the patients can be expected to respond to erythropoietin alone, with an average response delay of about 4 weeks and maximal responses at weekly doses of approximately 1000 U/kg. In myelodysplastic syndromes, only 10-20% of patients respond to conventional doses of erythropoietin, but doses exceeding 1000 U/kg weekly in combination with granulocyte colony-stimulating factor yield response rates of about 40%. Although these results show that hematopoietic growth factors can be used successfully to treat cancer-related anemias, economic constraints preclude their use at the present time.

Topics: Anemia; Erythropoietin; Hematopoietic Cell Growth Factors; Humans; Neoplasms

Topics: Anemia; Blood Transfusion; Cloning, Molecular; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Erythropoietin (EPO) is a glycoprotein produced primarily by the kidney in response to tissue hypoxia, and is the principal factor regulating red blood cell production. It stimulates erythroid precursors in the bone marrow to proliferate and mature into morphologically identifiable red blood cells. This hormone acts by binding to specific high-affinity receptor on erythroid precursors. Failure to produce adequate quantities of EPO leads to severe anemia, a situation most often encountered in patients with end stage renal disease. With the application of recombinant DNA technology, the gene for this hormone has been molecularly cloned, sequenced and expressed in a biologically active form in mammalian cells. The recombinant EPO has been demonstrated to correct anemia in patients with severe end stage renal disease and alleviate their transfusion requirements. It has also been studied for anemia associated with HIV infection/zidovudine therapy, in cancer, rheumatoid arthritis, and prematurity. In addition it has been studied as a facilitator of autologous blood predeposit in patients scheduled for elective surgery and as a perisurgical adjuvant to hasten hematologic recovery and possibly avoid the need for homologous transfusion after elective surgery. When administered with the current guidelines EPO appears to be safe drug with favorable risk/benefit ratio.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Erythropoietin; Humans; Kidney Failure, Chronic; Myelodysplastic Syndromes; Neoplasms; Recombinant Proteins

The anemia of chronic disease may be viewed simply as the anemia that accompanies chronic inflammatory, infectious, or neoplastic disorders. Because these conditions are very common, the anemia of chronic disease is one of the most frequent anemias encountered, and is only second in incidence to iron-deficiency anemia. The anemia of chronic disease is primarily an anemia due to underproduction of red cells, with low reticulocyte production, and is most often a normochromic, normocytic anemia. However, in 30% to 50% of patients, the red cells are hypochromic and microcytic and, most often, the serum iron, total iron-binding capacity, and transferrin saturation are reduced in the presence of adequate iron stores. Although the differential diagnosis includes other underproduction anemias, such as those caused by vitamin and mineral deficiencies, renal failure, endocrinopathies, and myelodysplasia, it generally is easily distinguished from these conditions. Nevertheless, an understanding of the pathogenesis of this condition, as well as a means of alleviating the anemia when the chronic disorder persists, has remained elusive. Recently, major advances have occurred toward understanding the pathogenesis of the anemia of chronic disease and its treatment, and these advances are reviewed.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Anemia, Hypochromic; Animals; Arthritis, Rheumatoid; Bone Marrow; Chronic Disease; Cytokines; Erythropoietin; Humans; Incidence; Neoplasms; Recombinant Proteins

The US health care system is under increasing pressure to lower costs while maintaining quality of care. Providers will be forced to (1) measure the benefits of a particular therapy, and (2) demonstrate that the benefits justify the costs. The major components of therapeutic benefit are survival and quality of life. Chronic anemia may have little impact on survival, but studies have measured significant decrements in quality of life without therapy and increments in quality of life with therapy. This disease also presents important societal financial concerns due to its many competing therapies. The annual cost of treatment can vary from an average of a few dollars for iron supplementation to an average of $6,000 for a course of recombinant human erythropoietin. Physicians need to integrate information on therapeutic outcomes and cost to maximize individual benefit and justify the costs. The choice of therapy for anemia associated with cancer is complex because the onset of the anemia is multifactorial, and the effects of anemia may be masked by the underlying malignancy. There are insufficient data supporting a specific recommendation for transfusion or recombinant human erythropoietin therapy. The current cost-conscious environment in the United States presents an opportunity for health care providers to formally document the benefits of anemia therapy and justify the societal costs based on those benefits. Anemia is an excellent example of a condition that allows the formal analysis of disease impact and the effectiveness and cost of therapy because (1) it has multiple therapies, (2) the cost of therapy varies widely, and (3) the therapies have variable benefit depending on the individual patient. Using a model based on chronic renal failure, an outcomes structure was developed by which the impact of anemia and the therapies used to manage it can be measured. Its potential application to anemia in patients with cancer is discussed.

Topics: Anemia; Blood Transfusion; Cost-Benefit Analysis; Erythropoietin; Humans; Mortality; Neoplasms; Quality of Life; Recombinant Proteins; United States

Under normal circumstances, the circulating red blood cell mass is maintained at a level that is constant in each individual, although that level may vary by more than 10% among individuals of the same age and gender. At normal ambient oxygen tension, two factors determine the circulating red blood cell mass: red blood cell life span, which is finite and in humans approximates 120 days; and the rate of effective red blood cell production. To maintain a constant red blood cell mass, therefore, approximately 20 mL of red blood cells must be produced each day to replace those red blood cells lost from the circulation through senescence. Anemia, which may be defined functionally as lack of sufficient red blood cells to maintain adequate tissue oxygenation, develops when the demand for new red blood cells exceeds the capacity of the bone marrow to produce them. This may be due to excessive red blood cell destruction, impaired red blood cell production, bleeding, or any combination of these. Acquired anemia is always a consequence of another disorder, which must be identified to ensure that the corrective therapy is appropriate. In patients with solid tumors, multiple mechanisms for causing anemia have been identified: blood loss that is either intrinsic or iatrogenic; nutritional deficiencies involving primarily iron or folic acid; hemolysis (autoimmune, traumatic, or drug-induced); bone marrow failure due to tumor encroachment, myelofibrosis, or marrow necrosis; infection; inflammation; or simply the presence of a cancer elsewhere in the body. The three noted causes of marrow failure share a common denominator: impaired production of erythropoietin. For any degree of anemia, a patient with cancer produces much less erythropoietin than expected and, therefore, cannot compensate for impaired red blood cell production. Inflammation or infection can exacerbate this situation. Indeed, anemia in patients with cancer appears to behave much like that in patients with chronic renal failure who become anemic because of the inability of the kidneys to produce erythropoietin adequately. The cause of impaired erythropoietin production in patients with cancer who have anemia is not entirely understood, but may be due in part to the production of inflammatory cytokines in response to the tumor. Such cytokines also would be expected to blunt the ability of the bone marrow to respond to the available circulating erythropoietin.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Anemia; Erythropoietin; Humans; Neoplasms

Recombinant human erythropoietin (rHuEPO) is approved for the treatment of the anemia of chronic kidney failure and anemia associated with zidovudine therapy of acquired immunodeficiency syndrome. In chronic kidney failure and other conditions such as cancer and hematologic malignancies, the endogenous erythropoietin response to anemia is blunted and rHuEPO might be beneficial in these conditions.. We reviewed preclinical and clinical trial results with rHuEPO in a variety of conditions.. It is clear that chronic anemias of several causes respond to pharmacologic doses of rHuEPO. rHuEPO has been shown to enhance erythropoiesis before elective surgery, reduce the number of patients exposed to homologous blood at the time of coronary artery bypass grafting, reverse the anemia in most patients with cancer, and result in clinical benefit in 25% to 35% of patients with myelodysplasia.. rHuEPO is important as a therapeutic means to correct anemia. rHuEPO is likely to be useful in correcting chronic anemias or anemias associated with chemotherapy, particularly in those patients with expected long-term survival. Issues to be resolved include the accurate prediction and targeting of rHuEPO therapy for patients most likely to respond.

Topics: Anemia; Blood Transfusion, Autologous; Clinical Trials as Topic; Erythropoietin; Humans; Neoplasms; Recombinant Proteins; Surgical Procedures, Operative

Haematopoietic growth factors help patients with intense chemotherapy and patients after transplantation of bone marrow to overcome the critical stage of leucopenia. In the submitted paper the authors present more detailed data on the results of investigations evaluating G-CSF, GM-CSF and erythropoietin in patients with anti-tumourous treatment. Both leucocytic growth factors, G-CSF and GM-CSF shorten the period of leucopenia by approximately one week which means a substantial reduction of the number of infectious complications and also a reduction of the hospitalization period. The price of the mentioned growth factors which is still high as compared with the costs of intensive treatment of septicaemia in leukopenic patients. To the authors' surprise, comparing an equal period of time, treatment of septicaemia is associated with much higher costs than administration of G-CSF which can prevent sepsis or reduce its duration.

Topics: Czechoslovakia; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunocompromised Host; Neoplasms; Neutropenia

Clinical usefulness of cytokines in cancer treatment has been described. Cytokines presently used in clinical practice are IFNs, IL-2, and hematopoietic growth factors. IFNs and IL-2 used with an expectation of direct antitumor effect of these cytokines have been proven to be specifically effective against certain types of tumors. Hematopoietic growth factors have been used as the adjuvant drugs in cancer treatment and proven to be effective against neutropenia and associated infections after chemotherapy and bone marrow transplantation. Future development of new cytokines and trials on the combination among cytokines and cytokines with chemotherapeutic agents, will promote the usefulness of cytokines in cancer treatment.

Topics: Antineoplastic Agents; Bone Marrow Transplantation; Colony-Stimulating Factors; Erythropoietin; Humans; Infections; Interferons; Interleukin-2; Neoplasms; Neutropenia; Recombinant Proteins

The results of the multicenter trials demonstrate that r-HuEPO therapy can increase the hematocrits of anemic patients with advanced cancer. The multicenter trials were undertaken because, in previous smaller trials without placebo controls, patients with cancer and anemia had been shown to be likely responders to r-HuEPO therapy. To varying degrees in these trials, RBC transfusion requirements were eliminated or decreased in comparison to those of placebo-treated patients, and anemia was lessened or corrected in the r-HuEPO groups. The side effects of r-HuEPO treatment were minor; anemic patients with advanced cancer receiving r-HuEPO therapy did not develop significant hypertension, seizures, or thrombotic events, and progression of tumor was not observed. Moreover, patients in the multicenter trials whose hematocrits increased to 38% or greater, or increased 6 percentage points or more, experienced significant improvement in all aspects of the quality of their lives. On the basis of these trials, r-HuEPO therapy appears to treat effectively the anemia of cancer. The importance of eliminating the need for transfusions and preventing sensitization to human leukocyte antigens will be major factors affecting the clinical future of r-HuEPO.

Topics: Anemia; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

We review data concerning site and regulation of erythropoietin (EPO) production, its effects on target tissue, routes of administration and clinical applications. In the anaemia of chronic renal failure (ACRF) treatment with recombinant human erythropoietin (r-Hu-EPO) has been shown to be effective in both improvement of the anaemia and increase in quality of life. In the anaemia of chronic disease (ACD), associated with various malignant, infectious and inflammatory disorders, many investigators have demonstrated an inappropriately low EPO response to anaemia. Therapeutic trials in patients with ACD mostly lacked sufficient numbers of patients for evaluation of the effects. The results obtained from some studies in AIDS and rheumatoid arthritis and the effect on the number of units of autologous blood obtained from patients planned for elective surgery are encouraging, however. Adverse reactions of r-Hu-EPO treatment are mainly confined to the ACRF population and include hypertension, shunt thrombosis and pain at the injection site. The exact mechanism of action of EPO is not yet fully understood. Large scale clinical trials are required to establish its effects on both the anaemia and quality of life in anaemias other than ACRF.

Topics: Anemia; Chronic Disease; Clinical Protocols; Clinical Trials as Topic; Drug Administration Schedule; Erythropoietin; Humans; Infections; Inflammation; Kidney Failure, Chronic; Neoplasms

Topics: Acquired Immunodeficiency Syndrome; Bone Marrow Transplantation; Colony-Stimulating Factors; Erythropoietin; Hematopoietic Cell Growth Factors; Humans; Neoplasms; Neutropenia; Tumor Necrosis Factor-alpha; Zidovudine

Topics: Anemia; Bone Marrow Transplantation; Clinical Trials as Topic; Double-Blind Method; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; Humans; Immunologic Factors; Interleukin-3; Macrophage Colony-Stimulating Factor; Myelodysplastic Syndromes; Neoplasms; Paraneoplastic Syndromes; Randomized Controlled Trials as Topic; Recombinant Proteins

Topics: Animals; Clinical Trials as Topic; Colony-Stimulating Factors; Erythropoietin; Fibroblast Growth Factors; Growth Hormone; Growth Substances; Humans; Insulin-Like Growth Factor I; Interleukins; Neoplasms; Platelet-Derived Growth Factor; Recombinant Proteins; Transforming Growth Factor alpha; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Wound Healing

Recombinant human erythropoietin (r-HuEPO) has been shown to be remarkably effective in raising the hemoglobin concentrations and improving the quality of life of patients with chronic renal disease. It is currently under investigation for treatment of patients with nonrenal anemias associated with cancer chemotherapy, acquired immunodeficiency syndrome, rheumatoid arthritis, and other chronic illnesses. To date, investigators have shown that patients with mild anemia and low endogenous erythropoietin (EPO) production may be good candidates for such treatment. Conversely, studies have shown that patients with severe anemia and serum EPO concentrations of above 500 mU/mL apparently do not respond to doses used for patients with mild anemia or chronic renal disease. Large doses of r-HuEPO may be of use in such patients, and clinical trials are in progress to determine if it is at least possible to make these patients transfusion-independent.

Topics: Anemia; Chronic Disease; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Recombinant human erythropoietin (r-HuEPO) has been shown to correct anemia and alleviate transfusion dependency in patients with end-stage renal disease, to ameliorate anemia and reduce transfusion requirements in anemic patients with acquired immunodeficiency syndrome, to correct anemia in patients with rheumatoid arthritis, and to facilitate predeposit autologous blood donation. Cancer is frequently complicated by anemia, and a survey of serum erythropoietin concentrations in anemic cancer patients showed inappropriately low concentrations for the degree of anemia. Initial clinical trials suggest that r-HuEPO can correct the anemia associated with malignancy, but the exact role of the recombinant hormone in this situation remains to be defined.

Topics: Anemia; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

There exists a potential for change in the approach to the management of the patient with chronic disease, specifically, the anemia of chronic disease (ACD). One of the components in the pathophysiology of ACD is inadequate erythropoietin response. Normally, as anemia develops, the erythropoietin level does not begin to increase until the hematocrit level decreases below 35%. However, the increase in the erythropoietin level is blunted in ACD. Increasing the hematocrit level by transfusion or recombinant human erythropoietin (r-HuEPO) treatment can subjectively and objectively improve the ACD patient's symptoms and performance. Although objective data in support of blood transfusions do exist, this treatment can carry risks of acute and chronic reactions, infection, and possibly immunosuppression. Treatment with r-HuEPO is a safer, nontransfusion means of increasing the hematocrit level of the patient with ACD symptoms.

Topics: Anemia; Animals; Blood Transfusion; Chronic Disease; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

The last few years have seen an enormous increase in our knowledge on the haematopoietic growth factor erythropoietin (Epo), firstly with its purification and determination of its primary amino acid sequence, and more recently with the isolation of the Epo gene and its expression in mammalian cell lines. This review article summarizes the crucial biological features of Epo and critically examines the main results obtained in clinical trials on humans.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Animals; Erythropoietin; Humans; Kidney Diseases; Neoplasms; Recombinant Proteins; Zidovudine

Topics: Erythropoietin; Hemoglobins; Humans; Myelodysplastic Syndromes; Neoplasms; Recombinant Proteins

The development of recombinant human erythropoietin (Epo), along with a sensitive and reproducible assay for plasma Epo, has resulted in new potential applications for the treatment of medical and surgical anemias. A series of studies have defined a role for Epo therapy in the perisurgical setting to include the facilitation of autologous blood procurement and to facilitate postoperative erythropoiesis in order to minimize homologous blood transfusion requirements. Other possible applications of Epo therapy include the treatment of medical illnesses. Clinical trials to date have demonstrated that Epo therapy can correct the anemias of renal insufficiency, of rheumatoid arthritis, and of acquired immunodeficiency syndrome (AIDS) patients undergoing antiviral therapy. Clinical trials investigating the application of Epo therapy in the oncologic setting are in progress. These developments herald a new age in transfusion medicine, which includes the use of pharmacologic therapies in blood conservation strategies.

Topics: Anemia; Blood Transfusion, Autologous; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Neoplasms; Recombinant Proteins; Surgical Procedures, Operative

Myelosuppression is the main limiting factor in cancer chemotherapy. The development of recombinant hematopoietic growth factors which stimulate myeloid progenitors and mainly neutrophil precursor cells leads to the evaluation of their potential activity in numerous fields of oncology. The available clinical trials have demonstrated the ability of G-CSF (granulocyte colony-stimulating factor) and GM-CSF (granulocyte-macrophage colony-stimulating factor) to accelerate neutrophil recovery following cytotoxic chemotherapy, and therefore to reduce the incidence of neutropenic febrile episodes and thereby improve the quality of life of patients receiving chemotherapy. The main goals of the future studies will be to determine to what extent the increase of dose intensity may lead to higher response rates and survival at least in patients with chemosensitive tumors.

Topics: Animals; Antineoplastic Agents; Drug Administration Schedule; Erythropoietin; Hematopoietic Cell Growth Factors; Humans; Neoplasms; Neutropenia

Topics: Anemia; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

The currently available radioimmunoassay for erythropoietin (Epo) using recombinant reagents is an accurate, reproducible, sensitive and specific assay which can be used to identify whether lack of Epo is contributing to anemia and, by extension, whether therapy with recombinant Epo might be appropriate. Elevation of the serum Epo level with anemia suggests that a marrow abnormality is the cause of the anemia, while a "high" Epo level in a non-anemic or plethoric patient suggests the presence of hypoxia or autonomous Epo production. Liver disease can elevate the serum Epo level, while modest degrees of anemia do not affect it appreciably. The lowest Epo levels occur in polycythemia vera, but in a particular patient this finding is not completely diagnostic.

Topics: Anemia, Hemolytic; Erythropoietin; Female; Humans; Infant, Newborn; Infant, Premature; Infections; Inflammation; Neoplasms; Polycythemia; Pregnancy; Radioimmunoassay

In summary, anemia developing in a patient with cancer can be due to several different factors. A relative failure of erythropoiesis, in conjunction with a modestly shortened erythrocyte survival, is the most likely explanation for the anemia and can occur in patients with or without bone marrow invasion. Several theories have been proposed to explain the mechanism of limited red cell production in cancer. Internal iron starvation and cancer toxic factors have been widely implicated. Immunoglobulin inhibitors of erythropoiesis occur in the rare entity, pure red cell aplasia, which is sometimes associated with thymomas. Autoimmune hemolytic anemia and microangiopathic hemolytic anemia can also occur in patients with solid cancers, pointing out the need for a complete evaluation of anemia in any patient with recent-onset anemia. Successful treatment and prognostic implications of anemia in cancer is dependent on proper diagnosis.

Topics: Anemia; Anemia, Aplastic; Anemia, Hemolytic; Anemia, Megaloblastic; Anemia, Myelophthisic; Bone Marrow; Erythropoiesis; Erythropoietin; Humans; Intestinal Absorption; Iron; Mononuclear Phagocyte System; Neoplasms

Topics: Anemia; Arthritis, Rheumatoid; Chronic Disease; Diagnosis, Differential; Erythropoiesis; Erythropoietin; Humans; Iron; Neoplasms

Topics: Animals; Colony-Stimulating Factors; Erythropoietin; Hematologic Diseases; Humans; Mice; Mice, Nude; Middle Aged; Neoplasm Transplantation; Neoplasms

Tansplantability, growth, morphology, and function of xenotransplanted human tumors, such as carcinomas of the lung, liver, breast, choriocarcinoma, and blastomas of the liver, lung, kidney, and uterus, are described. From the tumor take rate, it is clear that xenotransplantation cannot be used for the study of every human tumor: slow-growing tumors are difficult to analyze, and functioning adenomas and low-grade malignant carcinomas are at present almost impossible to study by this approach. From the authors' transplantation experience, tumor antigenicity to nude mice with no T-cell function, either tumor specific or species specific, was suspected. Therefore, the growth in nude mice may not equate to that in the human body. The stroma of the transplanted tumor, which is most likely of mouse origin, might also alter the growth rate, as it did the histology of some tumors. Another possible hindrance that has not been described in the text is the mouse endogenous virus. Serially transplanted human tumors are often infected with C particles, which could well influence the tumor growth and character. In spite of the presence of some factors unfavorable for the study of human tumors through xenotransplantation, it has, nevertheless, been clearly shown that the nude mouse/human tumor system is a very useful tool for functional analysis of tumors in relation to growth, differentiation, and morphology, such as eutopic or ectopic production of various hormones, AFP, normal serum proteins, colony-stimulating factor, erythropoietin, and so on. This system can be employed to elucidate the production of many other biologically active and inactive substances by a variety of tumors and their effects on the host in the future and should provide better understanding of human cancers. Attempts to induce differentiation and to change the biologic behavior of xenotransplanted human malignant tumors have failed so far, except for induced dormancy of breast carcinoma under unfavorable hormonal conditions. This line of investigation may have particular import on cancer research, particularly in relation to the biology and treatment of human cancers.

Topics: alpha-Fetoproteins; Animals; Blood Proteins; Breast Neoplasms; Carcinoma; Carcinoma, Adenoid Cystic; Cell Division; Choriocarcinoma; Erythropoietin; Female; Graft Survival; Hormones, Ectopic; Humans; Kidney Neoplasms; Liver Neoplasms; Liver Neoplasms, Experimental; Lung Neoplasms; Male; Mesenchymoma; Mice; Mice, Nude; Middle Aged; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms; Neoplasms, Experimental; Neoplasms, Hormone-Dependent; Pregnancy; Transplantation, Heterologous

Topics: Adrenocorticotropic Hormone; Calcitonin; Erythropoietin; Gonadotropins; Growth Hormone; Hormones, Ectopic; Humans; Hypercalcemia; Hypoglycemia; Neoplasms; Neurophysins; Oxytocin; Paraneoplastic Endocrine Syndromes; Parathyroid Hormone; Peptides; Placental Lactogen; Prolactin; Radioimmunoassay; Receptors, Cell Surface; Thyrotropin; Vasopressins

Increasing numbers of endocrine active tumors are being reported. The production of hormonal substances not generally associated with the tissues involved may directly or indirectly concern the gynecologist. Identification of these occurrences may be important in the diagnosis of occult neoplasms or obscure tumor effects. In addition, observation of the level of aberrant hormone secretion may be important therapeutic and prognostic measure. Detection may result from the investigation of apparent inappropriate and endocrine syndromes or routine screening in cases of known tumors. Proof of the actual production of hormone by the tumors and complete identification of the material in question generally requires extensive biologic, chemical, physical, and immunologic investigation. The most likely mechanisms for aberrant hormone production by tumors are derepression of the genome or the occurrence of chance biosynthetic anomalies coincident with neoplastic nuclear alterations. Endocrine active substances of interest to the gynecologist produced under these circumstances include gonadotropin, lactogens, thyrotropins, and adrenocortico-tropin, as well as calcium-mobilizing and erythropoietic substances.

Topics: Adrenocorticotropic Hormone; Biological Assay; Chorionic Gonadotropin; DNA; Erythropoietin; Female; Follicle Stimulating Hormone; Genetic Code; Genital Neoplasms, Female; Hormones, Ectopic; Humans; Luteinizing Hormone; Melanocyte-Stimulating Hormones; Neoplasms; Paraneoplastic Endocrine Syndromes; Parathyroid Hormone; Peptides; Placental Lactogen; Pregnancy; Prolactin; Radioimmunoassay; RNA, Messenger; Serotonin; Thyrotropin; Transcription, Genetic

Topics: Adrenocorticotropic Hormone; Calcitonin; Child; Erythropoietin; Gastrins; Glucagon; Gonadotropins; Growth Hormone; Hormones, Ectopic; Humans; Insulin; Male; Melanocyte-Stimulating Hormones; Neoplasms; Parathyroid Hormone; Prostaglandins; Secretin; Serotonin; Thyrotropin; Vasopressins

Topics: Anemia; Animals; Diagnosis, Differential; Erythropoietin; Humans; Mice; Neoplasms; Polycythemia; Polycythemia Vera

Topics: Adenocarcinoma; Adrenocorticotropic Hormone; Arginine; Biliary Tract Diseases; Bronchial Neoplasms; Carcinoma; Chorionic Gonadotropin; Colonic Neoplasms; Cushing Syndrome; Erythropoietin; Female; Follicle Stimulating Hormone; Growth Hormone; Gynecomastia; Hormones, Ectopic; Humans; Hypercalcemia; Lactation Disorders; Lung Neoplasms; Luteinizing Hormone; Models, Biological; Neoplasms; Paraganglioma; Paraneoplastic Endocrine Syndromes; Polycythemia; Pregnancy; Prolactin; Thyroid Neoplasms; Vasopressins

Topics: Erythropoietin; Hormones, Ectopic; Humans; Hypoxia; Kidney; Kidney Diseases, Cystic; Kidney Neoplasms; Neoplasms; Oxygen; Polycythemia; Prostaglandins; Regional Blood Flow

Topics: Calcitonin; Erythropoietin; Female; Growth Hormone; Hormones, Ectopic; Humans; Neoplasms; Paraneoplastic Endocrine Syndromes; Placental Lactogen; Prolactin; Renin; Serotonin; Thyrotropin; Vasopressins

Topics: Adrenocorticotropic Hormone; Chorionic Gonadotropin; Erythropoietin; Gastrins; Genetic Code; Gonadotropins, Pituitary; Hormones; Humans; Insulin; Insulin Secretion; Melanocyte-Stimulating Hormones; Neoplasms; Serotonin; Skin; Skin Neoplasms; Syndrome

Topics: Animals; Antibodies; Dogs; Erythropoietin; Fluorescent Antibody Technique; Glomerulonephritis; Graft Rejection; Haplorhini; Histocompatibility; Humans; Immunoglobulins; Immunosuppression Therapy; Immunosuppressive Agents; Kidney; Kidney Transplantation; Macaca; Neoplasms; Pan troglodytes; Papio; Renin; Transplantation Immunology; Transplantation, Autologous; Transplantation, Heterologous; Transplantation, Homologous

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Brain Neoplasms; Carcinoma; Carcinoma, Bronchogenic; Carcinoma, Hepatocellular; Carcinoma, Squamous Cell; Cerebellar Neoplasms; Child; Child, Preschool; Choriocarcinoma; Cushing Syndrome; Diagnosis, Differential; Erythropoietin; Female; Gonadotropins; Hemangiosarcoma; Hormones, Ectopic; Humans; Hypercalcemia; Hypoglycemia; Infant; Infant, Newborn; Insulin; Insulin Secretion; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Male; Neoplasms; Parathyroid Hormone; Pheochromocytoma; Polycythemia; Pregnancy; Teratoma; Testicular Neoplasms; Thymus Neoplasms

Topics: Anemia; Animals; Chemical Phenomena; Chemistry; Erythrocyte Aging; Erythropoiesis; Erythropoietin; Humans; Hypoxia; Kidney Failure, Chronic; Neoplasms; Oxygen Consumption; Polycythemia Vera

Topics: Anemia; Anemia, Hypochromic; Anemia, Sideroblastic; Animals; Arthritis, Rheumatoid; Bone Marrow; Chronic Disease; Copper; Disease Models, Animal; Endotoxins; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Freund's Adjuvant; Hematocrit; Humans; Infections; Iron; Mononuclear Phagocyte System; Neoplasms; Porphyrins; Protein Binding; Rats; Transferrin

Topics: Adrenocorticotropic Hormone; Erythropoietin; Female; Gastrins; Gonadotropins; Hormones, Ectopic; Humans; Insulin; Male; Melanocyte-Stimulating Hormones; Neoplasms; Parathyroid Hormone; Thyrotropin; Vasopressins

Topics: Adrenocorticotropic Hormone; Endocrine System Diseases; Erythropoietin; Gynecomastia; Hormones, Ectopic; Humans; Hypercalcemia; Hyperthyroidism; Hypoglycemia; Hyponatremia; Insulin; Luteinizing Hormone; Melanocyte-Stimulating Hormones; Neoplasms; Parathyroid Hormone; Polycythemia; Puberty, Precocious; Thyrotropin; Vasopressins

Topics: Adrenocorticotropic Hormone; Animals; Chemical Phenomena; Chemistry; Erythropoietin; Gastrins; Gonadotropins; Hormones, Ectopic; Humans; Immunochemistry; Melanocyte-Stimulating Hormones; Neoplasms; Parathyroid Hormone; Thyrotropin; Vasopressins

Topics: Adrenocorticotropic Hormone; Calcitonin; Chorionic Gonadotropin; Endocrine System Diseases; Erythropoietin; Gastrins; Hormones, Ectopic; Humans; Insulin; Lung Neoplasms; Neoplasms; Serotonin; Thyrotropin; Vasopressins

Anemia is a common side effect of myelosuppressive chemotherapy; however, chemotherapy-induced anemia (CIA) management options are suboptimal. We evaluated the efficacy and safety of roxadustat in this setting. This open-label Phase 2 study included patients with non-myeloid malignancies and CIA (hemoglobin [Hb] ≤10 g/dL) who had planned concurrent myelosuppressive chemotherapy for ≥8 additional weeks. Oral roxadustat was administered for ≤16 weeks (starting dose 2.0 or 2.5 mg/kg, then titrated every 4 weeks). The primary efficacy endpoint was mean maximum change in Hb within 16 weeks of baseline without red blood cell (RBC) transfusion. Patients were assigned to roxadustat 2.0 (n = 31) or 2.5 mg/kg (n = 61) starting doses, and 89 were assessed for efficacy. The mean (standard deviation) maximum Hb change from baseline without RBC transfusion was 2.4 (1.5) and 2.5 (1.5) g/dL in the roxadustat 2.0 and 2.5 mg/kg groups, respectively. Median (range) time to Hb increase of ≥2 g/dL was 71 (57-92) days. Twelve patients (14.5%) had RBC transfusions (Week 5 to the end of treatment). Roxadustat was efficacious regardless of tumor type and chemotherapy regimen. Deep vein thrombosis (DVT) and pulmonary embolism (PE) occurred in 14 (15.2%) and nine (9.8%) patients, respectively, and three had serious adverse events attributed to roxadustat in the opinion of the investigators (PE: n = 2 [2.2%]; DVT: n = 1 [1.1%]). Roxadustat increased Hb in patients with CIA regardless of tumor type and chemotherapy regimen. Adverse events were consistent with observations in patients with advanced-stage malignancies.

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Glycine; Hematinics; Hemoglobins; Humans; Isoquinolines; Neoplasms

Anemia is the most common and serious cancer-related complication. This study aimed to evaluate the efficacy of administration of ferric carboxymaltose without erythropoiesis-stimulating agents for treating anemia in cancer patients. Moreover, we identified the biomarkers of hemoglobin response to predict the need for iron therapy.. We enrolled patients with solid cancers who were treated at a single institute (Samsung Medical Center, South Korea), from April 2015 to July 2017, in this prospective single-arm Phase II clinical trial. Patients received intravenous ferric carboxymaltose (1,000 mg) infusion on the first day (visit 1) of treatment. The primary end point was the number of hemoglobin responders, defined as patients with an increase in hemoglobin level ≥ 1.0 g/dL from the baseline, a hemoglobin level ≥ 11.0 g/dL, or both, within an 8-week observation period (week 3, 6, or 8). Secondary end points included changes in transferrin saturation and levels of soluble transferrin receptors, hepcidin, erythropoietin, interleukin-6, and C-reactive protein (CRP) at each visit. Of the 103 recruited patients, 92 were eligible for analysis. The mean patient age was 57.3 ± 12.5 years, and 54.3% of the patients were women. The most common diagnoses were breast cancer (n = 23, 25.1%), lung cancer (n = 21, 22.9%), gastrointestinal cancer (n = 20, 20.9%), and lymphoma (n = 16, 17.7%). A hemoglobin response was observed in 36 (39.1%), 53 (57.6%), and 61 (66.3%) patients in the third, fifth, and eighth weeks, respectively. The mean increase in hemoglobin levels from the baseline to the end of treatment was 1.77 ± 1.30 g/dL. Baseline values of hepcidin (p = 0.008), total iron binding capacity (p = 0.014), ferritin (p = 0.048), and CRP (p = 0.044) were significantly different between the responder and nonresponder groups. Multiple logistic regression analysis for baseline anemia-related biochemical variable significantly associated with the hemoglobin response showed that only baseline hepcidin level was a significant factor for hemoglobin response (odds ratio = 0.95, 95% confidence interval 0.90-1.0, p = 0.045). Hemoglobin responders had significantly lower hepcidin levels than nonresponders (mean [±standard deviation], 13.45 [±14.71] versus 35.22 [±40.470 ng/ml]; p = 0.007). However, our analysis had some limitations such as the different patient characteristics in the studies that were included, institutional differences in the measurement of hepcidin level, and missing data on long-term safety. Therefore, our findings need further validation.. Intravenous ferric carboxymaltose (1,000 mg) monotherapy increases hemoglobin levels without serious adverse events in patients with cancer. Hepcidin is a useful biomarker for predicting iron requirement in cancer patients.. Clinicaltrials.gov NCT02599012.

Topics: Anemia; Antineoplastic Agents; Biomarkers; Erythropoietin; Female; Ferric Compounds; Hemoglobins; Hepcidins; Humans; Infusions, Intravenous; Male; Maltose; Middle Aged; Neoplasms; Pilot Projects; Republic of Korea; Transferrin; Treatment Outcome

Darbepoetin alfa (DA) is an erythropoiesis-stimulating agent (ESA) approved for treating chemotherapy-induced anemia (CIA). Safety concerns have prompted changes to the ESA-product information, which now recommends initiating ESAs at hemoglobin (Hb) levels < 10 g/dL (US) or ≤ 10 g/dL (EU). The present exploratory analysis of a DA trial examined how baseline-Hb levels at ESA initiation affect transfusion rates, Hb response, and safety outcomes in CIA patients. Data were retrospectively analyzed from a phase 3 trial of CIA patients randomised to 500 mcg DA every 3 weeks (Q3 W) or to 2.25 mcg/kg DA weekly (QW) for 15 weeks. In the current analysis, data were reanalyzed by baseline-Hb categories of <9 g/dL (n = 126), 9 to <10 g/dL (n = 225), and ≥ 10 g/dL (n = 354). The Q3 W and QW groups were combined. Transfusion rates were highest in the <9 g/dL baseline-Hb group in all time periods examined. The Kaplan-Meier percentage (95% CI) of patients achieving Hb ≥ 10 g/dL was 68% (59, 78) and 88% (82, 92) in the <9 g/dL and 9 to <10 g/dL baseline-Hb groups, respectively. With lower baseline-Hb, incidence of a ≥ 1 g/dL-Hb rise in 14 days progressively decreased. Incidence of venous thromboembolic events was similar in all baseline-Hb groups and similar between patients with or without a ≥ 1 g/dL-Hb rise in 14 days. Overall, transfusion risk increased and Hb response decreased at lower baseline-Hb levels in this exploratory analysis. When following ESA-product information to initiate ESAs at Hb ≤ 10 g/dL, the greatest benefit may be achieved when initiating close to 10 g/dL. Prospective studies are needed to further examine this hypothesis.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Blood Transfusion; Darbepoetin alfa; Double-Blind Method; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Risk; Young Adult

HX575 was approved in the European Union in August 2007 as the first-ever biosimilar epoetin-α product. The present study extended the safety database on HX575 by monitoring adverse events (AEs) in clinical practice. Hemoglobin (Hb) levels and HX575 doses were recorded for the assessment of efficacy. This open, 6-month single-arm study was conducted in 10 European countries with a target enrollment of 1,500 patients with anemia due to chronic kidney disease (CKD). HX575 was intravenously (i.v.) administered aiming at an Hb target of 10 - 12 g/dl. Most patients (92.3%) had already received erythropoiesis stimulating agents (ESAs) treatment before enrolment into this study; the recorded treatments mainly comprised i.v. or subcutaneous (s.c.) administration of epoetin-α, epoetin-β or darbepoetin. The study period covered 770 patient years. The observed AE profile was in line with expectations for this patient population. Thrombotic vascular events (TVEs) were reported in 11.9% of patients (0.2612 per patient year). Tumor incidence was 1.4% (0.0299 per patient year). No subject developed anti-epoetin antibodies. Mean Hb levels were effectively maintained between 11.2 and 11.3 g/dl following the conversion from a broad spectrum of pre-study ESA treatments with stable overall mean i.v. HX575 doses. The proportion of patients within the Hb target range increased from 57.5% at baseline to 66.8% at study end.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Biomarkers; Biosimilar Pharmaceuticals; Chronic Disease; Epoetin Alfa; Erythropoietin; Europe; Female; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Kidney Diseases; Male; Middle Aged; Neoplasms; Prospective Studies; Recombinant Proteins; Thrombosis; Time Factors; Treatment Outcome; Young Adult

Fatigue is frequent in cancer patients undergoing chemotherapy. Erythropoietins (EPO) have shown well-documented effects on these patients, and administered in pharmacological doses, may reduce the need for transfusion of blood cells and improve quality of life (QoL). An explorative, descriptive, non-randomised intervention study using semi-structured interviews was conducted with the aim to gain an insight into the effects and experiences associated with EPO treatment in combination with a structured 6-week physical exercise intervention. Sixteen cancer patients with evidence of disease, who had received at least one cycle chemotherapy, participated. Participants received 500 μg Darbepoetin Alfa (DA) every 3 weeks during the intervention. Four typologies of patients were identified with regard to DA effects. The interviews revealed that eleven patients experienced some kind of immediate improvement in cognitive and emotional functioning, and subjective daily well-being. Furthermore physical improvement and changes in QoL outcomes showed no significant differences between the study group and a reference group. A significant increase in the hemoglobin concentration (7.14-7.87 mmol/L, P<0.05) was found in the study group. The future use of EPO in cancer patients is hampered by the reported negative influence of EPO on the prognosis in some diagnoses and should be based on randomized studies.

Topics: Adolescent; Adult; Aged; Darbepoetin alfa; Drug-Related Side Effects and Adverse Reactions; Erythropoietin; Exercise Therapy; Fatigue; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Treatment Outcome; Young Adult

Functional iron deficiency may impair response to erythropoiesis-stimulating agents (ESAs) in iron-replete patients with chemotherapy-associated anemia (CAA). This study evaluated whether coadministration of parenteral iron improves ESA efficacy in patients with CAA.. This prospective, multicenter, randomized trial enrolled 502 patients with hemoglobin (Hb) less than 11 g/dL who were undergoing chemotherapy for nonmyeloid malignancies. All patients received darbepoetin alfa once every 3 weeks and were randomly assigned to receive either ferric gluconate 187.5 mg intravenously (IV) every 3 weeks, oral daily ferrous sulfate 325 mg, or oral placebo for 16 weeks.. There was no difference in the erythropoietic response rate (ie, proportion of patients achieving Hb ≥ 12 g/dL or Hb increase ≥ 2 g/dL from baseline): 69.5% (95% CI, 61.9% to 76.5%) of IV iron-treated patients achieved an erythropoietic response compared with 66.9% (95% CI, 59.1% to 74.0%) who received oral iron and 65.0% (95% CI, 57.2% to 72.3%) who received oral placebo (P = .75). There were also no differences in the proportion of patients requiring red cell transfusions, changes in quality of life, or the dose of darbepoetin administered. Adverse events (AEs) tended to be more common in the IV iron arm: grade 3 or higher AEs occurred in 54% (95% CI, 46% to 61%) of patients receiving IV iron compared with 44% (95% CI, 36% to 52%) who received oral iron and 46% (95% CI, 38% to 54%) who received oral placebo (P = .16).. In patients with CAA, addition of IV ferric gluconate to darbepoetin failed to provide additional benefit compared with oral iron or oral placebo.

Topics: Administration, Oral; Anemia; Antineoplastic Agents; Darbepoetin alfa; Dietary Supplements; Erythropoietin; Female; Ferric Compounds; Hematinics; Humans; Iron; Male; Middle Aged; Neoplasms; Prospective Studies

Chemotherapy-induced anemia is a frequent complication in cancer treatment. The aim was to develop a pharmacokinetic (PK) model that describes the time-dependent decline of epoetin alfa (rHuEPO) clearance following thrice (t.i.w.) or once (q.w.) weekly subcutaneous injections in cancer patients using a population PK approach. Serum concentrations of rHuEPO were available retrospectively from a phase I study. A one-compartment model with first-order elimination described rHuEPO PK. Sequential zero- and first-order (k(a)) processes with duration (t(lag)) characterized the absorption. Population PK analysis was performed using NONMEM. The influence of several covariates was tested. Model evaluation was performed using visual predictive check. Precision of parameter estimates was assessed by standard errors and confidence intervals determined by bootstrap analysis. Apparent clearance (CL/F) and volume of distribution (V(c)/F) were 25.6% lower and 29.2% higher for q.w. than t.i.w. groups. RHuEPO was absorbed for 10% during 24.6 h through the zero-order process. Following which 90% of the dose was absorbed through the first-order process with k(a) of 0.033 h⁻¹. The most significant covariates were the time-dependent decrease of CL/F with an increase in body weight, a decrease in reticulocyte count, a decrease in hemoglobin baseline, an increase in total number of chemotherapy cycles, and platinum-containing chemotherapy. AGE served as an important covariate on FRAC and k(a). Visual predictive check showed no deviation from observed values. The PK model adequately predicted rHuEPO concentration-profiles in all individuals. Relevant covariates were identified and incorporated into the model.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Middle Aged; Models, Biological; Neoplasms; Nonlinear Dynamics; Recombinant Proteins; Retrospective Studies; Time Factors; Tissue Distribution

Anaemia is a highly prevalent condition in cancer patients impacting on morbidity, mortality and quality of life. Darbepoetin alfa (DA) 500 µg administered once every 3 weeks (Q3W) has been shown to be effective in patients with chemotherapy-induced anaemia.. This non-interventional study investigated the efficacy and usage patterns of DA 500 µg Q3W in routine clinical practice.. Prospective data on adult anaemic cancer patients receiving DA 500 µg Q3W during chemotherapy was collected. Efficacy of DA treatment was measured as the red blood cell transfusion (RBCT) incidence, the change in Hb over time, hospitalisations for anaemia, and the change in Eastern Cooperative Oncology Group (ECOG) performance status between baseline and study end. Usage patterns were evaluated in Hb categories at baseline and week 16, DA dosage information, and adherence to the guidelines issued by the European Organisation for Research and Treatment of Cancer (EORTC).. A total of 309 patients were included. The median study duration was 16 weeks and the overall transfusion rate was 19%. Significantly fewer patients required transfusions when DA was initiated at Hb 9.0-10.0 g/dL (19%), as compared to later at a Hb < 9.0 g/dL (50%, p = 0.0002). Transfusion-independent patients had fewer anaemia-related hospitalisations and better ECOG scores at the end of the study. A total of 83% of patients reached a Hb ≥ 11.0 g/dL during weeks 1-16. Physicians' adherence to Hb thresholds for DA initiation as recommended by the EORTC was observed in 83% of patients.. In accordance with the recommended treatment objective for DA to minimise RBCTs, 81% of study patients remained free of RBCTs during DA 500 µg Q3W treatment and at an even higher rate if DA treatment was initiated before Hb fell below 9.0 g/dL.

Topics: Adult; Aged; Algorithms; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Withholding Treatment

To evaluate adherence to European Organisation for Research and Treatment of Cancer (EORTC) and European Summary of Product Characteristic (SmPC) guidance on recommended haemoglobin (Hb) values in routine clinical practice use of darbepoetin alfa (DA) in cancer patients internationally.. This multicentre, prospective, observational study assessed DA use in 11 European countries. This interim analysis (IA) included ∼1300 breast, colorectal, ovarian or lung cancer patients receiving DA during any chemotherapy cycle. Hb level and red blood cell (RBC) transfusion requirement data were collected.. Of the 1290 patients (mean [SD] age 62.5 [11.1] years) included in this IA full analysis set, 499 had lung, 387 breast, 192 colorectal and 212 ovarian cancer. Mean baseline Hb levels were <10 g/dL. At week 9, 426 (33%) patients had a Hb level of 10-12 g/dL, 165 (13%) of >12 g/dL, 226 (18%) of <10 g/dL and 473 (37%) had missing Hb values. 54% of the 672 patients still on the study at week 9 with available Hb values had Hb values of 10-12 g/dL. For patients with a baseline Hb of <10 g/dL, the Kaplan-Meier (K-M) percentage of patients with Hb levels ≥10 g/dL from week 1 to end of treatment period (EOTP) was 86%. For these patients, the K-M% of patients with Hb levels >13 g/dL from week 1 to EOTP was 10%. The K-M% of patients requiring RBC transfusions from week 5 to EOTP was 26% for all patients. Seven patients reported treatment-related non-serious adverse drug reactions, four were thromboses.. This IA suggests most patients were treated according to European SmPC guidance. Hb evolution during the study is consistent with data from clinical trials, implying DA is effective in increasing Hb levels in chemotherapy-induced anaemia patients. Hb levels >13 g/dL were infrequent. Limitations are related to the observational nature of this study.

Topics: Aged; Darbepoetin alfa; Erythrocyte Transfusion; Erythropoietin; Europe; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Time Factors

Mitomycin C (MC) is used as therapy against solid tumors, also combined with other chemotherapeutic agents or radiotherapy. It may cause acute, subacute, or chronic anemia capable of modifying the results of chemo- and radiotherapy. Erythropoietin may be lowered by cancer itself or because of chemoradiotherapy. There are few studies investigating the relationship between erythropoietin and chronic anemia.We prospectively analyzed the chronic anemia and erythropoietin in 38 patients with solid cancer. Patients were 40 to 82 years of age. MC was randomly given every 3 weeks as a single drug at 10 or 20 mg/m². When myelotoxicity occurred the next therapy cycle was delayed until recovery. RBC indices, hemolysis, erythropoietin, liver and kidney function were studied. MC cycles were 136 (3.6 ± 1.4 per pt), 32 being delayed because of myelotoxicity.Hematocrit, hemoglobin and RBC were inversely related to the cumulative dose (r = 0.70 to 0.86; p 0.03 to 0.01) of MC. Other tests remained stable. Anemia occurred almost twofold earlier in the 20 mg/m² group (p=0.049). basal erythropoietin, already lower than in age and sex watched 81 non cancerous subjects (p<0.001), decreased during MC therapy (p<0.01). For each given MC mg/m² a 0.0372 Hb mg/dl reduction occurred. Chronic anemia due to MC is accompanied by erythropoietin reduction. These results can help in designing chemoradiotherapy.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Chemoradiotherapy; Chronic Disease; Disease Progression; Dose-Response Relationship, Drug; Erythrocytes; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Male; Middle Aged; Mitomycin; Neoplasms; Prospective Studies

Anaemia during chemotherapy is often left untreated. Erythropoiesis-stimulating agents are frequently used to treat overt anaemia. Their prophylactic use, however, remains controversial and raises concerns about cost-effectiveness. Therefore, we assessed the efficacy of a dose-reduction schedule in anaemia prophylaxis.. The study included patients with untreated solid tumours about to receive platinum-based chemotherapy and had haemoglobin (Hb) levels ≥11 g/dL. Epoetin-α was administered at a dose level of 3 × 10,000 U weekly as soon as Hb descended to < 13 g/dL. Dose reductions to 3 × 4,000 U and 3 × 2,000 U weekly were planned in 4-week intervals if Hb stabilised in the range of 11-13 g/dL. Upon ascending to ≥13 g/dL, epoetin was discontinued. Iron supplements of 100 mg intravenous doses were given weekly. Of 37 patients who enrolled, 33 could be evaluated.. Their median Hb level was 13.7 (10.9-16.2) g/dL at baseline and descended to 11.0 (7.4-13.8) g/dL by the end of chemotherapy. Anaemia (Hb < 10 g/dL) was prevented in 24 patients (73%). The mean dose requirement for epoetin-α was 3 × 5,866 U per week per patient, representing a dose reduction of 41%. Treatment failed in nine patients (27%), in part due to epoetin-α resistance in four (12%) and blood transfusion in three (9%) patients.. Dose reduction was as effective as fixed doses in anaemia prophylaxis but reduced the amount of prescribed epoetin substantially.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins

The relationship between darbepoetin alfa and fatigue in chemotherapy-induced anemia (CIA) patients is complex because of patients receiving transfusions and the mediating effect of hemoglobin. Latent growth models (LGMs) were used to examine simultaneously relationships among drug exposure, fatigue outcomes, covariates, and mediating factors.. Data from four CIA studies (AMG 20010145: small cell lung cancer, n=547; AMG 980297: lung cancer, n=288; AMG 20000161: lymphoproliferative malignancies, n=339; AMG 20030232: non-myeloid malignancies, n=320) were analyzed separately. Patients reported fatigue using the FACT-Fatigue. The effect of darbepoetin alfa on FACT-F changes mediated through hemoglobin changes was examined with LGMs controlling for transfusions, age, sex, baseline ECOG performance status, and health status (EQ-5D VAS). Model fit was assessed using multiple indices including the comparative fit index (CFI).. Darbepoetin alfa increased hemoglobin levels which were associated with decreases in fatigue. Increases in hemoglobin were statistically significantly (p<0.05) related to decreases in fatigue in the studies (AMG 20030145: beta=0.28; AMG 980297: beta=0.46; AMG 20000161: beta=0.59; and AMG 20030232: beta=0.39). Darbepoetin alfa statistically significantly increased hemoglobin (AMG 20010145:beta=0.50, AMG 980297:beta=0.53, AMG 20000161:beta=0.47, and AMG 20030232:beta=0.30) while controlling for covariates. Model fit was acceptable (CFI> or =0.89) in all studies.. Results indicate LGMs may be a valuable statistical method for modeling complex relationships among clinical and patient reported outcomes. A statistically significant effect of darbepoetin alfa on fatigue change through hemoglobin change occurred across four studies, after modeling the effects of transfusions, age, sex, EQ-5D VAS and ECOG.

Topics: Anemia; Antineoplastic Agents; Area Under Curve; Darbepoetin alfa; Erythropoietin; Fatigue; Female; Health Status Indicators; Hematinics; Hemoglobins; Humans; Likelihood Functions; Male; Middle Aged; Models, Statistical; Multivariate Analysis; Neoplasms; Regression Analysis; Statistics as Topic

The aim of our study was to compare hemorheological consequences of hemotransfusion and recombinant human erythropoetin treatment in anemic cancer patients. Forty anemic patients with solid nonmyeloid malignancies were enrolled in this prospective, open-label study. Both prior to and following treatment (epoetin beta, 10,000 units subcutaneously thrice weekly, for four weeks and transfusion of 400 ml of erythrocyte mass) hemorheological measurements including blood and plasma viscosity, hematocrit (Hct), hemoglobin, red blood cell aggregation (RBCA) and deformability were completed. It was found an increase of Hb from 76.07+/-3.68 g/l to 87.86+/-4.26 g/l after the transfusion. It was accompanied by Hct rise by 25% (from 23.67+/-1.85 to 29.50+/-1.96%, p<0.05). Under these conditions the whole blood viscosity (BV) was increased by 19% (p<0.05). Plasma viscosity did not change markedly. Therefore the main cause of the whole blood viscosity rise was an increase of Hct. After erythrocyte mass transfusion there were some increases of red cell deformability and aggregation (by 7%, p>0.05). Under these conditions the Hct/BV ratio as an index of oxygen transport efficiency was changed after transfusion only slightly. While after four weeks of epoetin treatment the hematocrit/viscosity ratio was raised by 14% (p<0.05), in spite of the high blood viscosity. In addition RBCA decreased (p<0.01) and their deformability was increased by 14% (p<0.05). In vitro microrheological data permit to suggest that epoetin has a direct effect on the microrheological properties of red cells due to activation of the cellular signal transduction system including the tyrosine kinases and phosphatases. Thus, Epoetin beta administered s.c. thrice weekly, during four weeks, increased hemoglobin levels, improved hemorheological profile and especially its microrheological part as well as the blood transport capacity in anemic cancer patients who were receiving chemotherapy and its hemorheological effect was more positive than under hemotransfusion.

Topics: Anemia; Blood Transfusion; Blood Viscosity; Erythrocytes; Erythropoietin; Hemoglobins; Hemorheology; Humans; Middle Aged; Neoplasms; Pilot Projects; Prospective Studies; Recombinant Proteins; Signal Transduction

Evaluate efficacy and safety of epoetin beta in anaemic patients receiving chemotherapy for a non-myeloid malignancy.. This open-label, multicentric, clinical trial was conducted in France among 691 anaemic patients (haemoglobin < or = 12 g/dL) with a solid or haematological malignancy to evaluate the benefit of epoetin beta 30,000 IU/week subcutaneously for 16 weeks. The primary endpoint was the rate of therapeutic response.. The overall response rate was 60.4% (CI 95%: [56.6%-64.1]). According to initial haemoglobin level < 11 g/dL or between 11 and 12 g/dL, it was 61.2% and 57.5% respectively. Response rates by tumour type (solid and haematological) were similar. The mean haemoglobin level increases were respectively 1.1 g/dL, approximately 2 and 2.2 g/dL at 4, 9, and 12 weeks after treatment initiation. In patients with haemoglobin level < 11 g/dL at inclusion the mean increases in haemoglobin level were respectively 1.17, 2.03 and 2.45 g/dL at 4, 9 and 12 weeks. During study period, 23% of patients required red blood cell transfusion. Overall treatment with epoetin beta was well-tolerated and 7.1% of patients only experienced thromboembolic events.. For treating chemotherapy-induced anaemia in patients with solid or haematological malignancy (especially if haemoglobin level < 11 g/dL), epoetin beta 30.000 IU subcutaneously once-weekly (450 IU/kg/week) is rapidly effective and overall well-tolerated.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Drug Administration Schedule; Erythropoietin; Female; France; Hematinics; Hematologic Neoplasms; Hemoglobin A; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Recombinant Proteins; Young Adult

Advanced-stage cancer patients often suffer from anemia that closely resembles the anemia of chronic inflammatory diseases characterized by specific changes in iron homeostasis and absorption. i.v. iron improves the efficacy of recombinant human erythropoietin (rHuEPO) in anemic cancer patients undergoing chemotherapy. We report the results of an open-label, randomized, prospective trial aimed at testing the efficacy and safety of treatment with oral lactoferrin versus i.v. iron, both combined with rHuEPO, for the treatment of anemia in a population of 148 advanced cancer patients undergoing chemotherapy. All patients received s.c. rHuEPO-beta, 30,000 UI once weekly for 12 weeks, and were randomly assigned to ferric gluconate (125 mg i.v. weekly) or lactoferrin (200 mg/day). Both arms showed a significant hemoglobin increase. No difference in the mean hemoglobin increase or the hematopoietic response, time to hematopoietic response, or mean change in serum iron, C-reactive protein, or erythrocyte sedimentation rate were observed between arms. In contrast, ferritin decreased in the lactoferrin arm whereas it increased in the i.v. iron arm. In conclusion, these results show similar efficacy for oral lactoferrin and for i.v. iron, combined with rHuEPO, for the treatment of anemia in advanced cancer patients undergoing chemotherapy.

Topics: Administration, Oral; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Erythropoietin; Female; Ferric Compounds; Hemoglobins; Humans; Lactoferrin; Male; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins; Treatment Outcome

This study evaluated efficacy and safety of darbepoetin alfa administered every 3 weeks (Q3W) at fixed doses of 300 or 500 μg with or without intravenous (IV) iron in treating anemia in patients receiving multicycle chemotherapy. This Phase 2, double-blind, 2 × 2 factorial study randomized patients to one of four treatment arms; darbepoetin alfa 300 μg (n = 62), darbepoetin alfa 300 μg plus IV iron (n = 60), darbepoetin alfa 500 μg (n = 60), or darbepoetin alfa 500 μg plus IV iron (n = 60). Patients had nonmyeloid malignancies, hemoglobin levels ≤10 g dL(-1), and no iron deficiency. Primary endpoint was achievement of target hemoglobin (≥11 g dL(-1)). Secondary endpoints included incidence of transfusions and change in Functional Assessment of Cancer Therapy Fatigue (FACT-F) score from baseline to end of study. Safety was evaluated by incidence of adverse events. No evidence of a statistically significant interaction between darbepoetin alfa dose received and IV iron usage was observed, therefore, results are provided separately comparing darbepoetin alfa doses and comparing IV iron usage groups. Similar proportions of patients receiving darbepoetin alfa 300 or 500 μg achieved target hemoglobin (75 and 78%, respectively); Kaplan-Meier median time to target hemoglobin was 10 and 8 weeks, respectively. More patients receiving IV iron (82%) than not receiving IV iron (72%) achieved hemoglobin target. Adverse events profiles were similar for darbepoetin alfa treatment groups. Transient anaphylactoid reactions were reported in two patients receiving IV iron. Darbepoetin alfa at 300 μg Q3W and 500 μg Q3W showed similar benefit, while added IV iron improved treatment response in these patients.

Topics: Aged; Anemia; Darbepoetin alfa; Double-Blind Method; Erythropoietin; Female; Hemoglobins; Humans; Infusions, Intravenous; Iron; Male; Middle Aged; Neoplasms; Time Factors

Recombinant human erythropoietin (RHuEPO) is an erythropoiesis stimulating agent (ESA) used to treat anemia in patients with total or relative erythropoietin deficit. In cancer patients, it is administered to optimize hemoglobin (Hb) levels, correct anemia and reduce the need for transfusions. Cuba produces a RHuEPO, registered in 1998 as iorEPOCIM, that is widely used in the national public health system, mainly to treat patients with anemia due to chronic kidney disease (CKD).. Evaluate the efficacy and safety of iorEPOCIM in pediatric cancer patients with anemia following chemotherapy or radiotherapy. The working hypothesis posed an Hb increase>or=15 g/l in 70% of patients receiving iorEPOCIM for 8 weeks.. A Phase IV, multicenter, open clinical trial was conducted. Participants were 157 patients aged 1-19 years with anemia and cyto-histological diagnosis of cancer in any location. Patients received either 600 U/kg iorEPOCIM intravenously, once weekly, or 150 U/kg iorEPOCIM subcutaneously, 3 times a week, for 8 weeks. All patients had blood tests every week to determine hemoglobin and hematocrit, and reticulocyte and platelet counts. Mean number of transfusions required by patients during the treatment period was compared to the mean number of transfusions received in the preceding 8 weeks. Adverse events (AE) were recorded at the 4th and 8th weeks and classified by intensity and causality.. Hb levels rose>or=15 g/l in 68.8% of patients, and transfusion requirements decreased 17%. The most frequent adverse events were fever (19.3%), vomiting (10.2%) and flu-like syndrome (9.6%). Intensity of AE was predominantly mild. Only 7 AE were classified as very probably related to the product and none of those was severe.. iorEPOCIM proved to be safe and effective at the doses and frequencies used in this patient population. As a result, this medication was recommended for use in all pediatric oncology and hematology services in the country.

Topics: Adolescent; Anemia; Child; Child, Preschool; Cuba; Erythropoietin; Female; Humans; Infant; Male; Neoplasms; Radiation Injuries; Treatment Outcome; Young Adult

Chemotherapy-induced anemia (CIA) is responsive to treatment with erythropoiesis-stimulating agents (ESAs) such as darbepoetin alfa. Administration of ESAs on a synchronous schedule with chemotherapy administration could benefit patients by reducing clinic visits and potentially enhancing on-time chemotherapy delivery.. This phase 2, 25-week, open-label study evaluated the noninferiority of darbepoetin alfa administered weekly vs. as an extended dosing schedule (every 2 or 3 weeks) in patients with CIA. Patients were randomized 1:1 to an extended dosing schedule (EDS: darbepoetin alfa 300 μg Q2W if chemotherapy was QW, Q2W, or Q4W or darbepoetin alfa 500 μg Q3W if chemotherapy was Q3W) or weekly (150 μg QW regardless of chemotherapy schedule). Stratification factors included chemotherapy cycle length, screening hemoglobin (<10 g/dL vs. ≥10 g/dL), and tumor type (lung/gynecological vs. other nonmyeloid malignancies). The primary endpoint was change in hemoglobin from baseline to Week 13.. Seven hundred fifty-two patients (374 QW patients; 378 EDS patients) received ≥1 dose of darbepoetin alfa and were included in the analysis. Demographics and disease state were similar between groups. Seventy-one percent of patients in the EDS group and 76% in the QW group achieved the target hemoglobin of ≥11.0 g/dL. There was a minimal difference in the primary endpoint of mean change in hemoglobin (baseline to Week 13) between the QW and the EDS groups (-0.04 g/dL; 95% confidence interval: -0.26, 0.17 g/dL). The upper limit of the 95% confidence interval was less than the prespecified limit of <0.75 g/dL, supporting noninferiority of the EDS dosing schedule. Reported adverse events were similar between groups. A slight increase in transfusions was reported in the QW group.. Darbepoetin alfa, when administered synchronously with chemotherapy, on an EDS appears to be similarly efficacious to darbepoetin alfa weekly dosing with no unexpected adverse events. This study provides prospective data on how multiple dosing regimens available with darbepoetin alfa can be synchronized with chemotherapy administered across a range of dosing schedules.. ClinicalTrials.gov Identifier NCT00144131.

Topics: Activities of Daily Living; Aged; Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Administration Schedule; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Time Factors; Treatment Outcome

The subject of this study was the effect of erythropoetin (Epoetin) treatment of anemic patients (n=30) with solid tumors on parameters of hemorheological profile. Both prior to and following Epoetin treatment (10,000 units subcutaneously thrice weekly) for four weeks hemorheological measurements included plasma and red blood cell (RBC) suspension viscosity; high and low shear whole blood viscosity; hematocrit (Hct), hemoglobin, RBC aggregation (RBCA) and deformation. It was found that the patients had reduced Hb up to 92.96+/-2.99 g/l, and the Hct - 28.2%. These parameters were significant increased after four weeks of Epoetin treatment: Hb by 28% (p<0.01) and Hct by 31% (p<0.01). In macrorheological part of the profile, both the high shear blood viscosity, and the low one were increased by 23 and 27% (p<0.05), respectively. These changes were mainly associated with the Hct rise. As for microrheological part of profile after Epoetin treatment, RBCA was decreased by 25% (p<0.05). While the red cell rigidity index (Tk) was lowered only slightly (by 8%). RBC incubation with Epoetin (10.0 I.E./ml) was accompanied by 10% decrease of Tk. It is important to note that before Epoetin treatment incubation with it led to decrease of RBCA by 30% (p<0.05), whereas after four week of the treatment period a 27% (p<0.05) rise of aggregation was found in majority of patients. Thus these results suggest that Epoetin is an effective, safe and convenient therapy for the management of anaemia in patients with cancer. And this drug has a moderate positive hemorheological effect on RBC and on the microrheological properties in particular. These data suggested that Epoetin has an effect on the membrane properties regulating RBC aggregation and deformation and affects by the signal transduction system, including Ca2+-dependant signaling pathway and tyrosine kinase and phosphotase activity change.

Topics: Aged; Anemia; Case-Control Studies; Erythrocyte Aggregation; Erythrocyte Deformability; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins

Epoetin-alpha initiated once weekly, followed by once-every-3-weeks maintenance, was effective and well tolerated for chemotherapy-induced anemia. This study evaluated a starting dose of epoetin-alpha 120,000 U once every 3 weeks for chemotherapy-induced anemia using early and late initiation regimens.. Patients with baseline hemoglobin 11.0-12.0 g/dL were randomly assigned to early intervention with immediate epoetin-alpha (n = 68) or to standard intervention with epoetin-alpha when hemoglobin decreased to <11 g/dL (n = 68). A third group of patients with baseline hemoglobin <11 g/dL (n = 50) were enrolled but not randomized; epoetin-alpha was initiated immediately. The primary endpoint was mean proportion of hemoglobin values within the target range (11.0-13.0 g/dL) among randomized patients.. The mean proportion of hemoglobin values in range through week 16 was 60% in each randomized group. Mean hemoglobin by week showed similar increases over the study. Blood transfusions were administered in 9%, 8%, and 24% of patients in the early, standard, and nonrandomized groups. Mean epoetin-alpha doses were similar between treatment groups. Dose reductions and withholds were more common in the early intervention group. Adverse events (eg, diarrhea, fatigue, nausea) were consistent with the safety profile for epoetin-alpha . Clinically relevant thrombotic vascular events (regardless of relationship to study treatment) were reported for 9%, 12%, and 12% of patients in the early, standard, and nonrandomized groups.. Early and standard intervention with epoetin-alpha, administered once every 3 weeks, increased and maintained hemoglobin levels within 11.0-13.0 g/dL in patients with chemotherapy-induced anemia.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Blood Transfusion; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins

Epoetin (EPO) administration reduces the need for transfusion. Identifying patients at high risk of anemia requiring red blood cell (RBC) transfusion is needed. This multicentric phase III trial tested epoetin alpha (EPOalpha) administration according to our risk model on the basis of three clinical parameters: hemoglobin (Hb) <12 g/dl, lymphocytes 1.. Patients >or=18 years with chemotherapy-treated solid or hematologic tumors were randomized to 150 UI/kg/TIW s.c. EPOalpha (arm 1) or no EPOalpha (arm 2) and stratified on Hb level at day 0, lymphocyte count, and PS. The primary end point was transfusion rate; secondary end points included overall survival (OS), safety, and quality of life.. From September 2000 to January 2005, 218 patients (median age 64 years, 42.7% males) with principally breast cancer, sarcoma, or lung carcinoma were included. In total, 93% patients had PS >1 and 35% had

Topics: Adult; Aged; Aged, 80 and over; Anemia; Chemoprevention; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Models, Biological; Neoplasms; Prospective Studies; Recombinant Proteins; Risk Factors

To explore the efficacy and mechanism of Yixuesheng capsule (, YXS) combined with recombination human erythropoietin (RHE) in treating male neoplastic anemia (NA).. Sixty-five patients were randomized into two groups, the 33 patients in the treated group treated with a combined therapy of YXS and RHE, and the 32 in the control group treated with RHE alone, all for 12 weeks. Related clinical indexes, including hemoglobin (Hgb), red blood cell (RBC), hematocrit (HMC), testosterone (T), estradiol (E(2)) and prolactin (PRL), were measured before and after treatment.). After treatment, Hgb in the treated group and the control group was 108+/-5 g/L and 104+/-8 g/L respectively, showing marked improvement as compared with that before treatment (P<0.01), and the improvement in the former was more significant than that in the latter (P<0.05). Further, the level of T was also increased in the treated group after treatment (P<0.05), and showed a significant difference from that of the control group (P<0.05).. YXS capsule combined with RHE shows a better therapeutic effect in treating NA than that of RHE alone, and the effect might be through stimulation by YXS of erythropoiesis which could promote the secretion of testosterone.

Topics: Adult; Aged; Anemia; Capsules; Drug Therapy, Combination; Drugs, Chinese Herbal; Erythrocytes; Erythropoietin; Gonadal Steroid Hormones; Hematocrit; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Treatment Outcome

Erythropoietin corrects and prevents anemia and decreases the need for red blood cell (RBC) transfusions; its impact on quality of life (QOL) of cancer patients receiving chemotherapy is not clear.. 399 patients with solid tumors and Hb level of < or = 12 g/dl receiving chemotherapy were randomized to receive or not 10,000 IU epoetin-alpha thrice weekly. QOL was measured by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale and various subscales at baseline, at two months and at the end of the study.. Changes in the average QOL scores were similar in the two groups. The improvement in Hb levels was significantly higher for the epoetin-alpha group, with a decrease in transfusion requirements compared to the control group.. Epoetin-alpha does not improve QOL of patients with solid tumors receiving chemotherapy as assessed using FACT-An scale and various subscales, despite improving Hb levels and reducing transfusion requirements.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Organoplatinum Compounds; Quality of Life; Recombinant Proteins; Treatment Outcome; Young Adult

Recombinant human epoetin alfa, HX575, is the first biosimilar erythropoiesis-stimulating agent (ESA) with European marketing authorisation. The primary objective of this double-blind, randomised, multicentre study was to assess the efficacy and safety of HX575 in treating chemotherapy-associated symptomatic anaemia in patients with solid tumours.. The patients (n = 114) were treated with HX575 or active control (epoetin alfa) at 150 IU/kg body weight 3 times weekly for 12 weeks, increased to 300 IU/kg body weight 3 times weekly if the haemoglobin/reticulocyte increase was insufficient after 4 or 8 weeks.. With HX575, haemoglobin increased by > or =20 g/l in 62% (37/60 patients). The confidence interval (48.2%, 73.9%) was entirely above the pre-defined 30% threshold. Both groups showed similar results for safety profiles and secondary efficacy parameters. Transfusion requirements were 32% (19/60) (HX575) and 38% (13/34) (epoetin alfa).. In treating chemotherapy-associated symptomatic anaemia in patients with solid tumours, the biosimilar ESA, HX575, is efficacious with a safety profile as expected for the therapeutic area.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Female; Germany; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Single-Blind Method; Treatment Outcome

To perform an open, non-controlled, multiple-dose, international, multicentre, phase III study to evaluate epoetin zeta, a biosimilar epoetin referenced to epoetin alfa, for the treatment of chemotherapy-induced anaemia in patients with cancer.. Safety, tolerability and efficacy of subcutaneously administered epoetin zeta were assessed in 216 patients with solid tumours or non-myeloid haematological malignancies receiving chemotherapy and at risk of transfusion.. A significant (p < 0.0001) increase in mean haemoglobin (Hb) level (1.8 g/dL) was observed between baseline and week 12 (intent-to-treat population); 176/216 (81.5%) patients achieved a response (increase in Hb > or = 1 g/dL or reticulocyte count > or = 40,000 cells/microL) by week 8. Over the treatment period, 231 treatment-emergent adverse events were experienced by 91 patients; 9/216 (4.2%) experienced a clinically significant thrombotic event within the first 12 weeks of epoetin zeta treatment, significantly lower than the assumed 18% baseline incidence (p < 0.0001) based on historical data from epoetin trials. No transfusion was necessary for 175/216 patients (81.0%) and quality of life improved over the study. No patients developed anti-erythropoietin antibodies. Sponsor trial no: CT-830-05-0009.. This study demonstrates that subcutaneously administered epoetin zeta is well-tolerated and has efficacy in the treatment of anaemia in patients with cancer receiving chemotherapy and at risk of transfusion.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Anemia; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Treatment Outcome; Young Adult

Darbepoetin alfa is effective in treating chemotherapy-induced anemia (CIA). Administration of subcutaneous darbepoetin alfa every 3 weeks (Q3W) could simplify treatment through synchronization with common Q3W chemotherapy regimens. We report results from a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy and safety of fixed-dose Q3W darbepoetin alfa in patients with a wide variety of tumor types who experienced CIA.. Patients aged > or = 18 years with anemia (hemoglobin <11 g/dL) being treated for nonmyeloid malignancy were randomized 1:1 to receive darbepoetin alfa 300 microg (n = 193) or placebo (n = 193) subcutaneously Q3W from weeks 1 to 13 in this 16-week study. Doses could be adjusted per prespecified rules.. The primary endpoint was the proportion of patients who received > or =1 red blood cell (RBC) transfusion between week 5 and the end of the treatment period (EOTP). The study also analyzed the proportions of patients achieving a hemoglobin concentration > or =11 g/dL and subsequently maintaining hemoglobin levels above 11 g/dL, and the change in hemoglobin concentration over time.. The proportion of patients requiring RBC transfusions between week 5 and EOTP was significantly lower in the darbepoetin alfa-treated group than in the placebo-treated group (24 vs. 41% of patients, a 16.3% difference, p < 0.001). There were no differences between the two treatment arms in quality-of-life measures. Cardiovascular/thromboembolic adverse events were uncommon and were not associated with increases in hemoglobin levels. Study limitations suggest caution in the interpretation of these results: transfusions, the primary endpoint, were recommended but not required if hemoglobin concentrations were < or =8.0 g/dL, and protocol deviations (primarily dosing errors) occurred in approximately one-half of the patients in both treatment groups.. In this study, fixed-dose Q3W darbepoetin alfa appeared to be well-tolerated and effective for the treatment of CIA.. Study 20030232; ClinicalTrials.Gov Identifier: NCT00110955.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Anemia; Antineoplastic Combined Chemotherapy Protocols; Darbepoetin alfa; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Placebos; Young Adult

Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease. Although darbepoetin alfa can effectively increase hemoglobin levels, its effect on clinical outcomes in these patients has not been adequately tested.. In this study involving 4038 patients with diabetes, chronic kidney disease, and anemia, we randomly assigned 2012 patients to darbepoetin alfa to achieve a hemoglobin level of approximately 13 g per deciliter and 2026 patients to placebo, with rescue darbepoetin alfa when the hemoglobin level was less than 9.0 g per deciliter. The primary end points were the composite outcomes of death or a cardiovascular event (nonfatal myocardial infarction, congestive heart failure, stroke, or hospitalization for myocardial ischemia) and of death or end-stage renal disease.. Death or a cardiovascular event occurred in 632 patients assigned to darbepoetin alfa and 602 patients assigned to placebo (hazard ratio for darbepoetin alfa vs. placebo, 1.05; 95% confidence interval [CI], 0.94 to 1.17; P=0.41). Death or end-stage renal disease occurred in 652 patients assigned to darbepoetin alfa and 618 patients assigned to placebo (hazard ratio, 1.06; 95% CI, 0.95 to 1.19; P=0.29). Fatal or nonfatal stroke occurred in 101 patients assigned to darbepoetin alfa and 53 patients assigned to placebo (hazard ratio, 1.92; 95% CI, 1.38 to 2.68; P<0.001). Red-cell transfusions were administered to 297 patients assigned to darbepoetin alfa and 496 patients assigned to placebo (P<0.001). There was only a modest improvement in patient-reported fatigue in the darbepoetin alfa group as compared with the placebo group.. The use of darbepoetin alfa in patients with diabetes, chronic kidney disease, and moderate anemia who were not undergoing dialysis did not reduce the risk of either of the two primary composite outcomes (either death or a cardiovascular event or death or a renal event) and was associated with an increased risk of stroke. For many persons involved in clinical decision making, this risk will outweigh the potential benefits. (ClinicalTrials.gov number, NCT00093015.)

Topics: Aged; Anemia; Cardiovascular Diseases; Darbepoetin alfa; Diabetes Mellitus, Type 2; Double-Blind Method; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Middle Aged; Neoplasms; Renal Insufficiency, Chronic; Stroke

This study aimed to provide further clinical evidence for the efficacy and safety of epoetin beta once weekly across a wide range of cancer types.. This was a multicenter, open-label, prospective, single-arm study in patients with either a solid tumor or non-myeloid hematological malignancy, receiving or scheduled to receive further chemotherapy. Patients received epoetin beta 30,000 IU subcutaneously once weekly for 16 weeks. The primary efficacy endpoint was the change in hemoglobin (Hb) level according to the patient's baseline Hb level.. A total of 691 patients were included in the intent-to-treat population. Epoetin beta effectively increased Hb levels (a mean increase from baseline of 1.1 g/dl by week 4 and 2.2 g/dl by week 12). Hb response was achieved in 60.4% of all patients and 61.2% of those with baseline Hb <11 g/dl. Hb response was similar in patients with solid tumors (60.5%) and non-myeloid hematological malignancies (60.2%). Type of chemotherapy and baseline platelet count were independent predictive factors for response. Epoetin beta treatment was well tolerated.. Epoetin beta 30,000 IU once weekly effectively increases Hb levels, is well tolerated and has similar efficacy in anemic patients with solid tumors or non-myeloid hematological malignancies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Erythropoietin; Female; Hematinics; Hematologic Neoplasms; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Recombinant Proteins

Darbepoetin alfa is an erythropoiesis-stimulating agent (ESA) approved for treating chemotherapy-induced anemia. This phase II, double-blind, placebo-controlled study examined the efficacy of darbepoetin alfa for treating anemia of cancer (AoC) in patients not receiving chemotherapy or radiotherapy. Patients were randomized 3:1 to receive darbepoetin alfa (6.75 microg/kg) or placebo every 4 weeks; the end of the study was at week 17. The primary endpoint was the percentage of patients with a hematopoietic response. Secondary endpoints included transfusion incidence and safety parameters. Efficacy analyses were performed on 162 patients in the darbepoetin alfa group and 56 patients in the placebo group. The Kaplan-Meier percentages of patients who achieved a hematopoietic response (darbepoetin alfa, 69%; placebo, 24%) or achieved the target hemoglobin (darbepoetin alfa, 85%; placebo, 50%) differed significantly between treatment groups. The transfusion incidence did not differ between treatment groups probably because of the low baseline transfusion rates in AoC patients. The incidence of adverse events (including on-study deaths) was similar in both groups. In conclusion, darbepoetin alfa appeared to be well tolerated and significantly increased hemoglobin levels in these AoC study patients.

Topics: Aged; Anemia; Blood Transfusion; Darbepoetin alfa; Double-Blind Method; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Neoplasms; Placebos; Safety; Survival Rate; Time Factors; Treatment Outcome

Functional iron deficiency is one reason for lack of response to erythropoietin treatment. Concomitant intravenous (IV) iron supplementation has the potential to improve response to erythropoietin, allowing a decrease in erythropoietin dose requirements. In a recent study of anaemic, iron-replete patients with lymphoproliferative malignancies (Leukemia, 21, 2007, 627), the haemoglobin (Hb) increase and response rate were significantly greater in patients receiving epoetin beta with concomitant IV iron compared with patients receiving epoetin beta without IV iron (P < 0.05). The present analysis aimed to investigate whether a combination of epoetin beta and IV iron is cost-effective compared with epoetin beta without IV iron.. This analysis was performed from a Swedish societal perspective as a within-trial evaluation of overall costs (based on differences in drug costs and resource use between groups) and effect (differences in Hb increases) during 16 weeks' treatment with epoetin beta with or without concomitant IV iron.. There was an improved response to epoetin beta with IV iron therapy and an almost 2-fold greater increase in Hb levels. Overall mean cost per patient in the epoetin beta with IV iron group was euro5558 and in the epoetin beta without IV iron group was euro6228. Thus, treatment with epoetin beta with IV iron resulted in overall cost savings of about 11% compared with epoetin beta without iron, mainly due to reduced erythropoietin dosages.. Epoetin beta with concomitant IV iron in anaemic patients with lymphoproliferative malignancies not receiving chemotherapy resulted in better outcomes at lower cost compared with epoetin beta without iron. This suggests that epoetin beta with IV iron is a dominant therapy from a Swedish perspective.

Topics: Aged; Aged, 80 and over; Anemia; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Costs; Drug Therapy, Combination; Erythropoietin; Female; Hemoglobins; Humans; Injections, Intravenous; Iron Compounds; Lymphoproliferative Disorders; Male; Middle Aged; Neoplasms; Recombinant Proteins; Sweden

This study was conducted to develop a brief measure of fatigue and functional impact in cancer patients with anemia.. Data were obtained from a multisite, phase 2 study of darbepoetin-alpha (n = 1,558). Eligible patients were >or=18 years with nonmyeloid malignancies and anemia (hemoglobin

Topics: Adult; Aged; Aged, 80 and over; Anemia; Clinical Trials, Phase II as Topic; Darbepoetin alfa; Erythropoietin; Fatigue; Female; Hematinics; Humans; Male; Middle Aged; Multicenter Studies as Topic; Neoplasms; Predictive Value of Tests; Quality of Life; Sickness Impact Profile; Surveys and Questionnaires

To assess the effect of epoetin delta on anaemia in patients with cancer who were receiving chemotherapy.. This report includes data from two 12-week studies of epoetin delta: a randomised, double-blind, placebo-controlled study of three times weekly epoetin delta (150 or 300IU/kg) and an open-label extension collecting further efficacy and safety information, in which patients initially received epoetin delta 150IU/kg. Co-primary end points for the double-blind study were an increase in haemoglobin levels and a reduction in the requirement for red blood cell transfusions compared with placebo.. Double-blind study: 313 cancer patients were randomised to epoetin delta or placebo. Epoetin delta was associated with a significantly greater increase in haemoglobin levels from baseline compared with placebo (epoetin delta 150 and 300IU/kg vs placebo: 2.5 and 2.5g/dl vs 0.6g/dl; P<0.0001 for both comparisons), meeting one co-primary end point. However, there were no significant differences between groups in the proportion of patients requiring red blood cell transfusions (epoetin delta 150 and 300IU/kg vs placebo: 26.0 and 21.9% vs 26.9%), the second co-primary end point. Open-label study: 149 patients entered the extension study. During the extension, haemoglobin levels were maintained and a higher proportion of patients who previously received placebo required transfusions than those who had previously received epoetin delta (previous epoetin delta 150 and 300IU/kg: 7.1 and 11.4% vs previous placebo: 15.9%). Adverse events were as expected for this population in both studies.. Epoetin delta shows potential as a treatment for anaemia in cancer patients receiving chemotherapy.

Topics: Anemia; Antineoplastic Agents; Double-Blind Method; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Safety

Anaemia is common in patients receiving chemotherapy, causing symptoms that have a major impact on quality of life (QoL). Epoetin beta rapidly increases haemoglobin (Hb) levels and improves QoL in anaemic patients with a variety of tumours. This was a randomized, double-blind, parallel-group, dose-finding study assessing the efficacy and safety of once-weekly epoetin beta in patients with solid tumours receiving chemotherapy. Adult patients with anaemia (Hb < 11 g/dL) were randomized to receive epoetin beta 30,000 IU or 20,000 IU once weekly for 12 weeks. All patients received oral iron supplementation. Haemoglobin levels, transfusion need and QoL [Functional Assessment of Cancer Therapy-fatigue (FACT-F) subscale score] were assessed at regular intervals. Fifty patients were randomized; 30 patients received epoetin beta 30,000 IU once weekly and 20 received 20,000 IU once weekly. Mean (+/- SD) increase in Hb from baseline to week 12 was 1.75 +/- 2.15 g/dL in the 30,000 IU group (P = 0.008 vs. baseline) and 1.04 +/- 1.75 g/dL in the 20,000 IU group (non-significant). Haemoglobin response (increase in Hb >or=2 g/dL from baseline) was observed in 78.3% of patients receiving epoetin beta 30,000 IU and 66.7% receiving epoetin beta 20,000 IU. Improvements in FACT-F subscale score were significantly (P < 0.001) correlated with increases in Hb level. Transfusion use was low during the study in both groups. Both epoetin beta regiments were well tolerated and there were no dose-dependent adverse events. Epoetin beta 30,000 IU once weekly is an effective and well-tolerated treatment of anaemia in patients with solid tumours.

Topics: Adult; Aged; Anemia; Double-Blind Method; Drug Administration Schedule; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins; Treatment Outcome

Anaemia is common in cancer patients treated with chemotherapy. Darbepoetin alfa (DA) is the only erythropoiesis-stimulating protein approved for administration at weekly and every-three-week intervals in cancer patients receiving chemotherapy. This article investigates the effectiveness, tolerability and effect on fatigue of DA.. Prospective, observational study performed in 30 Spanish centres. Eligible patients were > or = 18 years of age, anaemic (haemoglobin [Hb] < or = 11 g/dL), with non-myeloid malignancies, receiving chemotherapy. DA (150 mug) was administered weekly for a maximum of 16 weeks (dosage doubled if Hb increased < 1 g/dL after 4 weeks).. Haematopoietic response (Hb increase > or = 2 g/dL or Hb > or = 12 g/dL in the absence of transfusions in the previous 28 days), transfusion required between Weeks 5 and 16 and fatigue measured by the Fatigue subscale of the Functional Assessment of Cancer Therapy.. 293 adults were recruited (56.4% women), with lymphoproliferative malignancies (44.3%) or solid tumours (55.7%). Baseline Hb was 9-11 g/dL in 83.7% of patients. Sixty-four per cent (95% CI: 58.1-69.4%) had a haematopoietic response and 12% required transfusions. After adjusting for performance status, concomitant diseases and chemotherapy type, an increase in Hb level was significantly associated with an improvement in Fatigue subscale (+1.9 points per 1 g/dL). Only 2% of patients had treatment-related adverse events: thromboembolic pulmonary disease (0.3%); hypersensitivity reaction (0.3%); local pain following DA administration (0.3%); insomnia (0.3%); thrombocytosis (0.3%) and deep vein thrombosis (0.3%).. Fixed-dose DA administered once weekly seems to be an effective, well-tolerated treatment for chemotherapy-induced anaemia in patients with non-myeloid malignancies, and there is an indication of a possible benefit on fatigue in the clinical practice.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Darbepoetin alfa; Erythropoiesis; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Time Factors

Anemia in patients with solid tumors is a common problem that is associated with impaired exercise capacity, increased fatigue, and lower quality of life (QoL). Erythropoiesis-stimulating agents (ESAs) have been shown to improve these outcomes; however, it is unknown if additional benefits can be achieved with aerobic exercise training.. We conducted a single-center, prospective, randomized, controlled trial in 55 mild-to-moderately anemic patients with solid tumors. Patients were randomized to either darbepoetin alfa alone (DAL, n = 29) or darbepoetin alfa plus aerobic exercise training (DEX; n = 26). The DEX group performed aerobic exercise training three times per week at 60%-100% of baseline exercise capacity for 12 weeks. The primary endpoint was QoL assessed by the Functional Assessment of Cancer Therapy-Anemia scale. Secondary endpoints were fatigue, cardiorespiratory fitness (VO(2peak)), hemoglobin (Hb) response, and darbepoetin alfa dosing.. Intention-to-treat analyses indicated significant improvements in QoL and fatigue in both groups over time but there were no between-group differences. The DEX group had a significantly greater VO(2peak) than the DAL group (mean group difference, +3.0 ml/kg per minute; 95% confidence interval, 1.2-4.7; p = .001) and there were borderline significant differences in favor of the DEX group for Hb response and darbepoetin alfa dosing.. Aerobic exercise training did not improve QoL or fatigue beyond the established benefits of DAL but it did result in favorable improvements in exercise capacity and a more rapid Hb response with lower dosing requirements. Our results may be useful to clinicians despite the more recent restrictions on the indications for ESAs.

Topics: Adult; Aged; Anemia; Darbepoetin alfa; Double-Blind Method; Erythropoietin; Exercise; Exercise Therapy; Female; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Surveys and Questionnaires; Treatment Outcome

The aim of the study was to evaluate the effectiveness, safety, and clinical outcomes of erythropoietin therapy in the treatment of anaemic cancer subjects receiving chemotherapy and to examine hypochromic red blood cell measurement as an indicator of functional iron sufficiency and as a predictor of responsiveness or non-responsiveness to erythropoietin therapy.. Patients who had a non-myeloid malignancy, had Hb < or = 11.0 g/dL, had a life expectancy of more than 6 months, were 18 years or older, were receiving chemotherapy and would continue to be treated for at least 2 months were given s.c. epoetin alfa three times a week.. Haemoglobin levels increased significantly at all time periods compared with baseline and the number of transfusions received decreased significantly at all time periods compared with baseline. Quality of life as measured by Functional Assessment of Cancer Therapy-Anaemia showed significant increases at months 2 and 4 and there were significant improvements in the fatigue subscale at both time points (P < 0.05). Significant improvements at end-point were observed for the physical, emotional and functional well-being, and additional concern subscales (all P < 0.05). Haematocrit and reticulocytes increased significantly at end-point compared with at baseline (haematocrit 33.4 vs 28.3%, P < 0.001; reticulocytes 105.8 vs 78.6 x 10(9)/dL, P = 0.005). The percentage of hypochromic red blood cells did not show predictive value for response to treatment status.. Epoetin alfa improved haemoglobin levels and quality of life in anaemic cancer patients receiving chemotherapy.

Topics: Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Australia; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; New Zealand; Predictive Value of Tests; Prospective Studies; Recombinant Proteins; Time Factors; Treatment Outcome

Recombinant erythropoietin (rhEPOalpha) corrects anaemia, improves physical functioning and quality of life in cancer patients. However, published reports have suggested risks for tumour stimulation by provision EPO to patients with remaining tumour cells perhaps related to the presence of EPO receptor protein in tumour tissue. Therefore, the aim of the present study was to exclude a possibility that cancer patients who respond favourably to EPO treatment have mainly tumours with low EPO receptor protein expression.. Tumour tissue was evaluated in 87 patients out of 108 randomly allocated for treatment with rhEPOalpha (n = 50) versus controls (n = 58). Tumour cell proliferation (Ki-67 index) and EPO receptor protein expression were evaluated by immunohistochemistry.. EPO treatment varied between 2 and 35 months, in doses between 10,000 and 40,000 Units/week. Ki-67 index did not differ between study and control patients before EPO treatment. Tumour tissue erythropoietin receptor protein was also similar between treated and untreated patients. Around 40% of tumour cells contained EPO receptors. Survival did not differ among EPO treated and control patients analysed as intention to treat, while survival was significantly improved in EPO treated patients per protocol treatment (P < 0.05). Ki-67 index and tumour tissue erythropoietin receptor protein did not predict survival, which systemic inflammation (ESR) did (P < 0.02).. Our results support that reported risk to accelerate disease progression by EPO treatment in palliative care is not justified in patients with solid, gastrointestinal cancer despite tumour presence of EPO receptor protein.

Topics: Anemia; Erythropoietin; Female; Humans; Ki-67 Antigen; Male; Neoplasms; Palliative Care; Receptors, Erythropoietin; Recombinant Proteins

The efficacy and safety of darbepoetin alpha (DA) for treating patients with active cancer and anemia not receiving or planning to receive cytotoxic chemotherapy or myelosuppressive radiotherapy was evaluated.. Patients with active cancer and anemia not receiving or planning to receive chemotherapy or radiotherapy were enrolled onto a phase III, multicenter, randomized, placebo-controlled study and administered placebo or DA 6.75 microg/kg every 4 weeks (Q4W) for up to 16 weeks with a 2-year follow-up for survival. Patients who completed 16 weeks of treatment could receive the same treatment as randomized Q4W for an additional 16 weeks. The primary end point was all occurrences of transfusions from weeks 5 through 17; safety end points included incidence of adverse events and survival.. The incidence of transfusions between weeks 5 and 17 was lower in the DA group but was not statistically significantly different from that of placebo. DA was associated with an increased incidence of cardiovascular and thromboembolic events and more deaths during the initial 16-week treatment period. Long-term survival data demonstrated statistically significantly poorer survival in patients treated with DA versus placebo (P = .022). This effect varied by baseline covariates including, sex, tumor type, and geographic region; statistical significance diminished (P = .12) when the analysis was adjusted for baseline imbalances or known prognostic factors.. DA was not associated with a statistically significant reduction in transfusions. Shorter survival was observed in the DA arm; thus, this study does not support the use of erythropoiesis-stimulating agents in this subset of patients with anemia of cancer.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Combined Modality Therapy; Darbepoetin alfa; Double-Blind Method; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Placebos; Radiotherapy Dosage; Survival Rate

This study compared the effects of early intervention with standard use of epoetin alfa on haemoglobin (Hb) levels and transfusion requirements in cancer patients receiving chemotherapy. Patients with Hb>10 and < or= 12 g/dL were randomised 1:1 to epoetin alfa (40,000 IU, subcutaneously, once weekly), initiated within 7d of the start of the first on-study chemotherapy cycle (defined as early intervention) versus epoetin alfa when Hb

Topics: Adolescent; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Survival Analysis; Treatment Outcome

The concomitant use of intravenous (IV) iron as a supplement to erythropoiesis-stimulating agents in patients with chemotherapy-induced anemia is controversial. This study was designed to evaluate the efficacy and safety of darbepoetin alpha given with IV iron versus with local standard practice (oral iron or no iron).. In this multicenter, randomized, open-label, phase III study, 396 patients with nonmyeloid malignancies and hemoglobin (Hb) less than 11 g/dL received darbepoetin alpha 500 microg with (n = 200) or without (n = 196) IV iron once every 3 weeks (Q3W) for 16 weeks.. The hematopoietic response rate (proportion of patients achieving Hb >or= 12 g/dL or Hb increase of >or= 2 g/dL from baseline) was significantly higher in the IV iron group: 86% versus 73% in the standard practice group (difference of 13% [95% CI, 3% to 23%]; P = .011). Fewer RBC transfusions (week 5 to the end of the treatment period) occurred in the IV iron group: 9% versus 20% in the standard practice group (difference of -11% [95% CI, -18% to -3%]; P = .005). Both treatments were well tolerated with no notable differences in adverse events. Serious adverse events related to iron occurred in 3% of patients in the IV iron group and were mostly gastrointestinal in nature.. Addition of IV iron to darbepoetin alpha Q3W in patients with chemotherapy-induced anemia was well tolerated, resulting in an improved hematopoietic response rate and lower incidence of transfusions compared with darbepoetin alpha alone.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Therapy, Combination; Erythropoietin; Female; Hematinics; Humans; Infusions, Intravenous; Iron; Male; Middle Aged; Neoplasms; Treatment Outcome

Unresponsiveness to erythropoiesis-stimulating agents, occurring in 30% to 50% of patients, is a major limitation to the treatment of chemotherapy-related anemia. We have prospectively evaluated whether intravenous iron can increase the proportion of patients with chemotherapy-related anemia who respond to darbepoetin.. Between December 2004 and February 2006, 149 patients with lung, gynecologic, breast, and colorectal cancers and >or= 12 weeks of planned chemotherapy were enrolled from 33 institutions. Patients were required to have hemoglobin or= 12 g/dL or >or= 2 g/dL increase).. Hematopoietic response by intention-to-treat analysis was 76.7% (95%CI, 65.4% to 85.8%) in the darbepoetin/iron group and 61.8% (95%CI, 50.0% to 72.7%) in the darbepoetin group (P = .0495). Among patients fulfilling eligibility criteria and having received at least four darbepoetin administrations, hematopoietic responses in the darbepoetin/iron group (n = 53) and in the darbepoetin-only group (n = 50) were 92.5% (95% CI, 81.8% to 97.9%) and 70% (95% CI, 55.4% to 82.1%), respectively (P = .0033). Increase of hemoglobin during treatment period showed a time profile favoring darbepoetin/iron with statistically significant effect from week 5 on. The safety profile was comparable in the two arms.. In patients with chemotherapy-related anemia and no iron deficiency, IV iron supplementation significantly reduces treatment failures to darbepoetin without additional toxicity.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Erythropoietin; Female; Hematinics; Humans; Infusions, Intravenous; Iron; Male; Neoplasms

Anaemia is common during platinum-based chemotherapy. This study aimed to evaluate the efficacy and safety of epoetin beta in the prevention of severe anaemia in patients with solid tumours receiving concomitant platinum therapy.. In this open-label, single-arm study, patients (n = 255) with solid tumours and haemoglobin (Hb) levels 1 g/dl from baseline) plus patients whose Hb levels remained +/- 1 g/dl of baseline throughout the study] was observed in 234 patients (92%). Response to epoetin beta was rapid. Of the 159 patients achieving a Hb response, 139 (87%) had Hb levels > 1 g/dl of baseline within 4 weeks of treatment initiation. Mean Hb levels had improved from 10.8 +/- 1.0 g/dl at baseline to 12.2 +/- 1.8 g/dl by the final visit. Quality of life measured by linear analogue scale assessment significantly (P < 0.01) improved in patients achieving a Hb response (n = 159).. Epoetin beta effectively prevents anaemia in most patients with solid tumours receiving concurrent platinum-based chemotherapy.

Topics: Activities of Daily Living; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Iron; Male; Middle Aged; Neoplasms; Organoplatinum Compounds; Quality of Life; Recombinant Proteins

To evaluate the safety and efficacy of intravenous (IV) sodium ferric gluconate complex (FG), oral ferrous sulfate, or no iron to increase hemoglobin (Hb) in anemic cancer patients receiving chemotherapy and epoetin alfa.. In this open-label, multicenter trial, 187 patients with chemotherapy-related anemia (Hb <11 g/dl; serum ferritin > or =100 ng/ml or transferrin saturation > or =15%) scheduled to receive chemotherapy and epoetin alfa (40,000 U subcutaneously weekly) were randomized to 8 weeks of 125 mg of IV FG weekly, 325 mg of oral ferrous sulfate three times daily, or no iron. The primary outcome was a change in Hb from baseline to endpoint, first whole-blood or red blood cell transfusion, or study withdrawal.. One hundred twenty-nine patients were evaluable for efficacy (FG, n = 41; oral iron, n = 44; no iron, n = 44). Mean increase in Hb was 2.4 g/dl (95% confidence interval [CI], 2.1-2.7) for FG (p = .0092 vs. oral iron; p = .0044 vs. no iron), 1.6 g/dl (95% CI, 1.1-2.1) for oral iron (p =.7695 vs. no iron), and 1.5 g/dl (95% CI, 1.1-1.9) for no iron. Hb response (increase > or =2 g/dl) was 73% for FG (p = .0099 vs. oral iron; p = .0029 vs. no iron), 46% for oral iron (p = .6687 vs. no iron), and 41% for no iron. FG was well tolerated.. For cancer patients with chemotherapy-related anemia receiving epoetin alfa, FG produces a significantly greater increase in Hb and Hb response compared with oral iron or no iron, supporting more aggressive treatment with IV iron supplementation for these patients.

Topics: Administration, Oral; Aged; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Female; Ferric Compounds; Hematinics; Humans; Iron; Male; Middle Aged; Neoplasms; Prospective Studies; Recombinant Proteins

Anemia is frequently associated with cancer due to the disease itself and antineoplastic treatments. This open-label, uncontrolled, multi-center study evaluated the effects of once-weekly (qw) epoetin alfa 40,000 IU on hemoglobin (Hb) levels and quality of life (QoL) in anemic patients receiving chemotherapy for solid tumors.. A total of 522 patients with Hb level < or =12 g/dL received epoetin alfa 40,000 IU qw subcutaneously for 9-20 weeks to reach and maintain Hb range of 12-14 g/dL. QoL was assessed with the Functional Assessment of Cancer Therapy-Anemia (FACT-An [anemia sub-scale]) and Cancer Linear Analogue Scale (CLAS) at study entry, after two chemotherapy cycles, and at study end.. Mean baseline Hb was 10.43 g/dL. Hb increases (g/dL) from baseline after 4, 8, 12 weeks and at study end were 1.07, 1.77, 1.92 and 1.71 g/dL, respectively. Response rates (Hb increase > or =1 and > or =2 g/dL during trial) were 81% and 61%, respectively. Mean increases in the FACT-An score from baseline (mean 55.4) were 3.1 after two chemotherapy cycles and 3.3 at study end; mean increases in the CLAS score from baseline (58.4 mm) were 5.9 mm after two chemotherapy cycles and 6.5 mm at study end.. The greatest QoL increase was recorded when patients approached Hb level of 12 g/dL, independent of the baseline Hb level. Hb changes from baseline to trial end were related to corresponding changes in the FACT-An score. A positive correlation was also observed in patients with progressive disease. Adverse events were essentially those associated with chemotherapy. Incidence of thrombovascular events (6.7%) did not differ from the expected standard treatment in cancer patients. Epoetin alfa 40,000 IU qw increased Hb levels and improved or preserved QoL.

Topics: Aged; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins

Chemotherapy-induced anemia (CIA) may substantially impact the health-related quality of life (HRQoL) of older cancer patients. This exploratory analysis evaluated the effect of darbepoetin alfa administered as a fixed dose (300 microg) every 3 weeks (Q3W) on hematologic outcomes, HRQoL, and safety in older (> or =65 years old) versus younger (<65 years old) patients with CIA (hemoglobin <11 g/dl). Patients were categorized by age at screening: <65, > or =65 to <70, > or =70 to <75, > or =75 to <80, and > or =80 years old. Patients who received at least one dose of darbepoetin alfa were included in the analysis; of 1,493 patients, 724 were > or =65 years old. Age did not appear to influence hematologic outcomes after treatment with darbepoetin alfa; in all age categories, similar percentages of patients (78%-80%) achieved the target hemoglobin in approximately the same time (4-5 weeks). Also, the percentage of patients in each age category who received RBC transfusions was reduced from 10%-13% in month 1 to 2%-4% in month 4. Although younger patients reported the greatest improvement in HRQoL scores, approximately one half in each older age category reported clinically significant improvement in fatigue, and improvement in the Energy and Overall Health Assessment and Work Productivity and Activity Impairment scales. There were no treatment-related deaths. Treatment-related thromboembolic events were reported by <1% of patients <65 years old and <1% of patients > or =65 to <70 and > or =70 to <75 years old. Darbepoetin alfa Q3W appeared well tolerated and effective for treating older patients with CIA.

Topics: Activities of Daily Living; Adult; Age Factors; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Biomarkers; Darbepoetin alfa; Drug Administration Schedule; Erythrocyte Transfusion; Erythropoietin; Fatigue; Female; Follow-Up Studies; Hematinics; Hemoglobins; Humans; Karnofsky Performance Status; Male; Middle Aged; Neoplasms; Quality of Life; Research Design; Surveys and Questionnaires; Treatment Outcome

The purpose of this study was to evaluate the safety and efficacy of epoetin alfa (EPO) at an initial dose of 60,000 Units (U) once weekly (QW) followed by extended dosing of 80,000 U every 3 weeks (Q3W) in patients with chemotherapy-induced anemia (CIA).. Anemic patients (hemoglobin [Hb] < or = 11 g/dl) receiving Q3W chemotherapy for nonmyeloid malignancy were enrolled in this prospective, open-label, single-arm study to receive EPO 60,000 U subcutaneously (SC) QW (initial dosing phase [IDP]) until a target Hb level of 12 g/dl was reached (maximum 12 weeks). Patients who achieved an Hb level of 12 g/dl at any point during the IDP then entered the extended dosing phase (EDP; EPO 80,000 U SC Q3W). Maximum study duration (IDP + EDP) was 24 weeks. The primary endpoint was the proportion of patients achieving a hematopoietic response (Hb increase > or = 2 g/dl from baseline or Hb > or = 12 g/dl) during the IDP.. One hundred fifteen patients were enrolled. During the IDP, 76% (84/110) of patients achieved a hematopoietic response, and 15% (17/115) received red blood cell (RBC) transfusion. Sixty-three percent (73/115) of patients entered the EDP, and 88% (64/73) of these patients maintained a mean Hb level > 11.0 and < or =13.0 g/dl. Two of 73 patients received RBC transfusion during the EDP. Adverse events were consistent with the underlying disease and chemotherapy treatment.. These results suggest that initiation of EPO 60,000 U SC QW is effective in the treatment of CIA and that EPO 80,000 U SC Q3W can be an effective extended dosing option.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Recombinant Proteins; Treatment Outcome

To evaluate if a darbepoetin alfa correction/maintenance dosing regimen is non-inferior to a weekly regimen with respect to red blood cell transfusion requirements in patients with chemotherapy-induced anemia (CIA).. In this randomized, active-controlled, double-blind phase 3 trial, CIA patients were randomized 1:1 to receive darbepoetin alfa in either a correction/maintenance schedule (4.5 microg/kg weekly for 4 weeks followed by 4.5 microg/kg every 3 weeks (Q3W)) or a weekly schedule (2.25 microg/kg weekly). The primary endpoint was the transfusion incidence during weeks 1-16. Non-inferiority was to be concluded if the upper limit of the 95% confidence interval (CI) of the difference in transfusion incidence between treatment groups was below 12.5%. Hematologic responses and safety profiles were also compared.. Transfusion incidence (95% CI) during weeks 1-16 was 37% (32-42) and 38% (32-43) in the weekly and correction/maintenance groups, respectively. The difference (95% CI) in transfusions was 0.4% (-7.0 to 7.8), demonstrating non-inferiority between treatment groups. Similar percentages in both groups achieved and maintained hemoglobin in a target range of 11-13 g/dL and had clinically meaningful FACT-F score improvements. The median (range) time to hemoglobin response was 10 (1-17) weeks and 12 (2-17) weeks in the weekly and correction/maintenance groups, respectively. Both groups had similar safety profiles.. A correction/maintenance schedule with its initial two-fold higher weekly dosing and subsequent Q3W dosing yielded outcomes similar to those observed with a weekly schedule. Although correction/maintenance dosing provided no incremental clinical benefit, Q3W dosing could provide benefits of convenience and facilitate patient compliance.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Anemia; Antineoplastic Combined Chemotherapy Protocols; Darbepoetin alfa; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Routes; Drug Administration Schedule; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Polypharmacy; Treatment Outcome

This randomized, controlled trial evaluated the effect of darbepoetin alfa on hospitalization days, transfusion requirements, hemoglobin levels, and fatigue in patients with anemia of cancer (AOC). Eligible patients were anemic (hemoglobin or=18 years old, and had not received chemotherapy or radiotherapy within 4 weeks of study screening. Patients were randomized 4:1 to receive darbepoetin alfa, 3.0 microg/kg every 2 weeks (Q2W) (n = 226), or observation only for 12 weeks (n = 59), followed by an optional 9 weeks of darbepoetin alfa, 3.0 microg/kg Q2W. Endpoints were compared between the two treatment arms at week 13. A planned interim analysis indicated that assumptions regarding hospitalization in the study design were incorrect, so the study was terminated early. Therefore, results for the primary endpoint should be interpreted cautiously. The hospitalization rate was similar (0.5 days) for both the darbepoetin alfa and observation groups (p = .73). Transfusion incidence (weeks 5-12) was significantly lower for darbepoetin alfa patients (8%) than for observation patients (22%) (p = .0092). By week 13, hemoglobin increased by 2.1 g/dl in patients receiving darbepoetin alfa, compared with 0.1 g/dl in the observation group p < .0001. Hemoglobin improvements were paralleled by an increase in Functional Assessment of Cancer Therapy-Fatigue score (mean change in score at week 13: darbepoetin alfa, 6.0; observation, 2.2; p < .05). Darbepoetin alfa Q2W can significantly improve hemoglobin levels and reduce transfusion requirements in patients with AOC, resulting in significant improvements in health-related quality of life.

Topics: Aged; Aged, 80 and over; Anemia; Darbepoetin alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Pulmonary Embolism; Treatment Outcome; Venous Thrombosis

Treatment with erythropoiesis-stimulating factors (ESFs) can ameliorate anemia associated with cancer and chemotherapy. However, half of anemic cancer patients do not respond even to high doses. To determine factors that are predictive of a treatment response, a multicenter, prospective study was performed.. Investigated factors were baseline erythropoietin, reticulocytes and soluble transferrin receptor (sTfR) after 2 weeks, and reticulocytes and hemoglobin after 4 weeks. Anemic patients with solid tumors received 150 microg/week of darbepoetin concomitantly with chemotherapy. The dose was doubled if hemoglobin did not increase by >1 g/dl after 4 weeks. Patients were considered responders if hemoglobin increased by >or=2 g/dl or reached a level >or=12 g/dl within 8-12 weeks.. In total, 196 patients were enrolled; 61% of the intention-to-treat (ITT) and 68% of the per-protocol population were responders. In the ITT population, the hemoglobin increase after 4 weeks indicated an 11-fold higher chance of response (odds ratio, 11.0; 95% confidence interval [CI], 5.1-23.6; sensitivity, 88%; specificity, 60%). In a multiple logistic regression model including all factors, the area under the receiver operating characteristic curve was 0.78 (95% CI, 0.71-0.84). The combination of sTfR after 2 weeks and hemoglobin after 4 weeks was as predictive as the combination of all five tested factors.. So far, an early hemoglobin increase remains the single most predictive factor for response to ESF treatment. In contrast to anemic patients with lymphoproliferative malignancies, serum erythropoietin had little predictive value in patients with solid tumors.

Topics: Aged; Anemia; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Prognosis; Prospective Studies; Recombinant Proteins; ROC Curve; Treatment Outcome

Anemia is a common problem in the cancer population that is the result of clinical consequences. It also has adverse effects on patients' perceived quality of life. Good management of anemia in the cancer population is therefore essential. A recent published clinical trial has demonstrated statistically significant increases in hemoglobin levels and significantly increased QOL assessment following the administration of recombinant erythropoietin.. To evaluate the effectiveness, the safety, and the quality of life by using once weekly dosing of Epoetin alfa (Eprex, Janssen-cilag) 40,000 units in the treatment of anemia in cancer patients receiving chemotherapy.. Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University Bangkok, Thailand.. This was an open label, non-randomized study, in 41 adult male and female anemic cancer patients who had non-myeloid malignancies in the upper area of the body part and hemoglobin ranging from 9-11 g/dL receiving chemotherapy at least 8 weeks with or without concurrent radiotherapy. The subjects were treated with Epoetin alfa 40,000 units once a week subcutaneously. If, the hemoglobin did not increase by > 1.0 g/dl after 4 weeks of treatment, the dose of Epoetin alfa was then increased to 60,000 units per dose subcutaneously at week 5. The Epoetin alfa treatment would continue for a total of 16 weeks. Clinical outcome was evaluated based on quality of life by using the linear analog scale assessment (LASA) and the functional assessment of cancer therapy-anemia (CU-QOL) instrument. Analyses were performed to determine the incremental change in QOL associated with hemoglobin increases.. Seventy six percent of patients receiving Epoetin alfa subcutaneously showed good response with hemoglobin increases of > or = 1 g/dL (Hb level before and after = 9.82 +/- 0.78 g/dL and 12.56 +/- 1.49 g/dL, respectively; p < 0. 001). Improvement of all primary cancer- and anemia-specific QOL domains, including energy level and ability to do daily activities evaluated from LASA and fatigue assessed from CU-QOL, were significantly greater (p < 0.01) for week 16 (233.94 +/- 56.01 and 18.45 +/- 13.07) compared to the baseline (202.58 +/- 36.74 and 25.09 +/- 11.00). Epoetin alfa was well tolerated in all patients.. Once weekly dosing of Epoetin alfa 40,000 units therapy is safe and effective in remodeling anemia and significantly improves the quality of life in cancer patients receiving chemotherapy. Therefore, the physician should maintain hemoglobin concentration of cancer patients in normal level to improve their quality of life through the chemotherapy period.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins; Surveys and Questionnaires; Treatment Outcome

The optimal hemoglobin concentration at which to initiate erythropoietic therapy for chemotherapy-induced anemia (CIA) is not well defined. This randomized, open-label, multicenter study evaluated the ability of darbepoetin alfa (300 microg every 3 weeks) to maintain hemoglobin levels > or =10 g/dl in patients with CIA (hemoglobin > or =10.5 g/dl and < or =12.0 g/dl) randomized 1:1 to an immediate-intervention group (received darbepoetin alfa immediately) or observation group (received darbepoetin alfa if hemoglobin fell to <10 g/dl). In 201 evaluable patients, there was a significant difference between the two groups in the Kaplan-Meier proportion of patients with a hemoglobin decrease to <10 g/dl during weeks 1-13 (test period) (primary endpoint): 29% for immediate-intervention patients versus 65% for observation patients. Sixty-four patients in the observation group received darbepoetin alfa (delayed-intervention subgroup). The Kaplan-Meier proportion of patients who received transfusions was lower in the immediate-intervention group than in the delayed-intervention subgroup (14% versus 31% for the test period; 17% versus 36% over the whole study). The target hemoglobin level (> or =11 g/dl) was achieved by a higher percentage of patients (crude percentage) in less time in the immediate-intervention group (94% in 2 weeks) than in the delayed-intervention subgroup (73% in 6 weeks); hemoglobin endpoints for the delayed-intervention subgroup were calculated from recalibrated study week 1 (the date patients first received darbepoetin alfa). For both groups, a higher mean change in hemoglobin from baseline led to a greater improvement in Functional Assessment of Cancer Therapy-Fatigue scores. In conclusion, immediate intervention resulted in a significantly lower proportion of patients who experienced a decline in hemoglobin, lower requirement for transfusions, and greater proportion of patients achieving and maintaining the target hemoglobin level.

Topics: Aged; Anemia; Antineoplastic Agents; Darbepoetin alfa; Dose-Response Relationship, Drug; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Time Factors; Treatment Outcome

The primary aim of the present study was to examine the relationship of changes in hemoglobin levels following recombinant human erythropoietin (rHuEPO) treatment to changes in cognitive functioning studied by Mini Mental State Examination (MMSE) in elderly cancer patients undergoing chemotherapy treatment. The secondary aim was that to assess the relationship of changes in hemoglobin levels following rHuEPO treatment to changes in functions studied by Comprehensive Geriatic Assessment (CGA), such as Activity of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Geriatric Depression Scale (GDS) and the Mini Nutritional Assessment (MNA). To this end, hemoglobin levels and cognitive functioning were evaluated in a sample of cancer patients prior to the start of chemotherapy treatment and again after 4, 8 and 12 weeks of treatment with chemotherapy plus rHuEPO. Ten elderly patients (mean age 71.4 years) were enrolled. At baseline, enrolled patients had a mean Hb value of 10.3g/dl. After 4 weeks of rHuEPO treatment, Hb values increased significantly (p<0.0001), with a mean increase of 1.2g/dl (range: 0.2-2.1). Remarkably, 8 out of 10 (80%) showed an increase of Hb levels >or=1g/dl in comparison to baseline and therefore were considered responders. At baseline, four patients (40%) showed a moderate cognitive impairment, whilst six patients (60%) showed a normal cognitive function. After 4 weeks of rHuEPO treatment nine patients (90%) showed a significant improvement of cognitive functions in comparison to baseline (p<0.005): eight of them were responders also to rHuEPO in terms of correction of anemia. The Spearman's rank correlation test showed a statistical significant correlation between Hb increase and increase in cognitive functioning assessed by MMSE after 4 weeks (p=0.049), 8 weeks (p=0.044) and 12 weeks (p=0.031) of rHuEPO treatment. Therefore, the findings of this study provide support for the hypothesis that significant increases in hemoglobin over the course of chemotherapy supplemented with rHuEPO administration would be accompanied by significant improvement in cognitive performance over the same interval.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Cognition; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Female; Geriatric Assessment; Hemoglobins; Humans; Male; Neoplasms; Recombinant Proteins

To evaluate the effect of epoetin alfa on quality of life (QOL) in patients with solid tumors and mild-to-moderate anemia receiving platinum-based chemotherapy relative to population norms.. In the original study, patients (n = 316) with hemoglobin (Hb) levels < or =12.1 g/dl were randomized 2:1 to receive either epoetin alfa at a dose of 10,000 U thrice weekly s.c. or best supportive care (BSC) to compare the effects on transfusion use, hematologic response, and QOL (measured by the Functional Assessment of Cancer Therapy-Anemia [FACT-An]and Cancer Linear Analogue Scale [CLAS]). The QOL data from this previously reported trial were reanalyzed here relative to population norms.. Mean baseline QOL scores were similar between groups. At study completion, mean CLAS, FACT-An, FACT-An Anemia subscale, and FACT-An Fatigue subscale scores were significantly higher for patients given epoetin alfa than for those treated with BSC. Compared with population norms, both groups had impaired QOL at baseline. Differences in mean QOL change scores from baseline to study end for epoetin alfa versus BSC were 3.17 points for the FACT-General Total, 9.90 for the FACT-An Fatigue subscale, and 7.30 for the FACT-An Anemia subscale. This was equivalent to corrections in QOL deficits attributable to epoetin alfa of 97.3%, 40.7%, and 38.0% for the FACT-General Total, FACT-An Fatigue, and FACT-An Anemia subscale scores, respectively, versus BSC. A somewhat greater QOL benefit was observed for the FACT-An Fatigue and FACT-An Anemia subscales in the subset of patients with baseline Hb levels >10.5 g/dl.. Patients in this study had impaired QOL compared with population norms. Early treatment with epoetin alfa to correct anemia improved QOL in a statistically significant and clinically meaningful way, and improvements were greater in patients with baseline Hb levels >10.5 g/dl.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Platinum Compounds; Quality of Life; Recombinant Proteins; Reference Values; Sickness Impact Profile; Treatment Outcome

This analysis of the results of a randomized, controlled trial evaluating the effects of epoetin alfa (EPO) therapy on transfusion requirements, hemoglobin (Hb), and quality of life (QOL) in patients with cancer receiving platinum-based chemotherapy was conducted to evaluate the effect of initial Hb level on study outcomes.. Patients with Hb levels < or =12.1 g/dl were randomized 2:1 to receive EPO, 10,000 U three times weekly s.c. or best supportive care (BSC) until 4 weeks after their last chemotherapy cycle. For this analysis, patients were stratified by baseline Hb level (< or =9.7 g/dl, >9.7 g/dl to < or =10.5 g/dl, >10.5 g/dl to < or =11.3 g/dl, and >11.3 g/dl to < or =12.1 g/dl), and study results were reanalyzed.. Significantly fewer EPO patients than BSC patients with initial Hb levels >9.7 g/dl to < or =12.1 g/dl required transfusions. EPO maintained Hb levels throughout the study for patients with Hb levels >11.3 g/dl to < or =12.1 g/dl, compared with a decrease with BSC. For patients with baseline Hb levels >10.5 g/dl, for whom the mean changes from baseline to last assessment were measured by the Cancer Linear Analogue Scale assessments of energy and overall QOL as well as by the Functional Assessment of Cancer Therapy (FACT)-Fatigue and FACT-An Anemia subscale, QOL scores were significantly greater with EPO than with BSC. QOL declined in patients receiving BSC, and the mean decreases in QOL scores were greater for BSC patients with baseline Hb levels >10.5 g/dl, compared with the overall BSC group.. In patients with cancer receiving platinum-based chemotherapy and with baseline Hb levels >10.5 g/dl, early intervention with EPO reduces transfusions, maintains Hb level, and maintains or improves QOL. This study supports the positive effects of early intervention when analyzed according to initial Hb value.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Blood Transfusion; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Platinum Compounds; Quality of Life; Recombinant Proteins; Sickness Impact Profile; Treatment Outcome

The pharmacokinetics of darbepoetin alfa after intravenous (IV) administration in the oncology setting have not been previously reported. The objective of this study was to evaluate the pharmacokinetics of IV or subcutaneous (SC) darbepoetin alfa in patients with non-myeloid malignancies undergoing multicycle chemotherapy.. Fifty-six patients (haemoglobin

Topics: Absorption; Adult; Aged; Area Under Curve; Darbepoetin alfa; Erythropoietin; Female; Half-Life; Humans; Injections, Intravenous; Injections, Subcutaneous; Male; Metabolic Clearance Rate; Middle Aged; Neoplasms; Tissue Distribution

Epoetin alfa is an established treatment of anemia in patients with cancer who are receiving chemotherapy with or without radiation therapy. However, fewer data support its use in patients with cancer not currently receiving either therapy. This 16-week, open-label, nonrandomized, multicenter pilot study evaluated the clinical profile of epoetin alfa (40,000 U) administered weekly via subcutaneous injection in anemic patients with cancer not receiving chemotherapy or radiation therapy. The primary endpoint was the proportion of patients who achieved a minor (hemoglobin [Hgb] increase > or = 1-1.9 g/dL) or major (Hgb increase > or = 2 g/dL) hematologic response. The trial was temporarily suspended to amend the protocol to reflect updated package insert recommendations for target Hgb and dose adjustments. Of the 98 patients enrolled, 91 (mean age, 69.5 +/- 9.5 years; baseline Hgb level, 10.4 +/- 0.7 g/dL) were evaluated for efficacy in a modified intent-to-treat analysis. Nearly all patients (94.5% [86/91]) achieved a minor response, and the majority (80.2% [73/91]) achieved a major hematologic response at any time during the study. Mean Hgb levels increased steadily over the 12-week dosing period, with significant (P < 0.001) increases from baseline observed as early as week 2. Only one patient required a transfusion. Epoetin alfa was safe and well tolerated.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Pilot Projects; Recombinant Proteins

Chemotherapy-induced anemia is widely treated in the United States with darbepoetin alfa (DA) or epoetin alfa (EA). This noninferiority study systematically compares efficacy and safety of DA and EA using common doses and schedules used in clinical practice.. Patients had a diagnosis of nonmyeloid malignancy with > or = 8 weeks of planned chemotherapy, age >or = 18 years, and anemia (hemoglobin < or = 11 g/dL). Patients were randomly assigned 1:1 to DA 200 microg every two weeks (Q2W) or EA 40,000 units every week (QW) for up to 16 weeks with identical dose adjustment rules. Efficacy was assessed by the incidence of RBC transfusion (Kaplan-Meier estimate). The definition of noninferiority was that the upper 95% CI limit of the observed difference in RBC transfusions between groups was less than 11.5%; this noninferiority margin was based on the treatment effect observed in placebo-controlled EA studies.. Of 1,220 patients randomly assigned, 1,209 received > or = one dose of the study drug. Common tumor types were lung (26%), breast (21%), and gastrointestinal (18%). Transfusion incidence from week 5 to the end of the treatment phase (the primary end point) was 21% in the DA group and 16% in the EA group; noninferiority was concluded because the upper 95% CI limit of the difference between groups (10.8%) was below the prespecified noninferiority margin. Sensitivity analyses using alternate statistical methods and analysis sets yielded similar results. Hemoglobin, quality of life, and safety end points further support equivalency of the erythropoietic therapies.. This large, phase III study demonstrates comparable efficacy of DA Q2W and EA QW. Less frequent dosing offers potential benefits for patients, caregivers and health care providers.

Topics: Aged; Anemia; Antineoplastic Agents; Blood Transfusion; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Treatment Outcome

This randomized, open-label, multicenter study compared the efficacy and safety of epoetin alfa (EPO) 80 000 U every 2 weeks (Q2W) to the FDA-approved regimen of 40 000 U weekly (QW) in patients with chemotherapy-induced anemia.. A total of 310 patients with nonmyeloid malignancy and baseline hemoglobin (Hb)

Topics: Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Recombinant Proteins

To evaluate the effects of once-weekly epoetin alfa (EPO) on health-related quality of life (HRQOL), hemoglobin (Hb), transfusions, and tolerability in children with cancer.. Anemic patients 5 years to 18 years of age receiving myelosuppressive chemotherapy for nonmyeloid malignancies, excluding brain tumors, received intravenous EPO 600 units/kg to 900 units/kg or placebo once-weekly for 16 weeks. Patients and parents completed the pediatric health-related quality-of-life generic scales (GS) and cancer-specific scales (CS).. One hundred eleven patients received EPO and 111 patients received placebo. Mean final values for GS total score (P = .763 among patients; P = .219 among parents) and CS domain scores (P > or = .238; P > or = .081, respectively) were not significantly different between treatment groups. EPO-treated patients had greater increases in Hb overall (P = .002) and were more likely to be transfusion free after 4 weeks (38.7% v 22.5%; P = .010). Change in Hb was correlated with change in PedsQL-GCS total score in the EPO group (r = 0.242; P = .018), but was not in the placebo group (r = 0.086; P = .430). Adverse events were comparable between treatment groups.. This study confirmed the tolerability and hematologic benefits of once-weekly EPO in children with cancer. No significant difference in HRQOL was detected between treatment groups, but a significant positive correlation was observed between Hb changes and HRQOL changes in the EPO group. Additional studies are warranted to assess HRQOL when anemia is managed optimally in children with cancer.

Topics: Adolescent; Anemia, Hypochromic; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Child; Child, Preschool; Double-Blind Method; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Health Status; Hematinics; Hemoglobins; Humans; Male; Neoplasms; Quality of Life; Recombinant Proteins

This pilot study was conducted to evaluate the feasibility, activity, and safety of an induction dose of epoetin alpha in cancer patients with moderate or severe anemia who were receiving chemotherapy.. Thirty patients with solid tumors and hemoglobin (Hb) levels <11.0 g/dl were enrolled. Patients received single s.c. injections of epoetin alpha, 40 000 IU for three consecutive days, and were then observed for the following 30 days. The primary efficacy variable was the response rate (Hb increase > or=1 g/dl) at day 15. Secondary efficacy variables included the proportion of patients given blood transfusions between baseline and the end of study, the duration of response (Hb level > or=1 g/dl), and ability to maintain the planned chemotherapy dose (dose intensity).. At day 15, 23 of 30 (77%) patients had achieved increases in Hb levels of at least 1 g/dl. The mean Hb increase in responders was 2.0 g/dl [95% confidence interval (CI) = 1.7-2.3 g/dl]. The Hb increase was 2.3 +/- 0.7 g/dl in responders with baseline Hb levels <9.5 g/dl (median Hb value), and 1.7 +/- 0.6 g/dl in those with higher Hb levels (P = 0.012). The median duration of response was 6.1 weeks (95% CI = 1.6-10.6 weeks). Hematologic parameters were not significantly changed in nonresponders. Multivariate analysis detected no significant differences in Hb increase at day 15 on the basis of age, sex, weight, baseline Hb levels, type or stage of tumor, or treatment with platinum-based chemotherapy. No serious adverse event related to epoetin alpha treatment was observed.. We conclude that a higher initial dosing of epoetin alpha appears to be an efficient schedule for treating anemia in cancer patients undergoing chemotherapy, conferring higher response rates than those seen with standard doses. Further evaluation of these and other epoetin alpha dosage regimens is warranted.

Topics: Adult; Aged; Anemia; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematopoiesis; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins

Anemia is frequently observed in patients undergoing chemotherapy. Administration of darbepoetin alfa, a recombinant erythropoiesis-stimulating agent that has longer residence time than endogenous erythropoietin, to patients with chemotherapy-induced anemia (CIA) increases mean hemoglobin concentration, reduces risk of red blood cell transfusions, and improves patient-reported outcomes. A pharmacokinetic/pharmacodynamic (PkPd) model was developed using data from patients with nonmyeloid malignancies and CIA who were receiving darbepoetin alfa. A 2-compartment Pk model with linear elimination described the Pk data obtained in 140 CIA patients after intravenous and subcutaneous (s.c.) doses of 2.25 microg/kg every week and s.c. doses of 6.75 microg/kg every 3 weeks. The population typical values of key Pk parameters were clearance, 2010 mL/day; steady-state volume of distribution, 3390 mL; and bioavailability, 44.3%. A modified indirect response model, wherein serum concentrations stimulated the production of hemoglobin through an Emax-type equation, described the hemoglobin levels after s.c. doses of 0.5 microg/kg every week to 15 microg/kg every 3 weeks in 573 CIA patients. The estimated incremental maximum stimulation of hemoglobin production was 43.7% and darbepoetin alfa serum concentration at half-maximal stimulation was 3.68 ng/mL. The impact of covariates (body weight and platinum-containing chemotherapy) on the PkPd response was evaluated based on point and interval estimates of parameters, rather than through stepwise hypothesis testing. The final PkPd model adequately predicted hemoglobin response in a test data set, thereby confirming the predictive capability of the model. Based on simulations, it was not possible to categorize the influence of any covariate as clinically important.

Topics: Anemia; Darbepoetin alfa; Drug Therapy; Erythropoietin; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Models, Biological; Neoplasms; Population

To determine whether weekly epoetin alfa could improve hemoglobin (HgB) levels, reduce RBC transfusions, and improve quality of life (QOL) in patients with advanced cancer and with anemia after receiving myelosuppressive chemotherapy.. This double-blind, placebo-controlled study randomly assigned patients to placebo or epoetin alfa (Ortho Biotech, Bridgewater, NJ) 40,000 U subcutaneous weekly for 16 weeks. QOL, HgB, and RBC transfusions were measured pretreatment and monthly.. The study accrued 344 patients; 330 were assessable for efficacy and 305 were assessable for QOL. Placebo-treated patients had a mean increase in HgB of 0.9 g/dL (range, -3.8 to +5.3) compared with 2.8 g/dL (range, -2.2 to +7.5) for epoetin-treated patients (P < .0001). During the study, 31.7% of placebo-treated patients achieved a > or = 2 g/dL HgB increase compared with 72.7% of epoetin-treated patients (P < .0001). The incidence of RBC transfusion for placebo and epoetin treatment arms was 39.6% and 25.3% (P = .005), respectively. The placebo group received 256 units of RBCs compared with 127 units in the epoetin group (P < .0001). The incidence of toxicity in the groups was similar. Changes in the average QOL scores from baseline to the end of the study were similar in the two groups (P = not significant). The HgB responders (irrespective of treatment arm) had a mean change in Functional Assessment of Cancer Therapy (FACT) fatigue score from a baseline of +5.1 compared with -2.1 for the nonresponders (P = .006).. Epoetin alfa significantly improved HgB and reduced transfusions in this patient population. These results support the use of weekly epoetin alfa as an ameliorative agent for cancer-related anemia.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Breast Neoplasms; Double-Blind Method; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Injections, Subcutaneous; Lung Neoplasms; Male; Middle Aged; Neoplasms; Placebos; Quality of Life; Recombinant Proteins; Treatment Outcome

The patterns of use and effectiveness of therapy with darbepoetin alfa and epoetin alfa for chemotherapy-induced anemia (CIA) in hospital outpatient and community settings were evaluated.. Data were collected from medical charts at 65 oncology clinics in hospital outpatient and community settings for consecutive patients who received the first dose of either darbepoetin alfa or epoetin alfa between August 1, 2002, and February 15, 2003, and were to have had 12 weeks of follow-up data.. Data from the charts of 3123 patients were abstracted. Of these patients, 2785 were treated with only one erythropoietic agent (1444 with darbepoetin alfa and 1341 with epoetin alfa) and were included in the analysis. The most common initial dosage of darbepoetin alfa was 200 microg every two weeks (61% of darbepoetin alfa recipients), and the most common initial dosage of epoetin alfa was 40,000 units weekly (72%). With these regimens, the dosage was escalated for 22% of darbepoetin alfa recipients and 23% of epoetin alfa recipients at a median of six weeks after the initial dose. The mean change from baseline in hemoglobin concentration after 12 weeks of therapy was similar for both groups, as was the percent of patients with red-blood-cell transfusions during treatment.. The most common initial dosage of darbepoetin alfa for CIA was 200 microg every two weeks, and the most common initial dosage of epoetin alfa was 40,000 units weekly. At these dosages, the two agents appear to have similar clinical effectiveness.

Topics: Aged; Anemia; Antineoplastic Agents; Cohort Studies; Darbepoetin alfa; Data Collection; Drug Administration Schedule; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hemoglobins; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Outpatients; Recombinant Proteins; Retrospective Studies; Time Factors; Treatment Outcome

This prospective, open-label, multicenter study was undertaken to determine the safety and efficacy of epoetin alfa in increasing hemoglobin levels and improving quality of life (QOL), specifically fatigue, in cancer patients receiving chemotherapy with or without radiotherapy (n=702). Epoetin alfa, 10,000 IU three times a week s.c. for 8-18 weeks, increased the mean hemoglobin level relative to baseline (1.0 +/- 1.5 g/dl by week 4 and > or =1.7 g/dl from week 10 through the end of the trial), with 63.4% of patients experiencing > or =2 g/dl increases in hemoglobin above baseline at some time during the study. Fatigue is an important component of QOL. Physicians, nurses, and patients independently assessed patient fatigue level on a linear-analogue scale. Although all three groups reported improvements in patient fatigue over the course of the study (p <.0001), the magnitude of fatigue ratings and their relationship to tumor response and to hemoglobin level varied by group. Overall, epoetin alfa was well tolerated and effective in improving hemoglobin levels and decreasing fatigue in patients undergoing chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins; Treatment Outcome

We performed a phase I study of two fixed dosing schemes of cisplatin, a DNA cross-linker, with intravenous escalating topotecan, a DNA-topoisomerase I inhibitor.. 40 patients with advanced solid tumors received intravenous cisplatin at a fixed dose of either 25 mg/m2 (schedule A) or 20 mg/m2 (schedule B) daily for 3 days with standard hydration. Topotecan escalation proceeded in 0.75, 0.90, 1.0, 1.15 mg/m2 cohorts in schedule A and 1.0, 1.1, 1.2, 1.3 mg/m2 cohorts in schedule B, administered intravenously at the end of cisplatin infusion daily for 3 days, repeated every 3 weeks. Dose-limiting toxicity (DLT) consisted of protracted grade IV neutropenia, febrile neutropenia, grade IV thrombocytopenia and any grade III/IV non-hematological toxicity. Epoetin and granulocyte colony-stimulating factor support was allowed on severe myeloablation. Endpoints were the identification of maximal tolerated dose (MTD), DLT and other toxicity.. The MTD was reached in cohort 25/1.15 mg/m2 in schedule A and 20/1.2 mg/m2 in schedule B. All DLT seen consisted of three episodes of febrile neutropenia and two of grade IV thrombocytopenia in schedule A, with three episodes of febrile neutropenia and one of protracted neutropenia in schedule B. Myelosuppression was substantial in all cohorts despite granulocyte colony-stimulating factor and epoetin support, peaked on the third week of treatment and resulted in administration of chemotherapy at a median of every 4 weeks. Non-hematologic toxicity was mild. The response rate was 51% with seven complete responses occurring in patients with ovarian cancer, small cell and non-small cell lung cancer and cancer of unknown primary. The recommended dose was 20/ 1.1 mg/m2 for cisplatin and topotecan on schedule B, as the number of responses and administered topotecan dose were higher in schedule B recommended dose with lower cisplatin dose, minimizing problems of nephrotoxicity and vomiting.. The schedule B daily cisplatin-topotecan x 3 combination with secondary cytokine support is associated with promising activity and schedule convenience. However, substantial myelosuppression undermines its applicability in the palliative setting, stressing the need for less toxic regimens.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Hematinics; Humans; Infusions, Intravenous; Male; Maximum Tolerated Dose; Middle Aged; Neoplasms; Neutropenia; Recombinant Proteins; Topotecan

Cancer-related anaemia is associated with fatigue that adversely affects patients' everyday functioning and wellbeing. We explore the impact of fatigue on patient productivity and caregiver burden.. The analyses are based on data from a randomised, open-label, active-controlled, dose-finding trial of darbepoetin alfa among solid-tumour cancer patients with anaemia, who are receiving chemotherapy. Fatigue is assessed with the Functional Assessment of Cancer Therapy (FACT)-Fatigue subscale score. Productivity and caregiver outcomes include time (hours) missed from usual activities, amount of assistance (hours) needed from others, overall ability to perform desired activities and ability to perform family responsibilities. These outcomes are assessed at baseline and the end of the 12-week treatment period. ANOVA and linear regression models are used to evaluate associations.. Patients (n=300) were aged 61 years on average, with a mean (SD) baseline haemoglobin of 9.9 (0.9) g/dL. FACT-Fatigue subscale score improvements were significantly (p=0.003) associated with haemoglobin improvements. Over a 2-week period, after controlling for age, sex and disease progression, one-point improvements in FACT-Fatigue subscale scores corresponded to a 1-hour (95% CI 0.5, 1.5) gain in productive time, 0.7-hour (95% CI 0.4, 1.0) reduction in caregiver time and 1.6% (95% CI 1.4, 1.7) improvement in overall activity.. Reducing fatigue is associated with gains in productive time, reductions in caregiver burden and enhanced ability to perform activities. These outcomes may have broader implications for patients' wellbeing and for the societal impact of cancer-related fatigue and anaemia.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Darbepoetin alfa; Dose-Response Relationship, Drug; Efficiency; Erythropoietin; Fatigue; Female; Humans; Male; Middle Aged; Neoplasms

The introduction of longer-acting erythropoietic agents into the practice of oncology has demanded an understanding of the interaction of chemotherapy with the pharmacokinetics and haematological effects of these erythropoietins. We report results of a randomised trial comparing the haematological effects of darbepoetin alfa, 6.75 mug/kg, administered once every 3 weeks to anaemic cancer chemotherapy patients on either an asynchronous (day 15) or synchronous (day 1) schedule relative to their every-3-week chemotherapy. A total of 81 patients were randomised and received the study drug (43 asynchronous; 38 synchronous). No difference was observed between groups in the primary endpoint of mean haemoglobin change after 6 weeks of therapy (P=0.45) and change scores were similar to those observed with standard weekly darbepoetin alfa therapy. In a subset of patients evaluated with intensive pharmacokinetic sampling, an increase in endogenous erythropoietin concentration (up to 4-fold) lasting approximately 1 week following chemotherapy administration was observed in both groups. Synchronous administration of darbepoetin alfa was associated with a 1.3-fold increase in the area under the darbepoetin alfa concentration-time curve compared with asynchronous administration. Our data suggest that darbepoetin alfa is effective administered every 3 weeks regardless of timing of administration with respect to chemotherapy and that receptor-mediated uptake by the erythron may be an important clearance mechanism for erythropoietic proteins.

Topics: Adult; Aged; Antineoplastic Agents; Area Under Curve; Darbepoetin alfa; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Treatment Outcome

We evaluated Darbepoetin alpha (Aranesp; Amgen), a novel erythropoietic protein, in patients who developed anemia while receiving chemotherapy. Seventy-five patients (median age 62 years, range 40-81 years) undergoing different cancer chemotherapy regimens were treated with darbepoetin alpha. Therapy was started if hemoglobin (Hb) levels fell below 10 g/dl or if symptomatic anemia developed. Treatment effect was evaluated after 4 weeks, 8 weeks and at the end of therapy (up to 12 weeks). If no increase in Hb was seen after 4 weeks, the dose of darbepoetin alpha was increased to 300 microg. Patients were questioned about fatigue and any change during treatment, with evaluation according to a four-point scale, where 0 = no fatigue and 3 = severe fatigue. We observed a treatment response in 54 of 75 patients (72%). Dose escalation was necessary in 30 of 75 patients (40%) and blood transfusions were required in 13 of 75 patients (17.3%). Response was observed in 32 of 43 patients (74.4%) who had a baseline Hb < 10 g/dl and in 22 of 32 (68.8%) patients who had a baseline Hb > or =10 g/dl. At baseline, 60 of 75 patients (93.3%) reported fatigue of grade 2 or 3, but at the end of the 12-week follow-up period, only 26 of 68 patients (38.3%) reported fatigue at these levels. We conclude that darbepoetin alpha is a highly effective and well-tolerated drug in the treatment of chemotherapy-associated anemia. Patients benefited both in terms of Hb levels and control of chemotherapy-related symptoms.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Blood Transfusion; Darbepoetin alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Middle Aged; Neoplasms; Prospective Studies; Quality of Life

This work was conducted to evaluate the effect of early intervention with epoetin alfa (EPO) on transfusion requirements, hemoglobin level (Hb), quality of life (QOL) and to explore a possible relationship between the use of EPO and survival, in patients with solid tumors receiving platinum-based chemotherapy. Three hundred and sixteen patients with Hb12.1g/dL were randomised 2:1 to EPO 10000 IU thrice weekly subcutaneously (n = 211) or best supportive care (BSC) (n = 105). The primary end point was proportion of patients transfused while secondary end points were changes in Hb and QOL. The protocol was amended before the first patient was recruited to also prospectively collect survival data. EPO therapy significantly decreased transfusion requirements (P < 0.001) and increased Hb (P < 0.005). EPO-treated patients had significantly improved QOL compared with BSC patients (P < 0.05). Kaplan-Meier estimates showed no differences in 12-month survival (P = 0.39), despite a significantly greater number of patients with metastatic disease in the EPO group (78% vs. 61%, P = 0.001). EPO was well tolerated. This study has shown that early intervention with EPO can result in a significant reduction of transfusion requirements and increases in Hb and QOL in patients with mild anemia during platinum-based chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Platinum; Quality of Life; Recombinant Proteins; Survival Analysis

Fatigue can be a major problem for cancer patients receiving chemotherapy, and anaemia is known to be an important contributory factor. Several studies have shown that treatment with epoetin alfa raises haemoglobin levels, reduces fatigue and improves health-related quality of life (HrQoL). However, it is often difficult for clinicians to relate reported HrQoL improvements from clinical trials to meaningful benefits for their patients. Results from a large-scale, placebo-controlled study were used to determine the minimally important difference in HrQoL, defined as the 'smallest difference in score...which patients perceive as beneficial and which would mandate...a change in the patient's management'. This analysis confirmed that, for the five QoL scales used, epoetin alfa conferred not only a statistically significant but also a clinically significant benefit in terms of QoL compared to placebo, since, in each case, the benefit associated with epoetin alfa use was considerably higher than the minimally important difference.

Topics: Adult; Anemia; Antineoplastic Agents; Double-Blind Method; Epoetin Alfa; Erythropoietin; Fatigue; Female; Humans; Male; Neoplasms; Placebos; Quality of Life; Recombinant Proteins

Incomplete data are inevitable in quality-of-life (QoL) studies involving cancer patients, since a proportion of patients will not complete the trial. Traditional analyses assume that such data are missing at random, but this assumption may be incorrect. We therefore applied mixed-effects statistical models to determine the effects of non-random missing data. Models were applied to results from a large-scale, randomised study of epoetin alfa versus placebo in 375 patients receiving non-platinum-based chemotherapy. The model suggested that QoL data were not missing at random and that analyses based on an assumption of random missing data gave an over-optimistic impression of QoL changes within treatment groups. However, sensitivity analysis demonstrated that the effectiveness of treatment with epoetin alfa compared to placebo in terms of QoL benefits remained highly significant, confirming the original conclusions of the study.

Topics: Anemia; Antineoplastic Agents; Data Collection; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Neoplasms; Placebos; Quality of Life; Recombinant Proteins

Anaemia is an important factor in the fatigue experienced by many patients receiving chemotherapy. A recent large-scale, randomised, placebo-controlled trial has shown that treatment with epoetin alfa raises haemoglobin levels, reduces fatigue and improves overall quality of life (QoL). In order to examine the relationship between anaemia and QoL more closely, we performed multiple regression analyses, adjusting for possible differences in demographic and clinical characteristics between the treatment groups on the trial data derived from FACT, CLAS and SF-36 QoL assessments. This confirmed that QoL is correlated with haemoglobin levels and that treatment with epoetin alfa is associated with a significant improvement in QoL as measured by validated cancer-specific instruments such as FACT and CLAS. However, the sub-group of patients who suffer disease progression during treatment are not predicted to experience an improvement in QoL, confirming the sensitivity of these scales. Race and tumour type were significantly related to changes in QoL scores, but other factors such as age and gender did not show significant effects on QoL.

Topics: Anemia; Antineoplastic Agents; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Humans; Linear Models; Male; Middle Aged; Neoplasms; Placebos; Quality of Life; Recombinant Proteins

Anaemia is a common problem for cancer patients and often causes fatigue and reduces quality of life (QoL). Although randomised trials have repeatedly shown that treatment with epoetin alfa raises haemoglobin levels, reduces fatigue and improves overall QoL, such findings may be hard to put into a clinical context and, as a result, cancer-related fatigue remains undertreated. This study gathered data using the FACT-An QoL scale from 1400 people on an internet survey panel. The 1400 were randomly selected and chosen to be representative of the total US population. Survey results were then compared with the findings from a large placebo-controlled study involving 375 anaemic cancer patients. FACT-An showed good psychometric properties in the survey population and was able to distinguish respondents with histories of anaemia and cancer from those without. Comparing the population norm values for FACT-An with the trial data showed that treatment with epoetin alfa led to clinically meaningful improvements in cancer patients' QoL.

Topics: Anemia; Antineoplastic Agents; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Humans; Linear Models; Male; Middle Aged; Neoplasms; Placebos; Quality of Life; Recombinant Proteins; Surveys and Questionnaires

Recombinant human erythropoietin (epoetin alfa) is an effective treatment for anaemia in cancer patients, and over two-thirds of recipients experience a substantial increase in haemoglobin concentration (>2 g/dl). However, it would be helpful to identify responders before starting treatment. Some studies have suggested that high pre-treatment levels of endogenous erythropoietin pre-treatment levels of endogenous erythropoietin or other pre-treatment or early response variables are associated with a poor response to epoetin alfa, and several predictive algorithms have been published. We analysed data pooled from 9 clinical trials of 1010 patients to determine the clinical usefulness of pre-treatment erythropoietin levels and other variables for predicting response. This showed that pre-treatment factors alone do not provide a clinically useful prediction of response. The sensitivity of these models increases slightly if early response variables, such as the change in haemoglobin after 4 weeks, are included, but specificity remains poor. We conclude that, while there may be a statistical relationship between certain factors and response, none approach clinically useful levels of sensitivity or specificity.

Topics: Anemia; Antineoplastic Agents; Double-Blind Method; Epoetin Alfa; Erythropoietin; Factor Analysis, Statistical; Female; Humans; Male; Middle Aged; Neoplasms; Placebos; Recombinant Proteins

Recently the American society of clinical oncology and the American society of hematology have jointly launched the clinical practice guideline of epoetin usage in cancer related anemia patients The recommended starting dose is 150-300 unit/kg thrice weekly. The clinical outcome of epoetin alfa 10,000 units subcutaneously thrice weekly regimen has not been evaluated in Thai cancer patients with anemia yet.. To determine the clinical benefits and safety of epoetin alfa (Eprex) 10,000 units subcutaneously thrice weekly in anemic cancer patients receiving chemotherapy. The present study was an open label, non-randomized study. Adult patients were eligible for inclusion aged >18 years with a confirmed diagnosis of non-myeloid malignancy in the upper area of the body and scheduled to receive chemotherapy regardless of the concurrent radiotherapy. All patients had hemoglobin (Hb) level less than 11 g/dL, serum ferritin more than 100 ng/dL and had a life expectancy of at least 6 months.. All patients were initially treated with Epoetin alfa 10,000 units subcutaneously thrice weekly. The dose was up to 20,000 units after 4 weeks of therapy, if Hb level did not increase by > 1.0 g/dL. Treatment time was 16 weeks. Target Hb was 12 g/dL Blood transfusion and iron supplement was permitted. Efficacy Assessments: The primary efficacy end point was the proportion of responders (patients with an increase in Hb > or =1 g/dL). Secondary efficacy evaluation was change in Quality of life (QOL) scores by the Linear Analog Scale Assessment (LASA) and Quality of life-Chula (QOL-CU) scale. Statistical Analysis was t-tests, P < 0.05 was considered significant.. Forty patients (21 men and 19 women) were enrolled. Twenty five patients (62.5%) had stage of disease in grade III or IV The mean Hb levels at baseline were 8.46 +/- 1.28 g/dL. Eight patients (20%) refused to complete the course during the study. Reasons for refusing to participate included lack of time, changing the resident area or disease progression. Twenty three of 32 patients (71.8%) were responders. These patients completed the study course and showed good response. Their mean Hb levels increased gradually and reach approximately 11 g/dl by week 4 and were maintained through week 16. The significant difference in mean Hb level of baseline was initially found at week 4 of the study (10.26 +/- 1.95 g/dl; p = 0.001 vs baseline). The LASA score increased in all of three items including level of energy, ability to do daily activities, and overall QOL but not statistical significance. However, the improvement of quality of life of cancer patients, evaluated by QOL-CU, was significantly apparent after treatment, (p < 0.05). The most common adverse events were grade I flu like symptoms (17.5%) and recovered the next day.. Epoetin alfa (Eprex) 10,000 units thrice weekly significantly increased the hemoglobin levels, achieving the target hemoglobin and sustained the level in cancer patients with anemia receiving chemotherapy. Clinical benefits on functional status and quality of life were also improved. The treatment was well tolerated.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Drug Administration Schedule; Erythropoietin; Female; Hematinics; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Recombinant Proteins; Thailand; Treatment Outcome

This is the first randomized, open-label, multicenter trial designed and powered to directly compare the hemoglobin (Hb) response to epoetin alfa (EPO), 40,000 U once weekly (QW), with that to darbepoetin alfa (DARB), 200 microg every 2 weeks (Q2W), in anemic patients with cancer receiving chemotherapy (CT). Transfusion requirements, quality of life (QOL), and safety also were evaluated. Adults with solid tumors scheduled to receive CT for > or =12 weeks and with baseline Hb < or =11 g/dl were randomized to receive either EPO 40,000 U QW (n = 178) or DARB 200 microg Q2W (n = 180) s.c. for up to 16 weeks. Doses were increased for nonresponders (Hb increase <1 g/dl) after 4 (EPO) or 6 (DARB) weeks, as per National Comprehensive Cancer Network guidelines, and were reduced for a rapid rise in Hb (>1.3 g/dl [EPO] or >1.0 g/dl [DARB] within any 2-week period) or for an Hb level >13 g/dl. The proportion of patients achieving a > or =1-g/dl Hb rise by week 5, the primary end point, was significantly higher with EPO (47.0%) than with DARB (32.5%), and EPO-treated patients achieved a > or =1-g/dl Hb increase significantly earlier than those receiving DARB (median, 35 days versus 46 days). The mean increase in Hb from baseline was significantly higher at weeks 5, 9, 13, and the end of the study with EPO than with DARB. The number of units transfused per patient was significantly lower for the EPO group than for the DARB group. The proportions of patients requiring transfusions, mean QOL improvements, and tolerability profiles were similar in the two groups.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins

To examine associations between early hemoglobin response and alternative measures of efficacy following treatment with an erythropoietic agent for chemotherapy-related anemia.. Preliminary data from an ongoing randomized, multicenter, 16-week, open-label clinical trial of epoetin alfa versus darbepoetin alfa were used to dichotomize patients based on attainment of early hemoglobin response (> or = 1 g/dL increase in hemoglobin level within 4 weeks of treatment initiation). Measures of efficacy were compared between patients with early hemoglobin response and those without. Sensitivity analyses were then performed to evaluate the impact of various methods for handling censored data and hemoglobin values following blood transfusion.. Efficacy measures included: the proportion of patients with a > or = 1 g/dL increase in hemoglobin by 4 weeks or a > or = 2 g/dL increase by 8 weeks; mean hemoglobin levels at 4, 8, 12, and 16 weeks; area under the curve for change in hemoglobin level; proportion of patients who required a blood transfusion after 4 weeks; proportion of follow-up days on which patients had hemoglobin levels within the therapeutic range of 11 g/dL to 13 g/dL; and proportion of patients who never had a hemoglobin level within this range.. A total of 274 patients were included (66.1% female, mean age 62.4), of whom 48.9% had an early hemoglobin response and 51.1% did not. Mean duration of follow-up was 10.1 +/- 5.05 weeks. All metrics indicated superior longer-term response among patients with early hemoglobin response compared to patients without early response. The findings were robust across sensitivity analyses. Although the analysis establishes a significant relationship between early hemoglobin response and alternative efficacy metrics, causality cannot be inferred.. Early hemoglobin response is significantly associated with various metrics of clinical response to erythropoietic agents and is an appropriate measure for evaluating treatment effects.

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Sensitivity and Specificity; Treatment Outcome

Anaemia is present in 30%-90% of all patients with cancer, and its origin is multifactorial. Human recombinant erythropoietin has been shown to be useful in treating anemia in patients with cancer. The aim of this study was to evaluate the effectiveness of treatment of anaemia with epoetin alfa(EPO) given as a single weekly dose, and its repercussions on quality of life (QoL).. From January to October 2002, a total of 139 patients referred to our service for radiotherapy (RT) had anemia and received treatment with EPO as a single weekly dose of 40,000 IU subcutaneously, with oral iron supplement If haemoglobin (Hb) values after 1 month of treatment did not increase by > or =1 g/dl, the dose was increased to 60,000 IU/week. Treatment with EPO ended when Hb values reached > or =14 g/dl or one month after the end of RT regardless of Hb values. QoL was evaluated with the Functional Assessment of Cancer Therapy-Anaemia subscale (FACT-An) and the Cancer Linear Analogue Scale (CLAS).. Mean Hb at the start of treatment with EPO was 11.49 +/- 1.08 g/dl, and the mean value at the end of treatment was 14.52 +/- 1.41 g/dl (p < 0.001). The mean increase in Hb was 2.97 +/- 1.65 g/dl. Mean duration of treatment was 7.13 +/- 2.91 weeks. In 11 patients (7.9%) the dose was increased after 4 weeks. In 84 patients (60.4%) EPO treatment was implemented before the commencing of RT. Mean Hb values in this group was 11.34 +/- 1.11 g/dl at the start of EPO treatment, 12.69 +/- 1.56 g/dl at the start of RT, 13.96 +1.54 g/dl at the end of RT and 14.68 +/- 1.3 g/dl at the end of EPO treatment (p < 0.001). In 55 patients(39.6%) anaemia developed during RT and, therefore, EPO treatment was implemented after commencing of RT. In this group the mean Hb values were 12.29 +/- 1.6 g/dl at the start of RT, 11.72 +/- 1.01 g/dl at the start of EPO treatment, 13.97 +/- 1.53 g/dl at the end of RT and 14.28 +/- 1.54 g/dl at the end of EPO treatment (p < 0.001). Hemoglobin levels at the start of EPO were lower in patients who commenced EPO before RT (p < 0.05). In 60 patients who received combined RT and chemotherapy, mean Hb values were 11.42 +/- 1.16 g/dl at the start of EPO and 13.98 +1.55 g/dl at the end of EPO (p < 0.005). In 75 patients who had received RT alone, the mean Hb values was 11.53 +/- 1.05 g/dl at the start of EPO and 14.98 +/- 1.17 g/dl at the end of treatment (p < 0.001). Patients treated with RT alone had higher Hb levels at the end of RT and at the end of EPO treatment than did patients who had received combined treatment(p < 0.005). The duration of EPO treatment was shorter in the group treated with RT alone than in the combined treatment group (6.41 +/- 2.99 weeks versus 7.96 +/- 2.67 weeks; p < 0.005). No significant differences were observed in FACT-An and CLAS scores at the beginning and the end of the study.. Treatment with epoetin alfa as a single weekly dose significantly increased Hb levels in patients with cancer who were undergoing radiotherapy. The response was greater in patients treated with radiotherapy alone than in those receiving combined therapy. The duration of EPO treatment was shorter in the group treated with radiotherapy alone than in the combined treatment group.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Blood Transfusion; Combined Modality Therapy; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins; Treatment Outcome

This study in patients with cancer and anemia, who were receiving chemoradiation and were treated with epoetin alfa, examined the relationship between hemoglobin level and quality of life (QOL), change in hemoglobin and change in QOL, and incremental (1 g/dL) increase in hemoglobin and related incremental improvement in QOL. Data from a multicenter, open-label, prospective study of once-weekly epoetin alfa therapy in anemic cancer patients receiving chemoradiation were used to retrospectively evaluate the relationship between hemoglobin changes and QOL changes via correlation and longitudinal analyses. A sample selection correction method was used to ensure unbiased results. QOL (energy, activity, overall QOL) was measured using the Linear Analog Scale Assessment. An incremental analysis determined the greatest incremental increase in QOL associated with a 1 g/dL increase in hemoglobin level. Of the 777 patients enrolled, 464 met chemotherapy and radiotherapy eligibility criteria. Of these, 359 (77%) underwent two QOL assessments and were eligible for analysis. A nonlinear and statistically significant positive correlation was found between hemoglobin levels and Linear Analog Scale Assessment QOL scores (r = 0.32 [energy], 0.33 [activity], and 0.29 [overall QOL]; P < .0001). An incremental analysis used regression methods to characterize the changes in hemoglobin levels and QOL scores. Hemoglobin change was found to be a statistically significant determinant of QOL changes (P < .05). The greatest incremental QOL gain associated with a 1-g/dL change in hemoglobin occurred around hemoglobin 12 g/dL (range, 11-13 g/dL). A direct relationship exists between hemoglobin increases and corresponding QOL increases. Maximal incremental gain in QOL occurred when hemoglobin was approximately 12 g/dL (range, 11-13 g/dL).

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Patient Selection; Polypharmacy; Quality of Life; Recombinant Proteins

The effect of using fixed versus weight-based doses for erythropoietic agents has not been reported previously. To investigate this issue, the authors conducted a randomized Phase II study of darbepoetin alfa administered as either a fixed dose or a weight-based dose using an accelerated correction and maintenance dosing regimen (front-loading).. During the correction phase, patients with anemia (hemoglobin < 11.0 g/dL) who had nonmyeloid malignancies and who were receiving chemotherapy were given darbepoetin alfa at a fixed dose of 325 microg (n = 122) or at a weight-based dose of 4.5 microg/kg (n = 120) once weekly until they achieved a hemoglobin concentration > or = 12.0 g/dL. Patients then received darbepoetin alfa (325 microg or 4.5 microg/kg) once every 3 weeks for the remainder of the 16-week treatment period (maintenance phase).. Darbepoetin alfa resulted in high Kaplan-Meier rates of hematopoietic response (> or = 2 g/dL increase from the baseline level or a hemoglobin level > or = 12 g/dL) in both the fixed-dose group (86%; 95% confidence interval [95% CI], 78- 94%) and the weight-based dose group (84%; 95% CI, 76-92%). The median time to hematopoietic response was 34 days (95% CI, 28-44 days) for the fixed-dose group and 36 days (95% CI, 30-45 days) for the weight-based dose group. Hemoglobin concentrations were maintained at target levels for up to 16 weeks in both groups. Darbepoetin alfa was well tolerated, and no clinically significant differences between fixed doses and weight-based doses were observed.. Darbepoetin alfa was effective when administered as either a fixed dose or a weight-based dose using a front-loading approach to rapidly correct anemia and effectively maintain hemoglobin levels in patients with anemia who had malignant disease.

Topics: Aged; Anemia; Body Weight; Darbepoetin alfa; Dose-Response Relationship, Drug; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Treatment Outcome

Recombinant human erythropoietin (rHuEPO) is the standard of care for patients with chemotherapy-related anemia. Intravenous (IV) iron improves hemoglobin (Hb) response and decreases dosage requirements in patients with anemia of kidney disease, but its effect has not been studied in randomized trials in cancer patients.. This prospective, multicenter, open-label, randomized trial enrolled 157 patients with chemotherapy-related anemia (Hb

Topics: Abnormalities, Drug-Induced; Administration, Oral; Aged; Anemia; Antineoplastic Agents; Erythropoietin; Female; Humans; Infusions, Intravenous; Iron; Iron-Dextran Complex; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins

The role of nutrition in the palliative treatment of patients with malignancy-related cachexia is unclear. The goal of the current study was to determine whether specialized, nutrition-focused patient care could improve integrated whole-body metabolism and functional outcome in unselected weight-losing patients with malignant disease who were receiving systemic antiinflammatory (cyclooxygenase [COX]-inhibitory) treatment along with erythropoietin (EPO) support.. Three hundred nine patients with malignant disease who experienced progressive cachexia due to solid tumors (primarily gastrointestinal lesions) were randomized to receive a COX inhibitor (indomethacin, 50 mg twice daily) and EPO (15-40,000 units per week) along with specialized, nutrition-focused patient care (oral nutritional support and home total parenteral nutrition [TPN]) provided on a patient-by-patient basis to attenuate inflammation, prevent anemia, and improve nutritional status. Control patients received the same indomethacin and EPO doses that study patients received without the added nutritional support. All patients were treated and followed until death. Biochemical assays (blood, liver, kidney, and thyroid), nutritional state assessment (food intake and body composition), and exercise testing with simultaneous measurement of whole-body respiratory gas exchange before and during exercise were performed before the start of treatment and then at regular intervals during the treatment period (every 2-30 months after treatment initiation). Statistical analyses were performed on 'intention-to-treat' and 'as-treated' bases.. Home TPN was provided to approximately 50% of the study patients without severe complications. Over the entire observation period, rhEPO prevented the development of anemia in both study patients and control patients. Intention-to-treat analysis revealed an improvement in energy balance for nutritionally supported patients (P < 0.03); no other significant differences in outcome between study patients and control patients were observed. As-treated analysis demonstrated that patients receiving nutrition experienced prolonged survival (P < 0.01), which was accompanied by improved energy balance (P < 0.001), increasing body fat (P < 0.05), and a greater maximum exercise capacity (P < 0.04). A trend toward increased metabolic efficiency at maximum exercise (P < 0.06) for study patients relative to control patients also was observed.. The results of the current study strongly support that nutrition is a limiting factor influencing survival and that nutritional support protects integrated metabolism and metabolic function in patients with progressive cachexia secondary to malignant disease.

Topics: Aged; Analysis of Variance; Cachexia; Combined Modality Therapy; Energy Metabolism; Erythropoietin; Exercise Test; Female; Follow-Up Studies; Humans; Male; Neoplasms; Nutritional Support; Palliative Care; Probability; Prospective Studies; Prostaglandin-Endoperoxide Synthases; Quality of Life; Reference Values; Risk Assessment; Survival Analysis; Sweden; Terminally Ill

Epoetin alfa, administered at standard dosages of 10,000-20,000 IU three times weekly or 40,000-60,000 IU once weekly, has been shown to significantly increase hemoglobin (Hb) levels, decrease transfusion requirements, and improve quality-of-life parameters in patients undergoing chemotherapy.Objective. This open-label, nonrandomized, historically controlled study was conducted to evaluate the efficacy and safety of an induction dose of epoetin alfa in patients with moderate or severe anemia who were receiving chemotherapy.. Nineteen patients with solid tumors and Hb levels < 9.0 g/dl were enrolled. The patients received single s.c. injections of epoetin alfa, 40,000 IU, on study days 1, 4, 7, 10, and 13, and were then observed for the following 30 days. Nineteen other cancer patients who had matching characteristics and had received epoetin alfa, 10,000 IU, three times weekly for the 45-day study period, served as historical controls. The primary efficacy variable was change in Hb level from baseline to days 15 (approximately week 2) and 45 (approximately week 6.5). Secondary efficacy variables included the percent response (Hb increase > or = 1 g/dl) and percent major response (Hb increase > or = 2 g/dl) at days 15 and 45, the durations of response and major response after day 45, the proportion of patients transfused within the 45 study days, the changes in Eastern Cooperative Oncology Group performance status score at days 15 and 45, and the ability to maintain the planned chemotherapy dose (dose intensity) over the 45-day study.. Mean increases in Hb level in the epoetin alfa 40,000 IU group were significantly greater than those in the historical control group both at day 15 and at day 45. The increase in Hb level in the control group approximated increases reported with standard 3-times-weekly epoetin alfa at day 15 but was somewhat lower than the increases typically seen by day 45, presumably due to the fact that, in the present study, the epoetin alfa dose was not doubled in initial nonresponders, as is commonly done with standard epoetin alfa treatment. The rates of major response for epoetin alfa 40,000 IU patients (37% at day 15 and 84% at day 45) were higher than those for control patients (16% and 21%, respectively). Also, the transfusion rate was lower and performance status scores were better in the epoetin alfa 40,000 IU patients than in the control patients. In all, 74% of epoetin alfa 40,000 IU patients versus 47% of control patients received 100% of the planned chemotherapy dose. Epoetin alfa was well tolerated in both treatment groups.. Results of this study suggest that epoetin alfa at a dose of 40,000 IU administered five times over 2 weeks may confer even higher response rates than those seen with standard dosing regimens. These encouraging results support further study of the proposed induction dose of epoetin alfa in a larger, randomized, prospectively controlled trial.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Case-Control Studies; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Multivariate Analysis; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins; Remission Induction; Treatment Outcome

Autologous stem-cell transplantation has been shown to be a curative procedure for a variety of leukemias and lymphomas. Most transplants require RBC and platelet support. We report the ability to perform autologous transplantation without blood-product support.. In this study, we treated 26 patients with religious objection to blood products with autologous stem-cell support without the use of any blood products. Patients received a combination of granulocyte colony-stimulating factor (G-CSF), erythropoietin, and interleukin-11 or G-CSF alone to mobilize stem cells. Post-transplant patients received intravenous iron, erythropoietin, G-CSF, and epsilon aminocaproic acid.. There were two major bleeding complications (8%), with two treatment-related deaths (8%). There were three minor bleeding complications (12%). The median fall in hemoglobin level was 4.7 g/dL; the median hemoglobin level 30 days after transplantation was 9.2 g/dL. The median total number of days with platelet count less than 10 x 10(9)/L was 4 days; the median days to platelet recovery greater than 20 x 10(9)/L was 12 days.. Autologous stem-cell transplantation can be performed safely without the use of any blood products.

Topics: Adult; Combined Modality Therapy; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Hemorrhage; Humans; Interleukin-11; Jehovah's Witnesses; Leukocyte Count; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasms; Neutropenia; Peripheral Blood Stem Cell Transplantation; Platelet Count; Survival Rate; Transplantation, Autologous

Anemia, highly common among cancer patients, is often an underlying cause of cancer-related fatigue and other quality-of-life (QOL) deficits. Although randomized clinical trials have shown that treatment with epoetin alfa increases hemoglobin levels, reduces fatigue, lessens transfusion requirements, and improves overall QOL, cancer-related anemia and fatigue remain undertreated. This is, in part, because scales and measures of QOL are still relatively unfamiliar to most clinicians and because population-based reference ranges are lacking, thus making clinical trial results difficult to interpret.. To aid in the interpretation of QOL results from clinical trials, we administered the Functional Assessment of Cancer Therapy-Anemia (FACT-An) QOL instrument to a nationally representative sample of 1,400 people using an Internet survey panel in the United States. We then compared the FACT-An data from the Internet survey with the QOL data of a 375-patient randomized, double-blind clinical trial evaluating epoetin alfa versus placebo in anemic cancer patients.. FACT-An, as administered to the survey population, displayed good psychometric properties and was able to discriminate between respondents with histories of specified illnesses, including anemia and cancer, and those without. Comparison of the population norm and clinical trial data showed that treatment with epoetin alfa resulted in clinically meaningful as well as statistically significant improvements in QOL (P <.01).. Reliable population norm data are now available to aid in the interpretation of clinical trial results where the FACT-An questionnaire is administered. In the clinical trial, treatment with epoetin alfa overcame much of the QOL deficit seen in anemic cancer patients compared with the norm population sample.

Topics: Adolescent; Anemia; Blood Transfusion; Double-Blind Method; Epoetin Alfa; Erythropoietin; Fatigue; Health Status Indicators; Hematinics; Hemoglobins; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Surveys and Questionnaires; Treatment Outcome

Health-related quality of life (HrQOL) assessments are gaining importance as outcome measures in cancer clinical trials. A recently published clinical trial reported statistically significant (P<0.001) increases in haemoglobin (Hb) levels and significantly (P<0.01) increased HrQOL scores following the administration of recombinant human erythropoietin (r-HuEPO, epoetin alfa) versus placebo to anaemic cancer patients who received non-platinum chemotherapy. This study employed five cancer-specific HrQOL instruments. Hb and HrQOL data from this trial were analysed to estimate the minimally important difference (MID) in HrQOL measures that could be interpreted as clinically meaningful, with Hb level selected as the best external standard. Patients were assigned to two groups: improved (Hb increases of >/=1 g/dL) or stable (change in Hb of-1 g/dL to <1 g/dL). The MID was first determined as the difference between the mean changes in HrQOL in the improved group versus the stable group. By this analysis, the differences in HrQOL scores between the epoetin alfa group and the placebo group were clinically important for all Hb-sensitive, cancer-specific HrQOL evaluations. Linear regression analyses performed to provide estimates of the MID for specific values of Hb change confirmed that the differences in HrQOL scores between patient groups were clinically significant. These analyses were repeated using a data set from a separate clinical trial, which further supported the conclusion that observed HrQOL changes demonstrated in the multicentre, double-blind study were clinically important. These methods provide one means for interpreting the clinical relevance of changes in HrQOL evaluated in clinical trials.

Topics: Anemia; Antineoplastic Agents; Double-Blind Method; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Regression Analysis

Platinum compounds are commonly associated with significant anemia. Erythropoietin administration has been found effective in correcting anemia in patients with solid tumors receiving chemotherapy. We conducted a randomized, open label study to assess the efficacy of erythropoietin in preventing transfusions and significant anemia (hemoglobin <10 g/dl) in patients with solid tumors receiving platinum-based chemotherapy.. One hundred forty-four patients with hemoglobin <13 g/dl were included in this study (72 in each arm). Patients in the treatment arm received 10,000 U of recombinant human erythropoietin (rHuEPO) thrice weekly s.c. during platinum-based chemotherapy, while patients in the control arm received no treatment.. All patients were evaluable for efficacy. Transfusions were reduced by the administration of rHuEPO (15.3 vs. 33.3%, p = 0.019), and fewer patients developed significant anemia (16.6 vs. 45.8%, p < 0.0001). Subgroup analysis showed that patients with observed to predicted (O/P) serum erythropoietin levels 0.9 or non-responders.. rHuEPO at a dose of 10,000 U thrice weekly prevents transfusions and development of significant anemia in patients with solid tumors receiving platinum-based chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Hypochromic; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Erythropoietin; Female; Greece; Humans; Male; Middle Aged; Neoplasms; Organoplatinum Compounds; Prognosis; Prospective Studies; Quality of Life; Recombinant Proteins; Risk Factors; Treatment Outcome

Anemia in patients receiving chemotherapy can be ameliorated with recombinant human erythropoietin (rHuEPO), which is administered one to three times per week. Darbepoetin alpha, a new erythropoietic agent, has longer serum residence time, allowing it to be administered less frequently.. Patients (n = 127) were randomized to receive study drug for 12 weeks: either rHuEPO 40,000 U with escalations to 60,000 U for nonresponders or darbepoetin alpha at doses of 4.5 microg/kg per week until hemoglobin concentration >or= 12 g/dL, then 1.5 microg/kg per week (Group 1); 4.5 microg/kg per week for 4 weeks, then 2.25 microg/kg per week for 8 weeks (Group 2); or 4.5 microg/kg per week for 4 weeks, then 3.0 microg/kg every 2 weeks (Group 3). Efficacy was measured using the mean change in hemoglobin level, the proportion of patients achieving a hemoglobin response, the time to response, and the mean change in Functional Assessment of Cancer Therapy-Fatigue Scale scores. Safety was assessed by reports of adverse events.. Overall, after 4 weeks of treatment, the mean change (95% confidence interval [95%CI]) in hemoglobin concentration was 0.53 g/dL (95%CI, 0.05-1.02 g/dL), 0.70 g/dL (95%CI, 0.11-1.29 g/dL), and 0.90 g/dL (95%CI, 0.47-1.33 g/dL) in darbepoetin alpha Groups 1, 2, and 3, respectively, and 0.39 g/dL (95%CI, - 0.22-1.00 g/dL) in the rHuEPO group. By the end of the study, the mean change (95%CI) in hemoglobin concentration was 1.35 g/dL (95%CI, 0.67-2.02 g/dL), 1.35 g/dL (95%CI, 0.57-2.12 g/dL), and 1.28 g/dL (95%CI, 0.84-1.73 g/dL) in darbepoetin alpha Groups 1, 2, and 3, respectively, and 1.03 g/dL (95%CI, 0.53-1.53 g/dL) in the rHuEPO group. The early erythropoietic response in patients who were treated with darbepoetin alpha was associated with an early and maintained reduction in patient-reported fatigue. The adverse event profile was comparable with all doses of darbepoetin alpha and rHuEPO.. Darbepoetin alpha, given as a front-loaded dose for 4 weeks and followed by lower and/or less frequent doses, appears to be efficacious and may decrease the time to response relative to treatment with rHuEPO.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Darbepoetin alfa; Deoxycytidine; Docetaxel; Erythropoietin; Fatigue; Female; Gemcitabine; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Paclitaxel; Pilot Projects; Taxoids; Treatment Outcome

This open-label, prospective study was conducted to compare the impact of epoetin beta vs standard care on quality of life (QoL) in anaemic patients with lymphoid or solid tumour malignancies. A total of 262 anaemic patients (haemoglobin [Hb]or=2 g dl(-1) increase in Hb level without need of transfusion after the initial 4 weeks of treatment. Baseline to final visit changes in SF-36 PCS, FACT-F and VAS scores were significantly greater with epoetin beta than with standard care (P<0.05); changes in FACT-An subscale score tended to be greater with epoetin beta (P=0.076). Epoetin beta significantly increased Hb concentrations relative to standard care (responders: 47% vs 13%; P<0.001). Levels of endogenous erythropoietin <50 mIU ml(-1) were significantly predictive of response (OR 2.496, 95% CI: 1.21-5.13). Epoetin beta therapy significantly improves QoL compared with standard care in anaemic patients with solid tumours and lymphoid malignancies.

Topics: Adult; Aged; Aged, 80 and over; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins

The purpose of this study was to assess whether the administration of recombinant human erythropoietin (rHuEPO) would correct anemia and improve the quality of life (QOL) in cancer patients receiving chemotherapy. One hundred twenty-two patients with hemoglobin

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins

A multicentre study evaluated the efficacy and safety of darbepoetin alpha administered weekly (QW), every 3 weeks (Q3W), and every 4 weeks (Q4W) to anaemic patients with cancer not concurrently receiving chemotherapy or radiotherapy. The QW portion (n=102) was an open-label, sequential, dose-escalation design; cohorts received darbepoetin alpha QW by subcutaneous (s.c.) injection at 0.5, 1.0, 2.25, or 4.5 micro g kg(-1) week(-1) for 12 weeks. The 12-week placebo-controlled, double-blind Q3W (6.75 micro g kg(-1)) and Q4W (6.75 or 10.0 micro g kg(-1)) schedules (n=86), which enrolled different patients, took place after the QW schedule and were followed by a 12-week, open-label phase. Patients were evaluated for change in haemoglobin end points and red blood cell transfusions, serum darbepoetin alpha concentration, and safety. Selected domains of health-related quality of life (HRQOL) were measured. With QW dosing, at least 70% of each cohort had a haemoglobin increase from baseline of > or =2 g dl(-1) or a concentration > or =12 g dl(-1) (haematopoietic response). In the 4.5 micro g kg(-1) QW cohort, all patients achieved a haematopoietic response (100%; 95% confidence interval (CI)=100, 100). In the Q3W and Q4W schedules, all cohorts had at least 60% of patients who achieved a haematopoietic response. Darbepoetin alpha effectively increases haemoglobin concentration when given QW, Q3W, or Q4W. Less-frequent administration may benefit patients with chronic anaemia of cancer and their caregivers alike.

Topics: Aged; Anemia; Chronic Disease; Darbepoetin alfa; Drug Administration Schedule; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Treatment Outcome

The current study was performed to prospectively evaluate the effectiveness, clinical outcomes, and safety of once-weekly (QW) recombinant human erythropoietin (r-HuEPO [epoetin-alpha]) in anemic cancer patients with nonmyeloid malignancies who were receiving radiation therapy (RT) concomitantly or sequentially with chemotherapy (CT).. A total of 777 anemic patients (hemoglobin [Hb] < or = 11 g/dL) were enrolled in this multicenter, open-label, nonrandomized, 16-week study. Patients initially received epoetin-alpha at a dose of 40,000 units (U) subcutaneously QW, escalating to a dose of 60,000 U QW if the Hb increased to < or = 1 g/dL after 4 weeks. Endpoints were changes in hematologic and quality of life (QOL) parameters.. Among the 442 patients evaluable for hematologic response, the mean increase in Hb from baseline to the time of final evaluation was 1.9 +/- 1.8 g/dL (P < 0.05). An increase in Hb of > or = 2 g/dL, in the absence of blood transfusions, occurred in 68.3% of patients (278 of 407 patients) who were on the study for > or = 30 days. The overall response rate (Hb increase > or = 2 g/dL or Hb > or = 12 g/dL in the absence of blood transfusions) was 74.0% (301 of 407 patients). In 359 patients who were evaluable for QOL assessment, epoetin-alpha therapy was found to significantly (P < 0.05) improve mean Linear Analog Scale Assessment (LASA) scores for energy level, ability to perform daily activities, and overall QOL from baseline to the time of final evaluation. QW epoetin-alpha therapy was found to be well tolerated.. Treatment with QW epoetin-alpha was found to increase Hb levels, decrease transfusion requirements, and improve functional status and QOL in anemic patients with nonmyeloid malignancies who were receiving RT concomitantly or sequentially with CT. Clinical benefits and the safety profile of QW epoetin-alpha in this setting appear to be similar to those observed in anemic cancer patients receiving CT.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Quality of Life; Radiotherapy; Recombinant Proteins

This dose-finding, placebo-controlled study evaluated the safety and efficacy of darbepoetin alfa administered every 3 weeks (Q3W) to anaemic patients receiving chemotherapy. In part A, patients (haemoglobin 50% of patients achieving a haematopoietic response. Administration of darbepoetin alfa Q3W has a tolerable safety profile and effectively ameliorates anaemia due to chemotherapy.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Darbepoetin alfa; Dose-Response Relationship, Drug; Double-Blind Method; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Treatment Outcome

Quality of life (QOL) endpoints from a randomized, placebo-controlled trial of anemic cancer patients treated with nonplatinum-containing chemotherapy who received epoetin alfa or placebo were subjected to a sensitivity analysis. Three QOL instruments were used: the Functional Assessment of Cancer Therapy-Anemia (FACT-An), the Cancer Linear Analog Scale (CLAS), and the Medical Outcomes Study Short Form-36 (SF-36). The seven primary endpoints chosen a priori for analysis were: the Functional Assessment of Cancer Therapy-General (FACT-G) Total, FACT-An fatigue subscale, CLAS energy, CLAS daily activities, CLAS overall QOL, and the SF-36 physical and mental component summary scales. Lower QOL scores were reported for patients who discontinued early, suggesting a nonrandom dropout process. Significant correlations (ranging from 0.37 to 0.77) between individual rates of change and the time to early termination of therapy or death supported this conclusion. Estimates of within-treatment-arm QOL change over time are more conservative with the missing not at random (MNAR) assumption as compared with the more optimistic estimates with the assumption that missing QOL data are missing at random (MAR). However, the between-treatment-arm comparisons were consistent across analyses, demonstrating statistically significant differences in favor of the epoetin alfa arm for four of the seven outcome measures.

Topics: Aged; Anemia; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Placebos; Quality of Life; Recombinant Proteins; Sensitivity and Specificity; Surveys and Questionnaires; Treatment Outcome

In part A of this study, patients were randomised to cohorts receiving darbepoetin alfa at doses of 0.5 to 8.0 m.c.g x kg(-1) x wk(-1) or to a control group receiving epoetin alfa at an initial dose of 150 U x kg(-1) three times weekly. In part B, the cohorts were darbepoetin alfa 3.0 to 9.0 m.c.g x kg(-1) every 2 weeks or epoetin alfa, initial dose 40 000 U x wk(-1). Safety was assessed by adverse events, changes in blood pressure, and formation of antibodies to darbepoetin alfa. Efficacy was assessed by several haematologic endpoints, including change in haemoglobin from baseline. The adverse event profile of darbepoetin alfa was similar to that of epoetin alfa. No relationship between the rapidity of haemoglobin response and any adverse event was observed. No antibodies to darbepoetin alfa were detected. Higher doses of darbepoetin alfa increased the proportion of patients with a haemoglobin response and decreased the median time to response. The overall dose of darbepoetin alfa required to produce a mean increase in haemoglobin does not increase when the dosing interval is increased from 1 to 2 weeks. Therapy with darbepoetin alfa is safe and effective in producing a dose-related increase in haemoglobin levels in patients with cancer receiving chemotherapy.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Darbepoetin alfa; Dose-Response Relationship, Drug; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins

The efficacy and safety of epoetin alfa in ameliorating cancer- or chemotherapy-related anemia and reducing red blood cell (RBC) transfusion requirements have been demonstrated in numerous trials in adult patients. However, limited information is available about recombinant human erythropoietin (rHuEPO, epoetin alfa) as a treatment option in pediatric cancer patients.. To gain more information about the efficacy and safety of epoetin alfa in the treatment of chemotherapy-induced anemia in children with solid tumors receiving either platinum- or nonplatinum-containing chemotherapy, an 8-week randomized trial was conducted. Epoetin alfa 150 IU/kg was given 3 times a week for 8 weeks to 17 patients; 17 control patients received standard of care.. Transfusions, administered if the hemoglobin (Hb) level dropped to below 6 g/dL, were necessary for only one patient in the epoetin alfa group, as compared with eight patients in the control group (change in Hb from 8.5-10.21 g/dL in the epoetin alfa group vs. 8.48-8.41 g/dL in the control group).. The data from this study suggest that this dosing regimen of epoetin alfa is effective and safe in pediatric cancer patients with chemotherapy-related anemia. Further studies with epoetin alfa in more children with different chemotherapy regimens are needed.

Topics: Adolescent; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Child; Child, Preschool; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Infant; Injections, Subcutaneous; Male; Neoplasms; Recombinant Proteins; Treatment Outcome

Combination chemotherapy is often used for long periods in children with solid malignancies, leading to anemia and necessitating intervention with red blood cell (RBC) transfusions. Transfusions, however, are associated with a variety of adverse events and risks. Recombinant human erythropoietin (rHuEPO, epoetin alfa) has been shown to reduce the need for transfusions and to ameliorate the symptoms of anemia in adults, but few studies have been conducted thus far in pediatric patients.. Thirty-seven children with solid tumors receiving treatment with platinum- or nonplatinum-based chemotherapy were treated with epoetin alfa and supplemental iron in a single-center, open-label, 28-week, case-control study.. Epoetin alfa significantly reduced the need for RBC (P = 0.007) and platelet (P = 0.01) transfusions, and prolonged the time to first RBC transfusion (P = 0.0004) as compared to the control group. Moreover, epoetin alfa was effective in maintaining mean hemoglobin levels during the course of the study, whereas they declined below baseline after week 9 in the control group.. Epoetin alfa is effective and safe in reducing transfusion requirements and maintaining adequate hemoglobin levels in children with solid tumors undergoing combination chemotherapy.

Topics: Adolescent; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Child; Child, Preschool; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Infant; Injections, Intravenous; Injections, Subcutaneous; Male; Neoplasms; Recombinant Proteins; Treatment Outcome

The objectives of this study were to assess the safety and efficacy of darbepoetin alfa (Aranesp) administered every 2 weeks in anemic patients with solid tumors receiving chemotherapy. This was an open-label, randomized, active-controlled, multicenter dose-finding study evaluating a range of every-2-week darbepoetin alfa doses. The active control arm received epoetin alfa (Epogen, Procrit) at 40,000 U weekly with a dose increase to 60,000 U weekly for subjects with an inadequate response. The lowest clinically effective doses of darbepoetin alfa in this study were 3.0 and 5.0 microg/kg every 2 weeks, with no additional benefit observed at higher doses. The percentage of patients who achieved a hematopoietic response in the 3.0- and 5.0-microg/kg groups was 66% (95% confidence interval [CI] = 46%-86%) and 84% (95% CI = 67%-100%), respectively, compared with 63% (95% CI = 46%-81%) in the epoetin alfa group. Darbepoetin alfa administered at a dose of 3.0 microg/kg every 2 weeks is safe and effective for treating anemia in patients with solid tumors on chemotherapy, and is comparable to epoetin alfa. A dose increase to 5.0 microg/kg of darbepoetin alfa administered every 2 weeks may be appropriate in patients with an inadequate initial response.

Topics: Anemia; Breast Neoplasms; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Gastrointestinal Neoplasms; Genital Neoplasms, Female; Genital Neoplasms, Male; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Recombinant Proteins; Treatment Outcome

Cancer-related anaemia is associated with a wide spectrum of symptoms that can negatively affect quality of life. Because epoetin alfa has demonstrated efficacy in correcting cancer-related anaemia, the impact of this treatment on quality of life was evaluated in a multinational, randomised, double-blind, placebo-controlled trial in 375 anaemic cancer patients receiving non-platinum-based chemotherapy. The cancer-specific measures of quality of life included the general scale (FACT-G Total) and fatigue subscale (FACT-An Fatigue subscale) of the Functional Assessment of Cancer Therapy-Anaemia and the Cancer Linear Analogue Scales measuring energy, ability to do daily activities, and overall quality of life. These measures were also used to examine the relationship between haemoglobin levels and quality of life. Both univariate and multiple linear regression analyses of quality of life data were performed. Results of the univariate analysis have been reported previously. The a priori-planned multiple linear regression analysis, which accounted for the effects of disease progression and several other possibly confounding variables on quality of life, showed a significant advantage for epoetin alfa over placebo for the five scales (all, P<0.05), and confirmed the results of the univariate analysis. For cancer-specific measures, significant correlations were demonstrated between baseline haemoglobin and quality of life (r, range: 0.14-0.26, all P<0.05) and between change in haemoglobin and change in quality of life (r, range: 0.26-0.34, all P<0.01). These findings provide evidence that increasing haemoglobin levels by epoetin alfa administration can significantly improve cancer patients' quality of life.

Topics: Activities of Daily Living; Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins; Survival Rate; Treatment Outcome

Topics: Activities of Daily Living; Adolescent; Anemia; Antineoplastic Agents; Blood Transfusion; Double-Blind Method; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Treatment Outcome

In a single-center, case-control study the authors evaluated the efficacy and safety of epoetin alfa in pediatric cancer patients receiving platinum- or nonplatinum-based chemotherapy. Thirty-seven patients with solid tumors received epoetin alfa 3 times weekly at a dose of 150 IU/kg (hemoglobin [Hb] > or = 12 g/dL and < or = 16 g/dL) or 300 IU/kg (Hb) < 12 g/dL) for 28 weeks. Data from treated patients were compared to data from 37 untreated control patients. Significant between-group differences in favor of the epoetin alfa-treated Patients were observed in overall red blood cell transfusion requirements (p = .007) and overall platelet transfusion requirements (p = .010). Additionally, significant between-group differences favoring epoetin alfa were seen by Kaplan-Meier plots, estimating mean time to first red blood cell transfusion (p = .0004). Mean Hb (g/dL) was maintained at baseline levels in the epoetin alfa group for most of the course of the study. No drug-related adverse events were seen in epoetin alfa-treated patients.

Topics: Adolescent; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Case-Control Studies; Child; Child, Preschool; Drug Interactions; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Infant; Male; Neoplasms; Platinum Compounds; Recombinant Proteins; Therapeutic Equivalency; Time Factors

Data from two large, community-based clinical trials that evaluated the efficacy of epoetin alfa in anemic cancer patients receiving chemotherapy were retrospectively analyzed to determine if clinical outcomes were different depending on whether chemotherapy was platinum- or nonplatinum-based.. Patients received epoetin alfa 150-300 IU/kg (Glaspy: Study 1; n = 2,342) or 10,000-20,000 IU (Demetri: Study 2; n = 2,370) s.c. three times each week for 4 months. Efficacy end points were changes in transfusion requirements, hemoglobin (Hb) levels, and quality of life (QOL). A total of 4,298 out of 4,712 patients (platinum-based, n = 1,601; nonplatinum-based, n = 2,697), who both received chemotherapy and had available data, were eligible for this retrospective analysis.. Baseline characteristics across groups were comparable with few exceptions, which were anticipated in view of the characteristics of the two different chemotherapy types. Decreases in transfusion requirements after 2, 3, and 4 months were significant, regardless of chemotherapy type. Mean increases in Hb level from baseline to final evaluation ranged from 1.6 g/dl to 2.0 g/dl across study groups and were significant, regardless of chemotherapy type. QOL, as measured by the Linear Analog Scale Assessment (LASA), improved significantly by 20%-43%, regardless of chemotherapy type, and improvements were associated with increases in Hb. Epoetin alfa was well tolerated in both studies, regardless of chemotherapy type.. Treatment of anemic cancer patients with epoetin alfa results in significant reduction in transfusion requirements, increase in Hb levels, and improvements in QOL, regardless of whether the chemotherapy is platinum- or nonplatinum-based.

Topics: Anemia; Blood Transfusion; Disease Progression; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hematologic Neoplasms; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Platinum; Predictive Value of Tests; Prognosis; Quality of Life; Recombinant Proteins; Retrospective Studies; Sensitivity and Specificity; Time Factors; Treatment Outcome

The use of human recombinant erythropoietin (rHuEpo) has been approved by the Food and Drug Administration (FDA) in patients with anemia and cancer. Although good results have been obtained, it is too expensive to permit its use massively. For the purpose of evaluating the therapeutic effect of rHuEpo, including toxicity, predictive response variables and quality of life parameters, a prospective trial was carried out in patients with anemia and cancer. Hematimetric parameters, ferritin, Epo, cytokines, transfusions and quality of life were registered. A total of 36 patients were treated in the protocol (34 were evaluable): 16 men and 20 women, with a medium age 56.4 years; 27 patients were treated with chemotherapy (16 with cisplatinum); 15 patients presented medullar infiltration. In 73.5% patients an increase in the level of hemoglobin was registered, and in 64.7% its normalisation was attained. Transfusional requirements were reduced by 50%. The hemoglobin increase greater than 0.5 g/dl at the second week of treatment was the most significant variable of early response. Patients treated with cisplatinum, seric ferritin lower than 1,100 ng/dl and those without medullar tumoral infiltration responded best. Serum Epo, cytokines (IL-1, IL-6 and TNF) and reticulocyte count at the second week did not correlate with response. Quality of life parameters were better in patients with good response to rHuEpo. It can be concluded that good results in the treatment of patients with anemia and cancer are obtained with rHuEpo.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Anemia; Chi-Square Distribution; Dose-Response Relationship, Drug; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins; Treatment Outcome

A controlled clinical trial was conducted to evaluate the use of epoetin alfa in cachectic patients with solid tumors who were not receiving chemotherapy to determine if increasing hemoglobin (Hb) resulted in increased exercise capacity, metabolism, and energy efficiency during a maximum work load. The randomized, prospective study included 108 patients who received oral indomethacin 50 mg twice daily (n = 58; control group), or oral indomethacin 50 mg twice daily with epoetin alfa 4,000 to 10,000 IU by subcutaneous injection 3 times weekly (n = 50; study group). Patients randomized to the study group received epoetin alfa only when Hb decreased below 12.8 g/dL for men and 12.0 g/dL for women. Mean Hb levels in the study group were significantly (P <.0001) improved overall compared with the control group, with significant differences seen between groups after 2 to 4 months (P <.003), 6 to 8 months (P <.01), and 10 to 30 months (P <.01). Mean inflammatory variables including serum albumin, erythrocyte sedimentation rate, and C-reactive protein were significantly (P <.02) changed in the study group compared with the control group (ie, the control group had more inflammation). Significantly lower mean body weight (P <.05) and resting energy expenditure (P <.007) were recorded for patients in the control group versus the study group. The study group showed significantly greater mean exercise capacity (P <.0001), mean oxygen uptake (P <.01), mean CO(2) production (P <.009), and respiration (P <.03). These results demonstrate that early use of epoetin alfa prevents anemia in patients with progressive cancer who are not receiving chemotherapy. Normalization of Hb levels resulted in improved whole-body metabolism and energy efficiency, which is associated with greater exercise capacity and better daily quality of life.

Topics: Aged; Anemia; Anti-Inflammatory Agents, Non-Steroidal; Cachexia; Cyclooxygenase Inhibitors; Energy Metabolism; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Indomethacin; Male; Middle Aged; Neoplasms; Physical Exertion; Prospective Studies; Quality of Life; Recombinant Proteins

A prospective open-label study was designed to evaluate the safety, efficacy, and impact on quality of life of recombinant human erythropoietin (rHuEPO, epoetin alfa) therapy for cancer-related anemia. Of the 401 patients enrolled at 34 centers from across Canada, a cohort of 183 patients did not receive chemotherapy during the 16-week study period. All patients received epoetin alfa 150 IU/kg subcutaneously 3 times per week. The dose was increased to 300 IU/kg if the hemoglobin level did not increase by at least 1.0 g/dL after 4 weeks. Epoetin alfa therapy significantly increased hemoglobin levels and reduced transfusion requirements. Moreover, epoetin alfa provided statistically significant and clinically meaningful improvements in quality of life as measured by the Functional Assessment of Cancer Therapy-Anemia and Linear Analog Scale Assessment (also known as Cancer Linear Analog Scale). Increases in hemoglobin were correlated significantly with improvements in quality of life as well as Eastern Cooperative Oncology Group performance status. Treatment with epoetin alfa was well tolerated. These results demonstrate that epoetin alfa therapy is effective and safe in cancer patients with anemia, regardless of whether they are or are not receiving chemotherapy.

Topics: Aged; Anemia; Blood Transfusion; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins; Sickness Impact Profile

Anaemia is a common occurrence in patients with cancer, and currently can be treated in several ways. Novel erythropoiesis stimulating protein (NESP, darbepoetin alfa) was created using site-directed mutagenesis to have 8 more sialic acid side chains than recombinant human erythropoietin (rHuEPO). The additional sialic acid content has resulted in an approximately 3-fold greater half-life relative to rHuEPO in patients with chronic renal failure. This study evaluates the pharmacokinetic profile of NESP in patients receiving multiple cycles of chemotherapy. Anaemic patients (haemoglobin < or = 11.0 g dl(-1)) who had non-myeloid malignancies received NESP weekly (2.25 mcg kg(-1) wk(-1)) under the supervision of a physician, starting on day 1 of chemotherapy for 3 chemotherapy cycles given at 3-week intervals. Blood samples were collected during chemotherapy cycles 1 and 3 for pharmacokinetic analysis. All patients were followed for 4 weeks after treatment. NESP was well tolerated by all patients. After a single dose during chemotherapy cycle 1, pharmacokinetic parameters (mean (SD), n) for the first 15 patients were: T(max)86.1 (22.8) h (n = 14); C(max)9.0 (5.1) ng ml(-1)(n = 14); t(1/2,z)32.6 (11.8) h (n = 7); CL/F 3.7 (1.0) ml h(-1) kg(-1)(n = 7). The subjects for whom all parameters could be calculated may represent a sub-group of the entire population. Similar results were obtained in cycle 3. In addition, haemoglobin response data suggests that, in this patient population, dosing less frequently than the 3 times weekly doses used for rHuEPO may be possible while improving anaemia.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Darbepoetin alfa; Drug Administration Schedule; Drug Interactions; Erythropoiesis; Erythropoietin; Female; Half-Life; Hemoglobins; Humans; Injections, Subcutaneous; Male; Middle Aged; N-Acetylneuraminic Acid; Neoplasms; Recombinant Proteins; Safety

Darbepoetin alfa is a novel erythropoiesis stimulating protein (NESP), which stimulates erythropoiesis by the same mechanism as recombinant human erythropoietin (rHuEPO). NESP has been shown to be safe and efficacious in patients with chronic renal failure. NESP is biochemically distinct from rHuEPO, due to its increased sialic acid content. NESP has an approximately 3-fold greater half-life. rHuEPO has been shown to be safe and effective for the treatment of chemotherapy-induced anaemia. This study assessed the safety and efficacy of NESP administered once per week, under the supervision of a physician, to patients with solid tumours who were receiving multicycle chemotherapy for up to 12 weeks. Three dose cohorts are presented in this sequential, unblinded and dose-escalating study. Thirteen to 59 patients received NESP (0.5, 1.5 or 2.25 mcg kg(-1)wk(-1)) in each cohort. Patients were monitored for adverse events, including antibody formation to NESP and for effects on haemoglobin. NESP appeared to be well tolerated. Adverse events were similar across all cohorts and were consistent with the population being studied. No antibody formation was detected over the 16-week study period and follow-up. A dose-response relationship was evident for NESP and multiple measures of efficacy, including proportion of patients responding to NESP and the mean change in haemoglobin by week 4 and end of treatment for NESP 0.5, 1.5 and 2.25 mcg kg(-1)wk(-1)cohorts (mean change in haemoglobin at end of treatment was 1.24, 1.73 and 2.15 g dl(-1)respectively). Controlled studies of this agent at higher doses and less frequent schedules of administration are ongoing.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Cohort Studies; Combined Modality Therapy; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Female; Half-Life; Hemoglobins; Humans; Injections, Subcutaneous; Male; Middle Aged; N-Acetylneuraminic Acid; Neoplasms; Recombinant Proteins; Safety; Treatment Outcome

Anaemia is a common haematologic disorder in patients with cancer and has a multifactorial aetiology, including the effects of the malignancy itself and residual effects from previous therapy. Novel erythropoiesis stimulating protein (NESP, darbepoetin alfa), a protein with additional sialic acid compared with erythropoietin (EPO), stimulates erythropoiesis by the same mechanism as recombinant human erythropoietin (rHuEPO) but it is biochemically distinct. NESP, with its approximately 3-fold greater serum half-life, can maintain haemoglobin levels as effectively as rHuEPO in anaemic patients with chronic renal failure and do so with less frequent dosing. We investigated the ability of NESP to safely increase haemoglobin levels of anaemic patients with non-myeloid malignancies not receiving chemotherapy. NESP was administered under the supervision of a physician at doses of 0.5, 1.0, 2.25 or 4.5 mcg kg(-1)wk(-1)for a maximum of 12 weeks. This report includes 89 patients completing the study by November 2000. NESP was well tolerated, with no reported dose-limiting toxicities or treatment-related severe adverse events. Increasing doses of NESP corresponded with increased efficacy. The percentage (95% confidence interval) of patients responding ranged from 61% (42%, 77%) in the 1.0 mcg kg(-1)wk(-1)group to 83% (65%, 94%) in the 4.5 mcg kg(-1)wk(-1)group.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Fatigue; Female; Half-Life; Hemoglobins; Humans; Injections, Subcutaneous; Life Tables; Male; Middle Aged; N-Acetylneuraminic Acid; Neoplasms; Quality of Life; Recombinant Proteins; Safety; Treatment Outcome

To compare the need for blood transfusions between two groups of patients treated with cisplatin-containing chemotherapy. One of these groups received epoetin alpha therapy.. Prospective with an historical control group.. From April 1998 to December 1999, 44 patients who were being treated with cisplatin and gemcitabine were also administered epoetin alpha (10,000 U subcutaneously, thrice weekly) from the onset of anaemia. The need for red blood cell transfusions in this group was compared to a historical control group of 46 patients treated with the same combination chemotherapy regimen from November 1995 to July 1997.. In the historical control group, each patient received an average of 1.6 red blood cell transfusions as compared to 0.7 in the epoetin alpha group (a 58% reduction). The average number of units of red blood cells transfused per patient was 3.6 for the control group and 1.8 for the epoetin alpha group (a 50% reduction). In the epoetin alpha group, none of the patients received more than 2 transfusions whereas in the control group, 10 patients (22%) received 3 or more transfusions. In two patients, epoetin therapy had to be stopped due to the occurrence of hypertension.. Epoetin alpha reduced the need for red blood cell transfusions during cisplatin-containing chemotherapy. Its toxic effect was minimal.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Cisplatin; Deoxycytidine; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Female; Gemcitabine; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Treatment Outcome

This randomized, double-blind, placebo-controlled clinical trial assessed the effects of epoetin alfa on transfusion requirements, hematopoietic parameters, quality of life (QOL), and safety in anemic cancer patients receiving nonplatinum chemotherapy. The study also explored a possible relationship between increased hemoglobin and survival.. Three hundred seventy-five patients with solid or nonmyeloid hematologic malignancies and hemoglobin levels < or = 10.5 g/dL, or greater than 10.5 g/dL but < or = 12.0 g/dL after a hemoglobin decrease of > or = 1.5 g/dL per cycle since starting chemotherapy, were randomized 2:1 to epoetin alfa 150 to 300 IU/kg (n = 251) or placebo (n = 124) three times per week subcutaneously for 12 to 24 weeks. The primary end point was proportion of patients transfused; secondary end points were change in hemoglobin and QOL. The protocol was amended before unblinding to prospectively collect and assess survival data 12 months after the last patient completed the study.. Epoetin alfa, compared with placebo, significantly decreased transfusion requirements (P =.0057) and increased hemoglobin (P <.001). Improvement of all primary cancer- and anemia-specific QOL domains, including energy level, ability to do daily activities, and fatigue, was significantly (P <.01) greater for epoetin alfa versus placebo patients. Although the study was not powered for survival as an end point, Kaplan-Meier estimates showed a trend in overall survival favoring epoetin alfa (P =.13, log-rank test), and Cox regression analysis showed an estimated hazards ratio of 1.309 (P =.052) favoring epoetin alfa. Adverse events were comparable between groups.. Epoetin alfa safely and effectively ameliorates anemia and significantly improves QOL in cancer patients receiving nonplatinum chemotherapy. Encouraging results regarding increased survival warrant another trial designed to confirm these findings.

Topics: Activities of Daily Living; Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Blood Transfusion; Double-Blind Method; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Placebos; Quality of Life; Recombinant Proteins; Survival Analysis; Treatment Outcome

To prospectively evaluate the effectiveness, safety, and clinical benefits of once-weekly epoetin alfa therapy as an adjunct to chemotherapy in anemic cancer patients.. A total of 3,012 patients with nonmyeloid malignancies who received chemotherapy were enrolled onto this multicenter, open-label, nonrandomized study conducted in 600 United States community-based practices. Patients received epoetin alfa 40,000 U once weekly, which could be increased to 60,000 U once weekly after 4 weeks dependent on hemoglobin response. Treatment was continued for a maximum of 16 weeks.. Among the 2,964 patients assessable for efficacy, epoetin alfa therapy resulted in significant increases in hemoglobin levels, decreases in transfusion requirements, and improvements in functional status and fatigue as assessed by the linear analog scale assessment (energy level, ability to perform daily activities, and overall quality of life) and the anemia subscale of the Functional Assessment of Cancer Therapy-Anemia questionnaire. Improvements in quality-of-life parameters correlated significantly (P <.001) with increased hemoglobin levels. The direct relationship between hemoglobin and quality-of-life improvement was sustained during the 16-week study period, which is similar to findings of large community-based trials of three-times-weekly dosing. Once-weekly epoetin alfa was well tolerated, with most adverse events attributed to the underlying disease or concomitant chemotherapy.. The results from this large, prospective, community-based trial suggest that once-weekly epoetin alfa therapy increases hemoglobin levels, decreases transfusion requirements, and improves quality of life in patients with cancer and anemia who undergo concomitant chemotherapy. Based on the results of this study, the clinical benefits and the adverse event profile of once-weekly epoetin alfa therapy in community-based practice are similar to those observed in the historical experience with the three-times-weekly dosage schedule.

Topics: Activities of Daily Living; Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Blood Transfusion; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins; Treatment Outcome

To evaluate efficacy, safety, and quality of life (QOL) changes with epoetin alfa therapy for anemia in patients with nonmyeloid malignancies.. Anemic cancer patients were enrolled onto this prospective, open-label study from 34 centers across Canada. The trial had two cohorts: patients who were and were not receiving chemotherapy during the 16-week study. All patients initially received epoetin alfa 150 IU/kg subcutaneously three times per week. The dose was doubled after 4 weeks for patients who did not experience sufficient response.. Of the 183 patients enrolled in the nonchemotherapy cohort, statistically significant and clinically relevant improvements in QOL were observed with epoetin alfa therapy using both the FACT-An questionnaire and linear analog scale assessment. Hemoglobin levels increased significantly (P <.001; mean increase 2.5 g/dL from baseline to end of study) and these increases were positively correlated with improved QOL and change in Eastern Cooperative Oncology Group (ECOG) scores. There was a significant reduction in the percentage of patients who required blood transfusions. The 218 patients in the chemotherapy cohort also experienced significant improvements in QOL, decreased transfusion use, and increased hemoglobin levels that correlated with QOL improvements and change in ECOG scores. Epoetin alfa was well-tolerated in both cohorts.. Epoetin alfa administered to patients with cancer-related anemia for up to 16 weeks resulted in significantly improved QOL, increased hemoglobin levels, and decreased transfusion use. These benefits were observed in cancer patients who were not receiving chemotherapy as well as those who were.

Topics: Aged; Anemia; Antineoplastic Agents; Blood Transfusion; Epoetin Alfa; Erythropoietin; Female; Health Status Indicators; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins

Almost one cancer patient in two is anemic, with a correspondingly poorer prognosis and quality of life. A low blood hemoglobin level seems to directly impair treatment efficacy, particularly of radiotherapy, possibly because low tissue oxygenation causes a decrease in radiosensitivity. Tissue hypoxia may also facilitate tumor progression and impair the efficacy of cytostatic drugs. This constitutes a powerful rationale for correcting cancer anemia. Red cell transfusion is immediately effective, but carries risks of infection and immunosuppression. A safer alternative is recombinant human erythropoietin (rhEPO), which has already proved feasible and effective in correcting anemia and improving quality of life of cancer patients. Several ongoing radiotherapy studies are presently investigating whether rhEPO conclusively increases cancer cure rates. First results should be available in 2001. Given the efficacy of rhEPO to stimulate erythropoiesis and improve quality of life of cancer patients and its potential to enhance radiation's efficacy seem to earn it a firm place at least in the radiooncologist's arsenal.

Topics: Anemia; Cell Hypoxia; Clinical Trials as Topic; Erythropoietin; Humans; Neoplasms; Recombinant Proteins; Risk Factors; Treatment Outcome; Tumor Cells, Cultured

Anemia is a common side effect of anticancer chemotherapy. Blood transfusion, previously the only available treatment for chemotherapy-induced anemia, may result in some clinical or subclinical adverse effects in the recipients. Recombinant human erythropoietin (rhEPO) provides a new treatment modality for chemotherapy-induced anemia.. To evaluate the effect of rhEPO on the need for blood transfusions and on hemoglobin (Hb) concentrations, 227 patients with solid tumors and chemotherapy-induced anemia were enrolled in a randomized, controlled, clinical trial. Of 189 patients evaluable for efficacy, 101 received 5000 IU rhEPO daily s.c., while 88 patients received no treatment during the 12-week controlled phase of the study.. The results demonstrate a statistically significant reduction in the need for blood transfusions (28% vs. 42%, P = 0.028) and in the mean volume of packed red blood cells transfused (152 ml vs. 190 ml, P = 0.044) in patients treated with rhEPO compared to untreated controls. This effect was even more pronounced in patients receiving platinum-based chemotherapy (26% vs. 45%, P = 0.038). During the controlled treatment phase, the median Hb values increased in the rhEPO patients while remaining unchanged in the control group. The response was seen in all tumor types.. RhEPO administration at a dose of 5000 IU daily s.c. increases hemoglobin levels and reduces transfusion requirements in chemotherapy-induced anemia, especially during platinum-based chemotherapy.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Carboplatin; Cisplatin; Erythrocyte Count; Erythropoietin; Female; Hemoglobins; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Prognosis; Recombinant Proteins; Statistics, Nonparametric; Treatment Outcome

The purpose of this study was to determine the safety, efficacy and impact on quality of life of recombinant human erythropoietin (r-HuEPO) for cancer patients undergoing radiotherapy (RT). An open-labelled randomized design was used, with patients randomized to either treatment or control arms. Patients in the treatment arm received r-HuEPO given by subcutaneous injection at a dose of 200 units kg(-1) day(-1) plus oral iron supplements (ferrous sulphate 325 mg p.o. t.i.d.). Entry was restricted to patients with carcinoma of the lung, uterine cervix, prostate or breast who presented for RT with anaemia parameters reflective of 'the anaemia of chronic disease'. Radiotherapy policies (portals, doses, fraction size, etc.) were determined by the site and stage of disease. Complete blood counts (CBCs) were obtained weekly. The target level of haemoglobin was 15 g dl(-1) for men and 14 g dl(-1) for women. Quality of life (QOL) was assessed weekly by using an analogue scale to judge energy, activities of daily living and overall quality of life. Forty-eight patients were entered in the study, 24 in the treatment arm and 24 in the control arm. The prerandomization demographic characteristics and mean laboratory values were comparable in both arms. The mean haemoglobin at completion was 13.6 g dl(-1) for r-HuEPO-treated patients compared with 11.0 g dl(-1) for control subjects (P = 0.0012). Patients who received r-HuEPO demonstrated a mean weekly haemoglobin increase of 0.41 g dl(-1) compared with a decrease in mean haemoglobin level in controls for 6 of the 7 weeks of the study (mean weekly decrease of 0.073 g dl(-1)). Target levels of haemoglobin were achieved by 41.6% of r-HuEPO-treated patients compared with none of the control subjects. The mean platelet count declined in both arms of the study with RT but the decline from pretreatment was less rapid in r-HuEPO-treated patients (11.2% decrease) compared with controls (26.3% decrease) and was statistically significant during weeks 4-6. Toxicity was minor with only mild irritation at the injection site. Mean quality of life end points were superior in the treatment arm but not statistically significant. r-HuEPO had a beneficial effect on weekly haemoglobin levels in patients undergoing RT with response rates similar to other studies. There was also a less rapid decline in weekly platelet counts in r-HuEPO-treated patients compared with control subjects. Further studies are needed to address the optimum dose and

Topics: Anemia; Erythropoietin; Female; Hemoglobins; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins

Patients with cancer have inappropriately low levels of endogenous erythropoietin for the degree of anemia and further suppression of erythropoiesis results from chemotherapy. Patients with lung cancer, in particular, require a high frequency of transfusions, as they are unable to tolerate the symptoms of anemia due to their underlying pulmonary disease and, often, their age. Data from phase I and II trials indicated that epoetin alfa could increase hemoglobin concentration and reduce transfusion requirements. The beneficial response was dose dependent. These findings were confirmed in a series of three double-blind, placebo-controlled, multicenter phase III trials. Clinical trial evidence indicates that 150 IU/kg epoetin alfa three times weekly effectively treats anemia and decreases transfusion requirements in most cancer patients after the first month of chemotherapy. Furthermore, epoetin alfa will reduce the degree of anemia and markedly reduce the need for transfusions, thereby preventing anemia in patients undergoing multiple cycles of platinum-based combination chemotherapy. Epoetin alfa is well tolerated and shows marked activity in preventing anemia and reducing blood transfusion requirements in patients undergoing cyclic chemotherapy.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

Cancer is frequently associated with anemia and may be related to inadequate erythropoietin production. The objective of this study was to assess the efficacy and safety of recombinant human erythropoietin (r-HuEPO) in increasing hemoglobin levels and reducing the need of blood transfusions in children with cancer, as well as to identify predictors of the response to r-HuEPO.. A pilot trial was performed including 25 patients with solid malignant tumors receiving cyclic chemotherapy, r-HuEPO was administered subcutaneously, 150 U/kg/day 5 times a week for 12 consecutive weeks. Response was defined as the achievement of a Hb increase of at least 2 g/dl without blood transfusions. Patients were compared to history matched controls.. Baseline parameters were similar (p > 0.05) in both groups. The mean Hb increase was greater in the r-HuEPO group compared to controls (2.6 vs 0.1 g/dl; p < 0.001) and the mean units of blood transfused were lower in treated patients (0.32 vs 2.36; p < 0.05). Response to r-HuEPO was achieved in 19 (76%) patients. Low baseline erythropoietin levels and an increase in Hb of at least 0.5 g/dl after 3-4 weeks of treatment defined a greater probability of response. No serious adverse effects were observed.. r-HuEPO treatment represents a safe and effective means of increasing Hb levels and reducing blood requirements in pediatric cancer patients receiving chemotherapy and the prediction of response may be based on baseline serum erythropoietin levels and on the variation of Hb levels after 3-4 weeks of treatment.

Topics: Adolescent; Anemia; Antineoplastic Agents; Child; Disease Progression; Erythropoietin; Female; Hemoglobins; Humans; Male; Neoplasms; Pilot Projects; Prognosis; Recombinant Proteins; Treatment Outcome

This study was aimed at evaluating whether anemia could be prevented in unselected weight-losing cancer patients on anti-inflammatory treatment by early and prophylactic treatment with recombinant human erythropoietin (rhEPO) and whether such a benefit could be translated into improved physical function and metabolic efficiency. One hundred eight cancer patients who experienced progressive cachexia due to solid, mainly gastrointestinal tumors were randomized to receive twice daily a cyclo-oxygenase inhibitor (controls; indomethacin, 50 mg twice a day) or indomethacin and erythropoietin, provided on individual basis to prevent development of progressive anemia (study patients; indomethacin, 50 mg twice a day plus rhEPO; range, 12,000-30,000 units per week). All patients were treated and followed up until death or to preterminal stage. Biochemical tests (blood, liver, kidney, and thyroid), nutritional state assessment (food intake and body composition), and exercise testing with simultaneous measurements of respiratory gas exchanges before and during exercise were performed before institution of treatments and then at regular intervals during the treatment period (2-30 months after start). Study and control patients did not differ in survival. rhEPO prevented development of anemia during the entire observation period. This was associated with a significantly more preserved maximum exercise capacity in study patients compared to control patients during the follow-up period (101 +/- 10 versus 66 +/- 6 W; P < 0.0001), based on more effective ventilation and whole-body respiratory gas exchanges. These improvements were also evident when exercise performance was normalized to lean body mass, an indirect measure of the skeletal muscle mass. The metabolic efficiency, expressed as oxygen uptake per watt produced, was also significantly preserved in rhEPO-treated patients compared to controls (14.1 +/- 1.1 versus 16.3 +/- 0.9 ml O2/W, P < 0.05). Our results demonstrate that institution of early and prophylactic rhEPO treatment to patients with progressive cancer prevents development of tumor-induced anemia. This achievement was associated with a better preserved exercise capacity, which is explained in part by improved whole-body metabolic and energy efficiency during work load.

Topics: Aged; Anemia; Anti-Inflammatory Agents, Non-Steroidal; Cachexia; Cyclooxygenase Inhibitors; Energy Metabolism; Erythropoietin; Exercise Test; Female; Humans; Indomethacin; Male; Middle Aged; Neoplasms; Prospective Studies; Pulse; Recombinant Proteins; Weight Loss

Anemia, one of the most common complications of cancer chemotherapy, has been managed with red blood cell (RBC) transfusions. As an alternative, the agent epoetin alfa has the potential to reduce the transfusion requirements of patients receiving cancer chemotherapy. To estimate the value that cancer patients place on the drug, an economic analysis using the concept of willingness to pay (WTP) was conducted.. The method of WTP was used within the framework of a classical cost-benefit analysis to estimate the net cost or benefit of administering prophylactic epoetin alfa to cancer patients. This estimate included the direct cost of epoetin alfa administration and savings secondary to reduced RBC transfusions. A cohort of 100 cancer patients who received or were scheduled to receive cisplatin or noncisplatin chemotherapy (50 per group) were then interviewed to measure the maximum WTP (net benefit) that they experienced with epoetin alfa.. Regarding the benefits they would experience after 3 months of epoetin alfa administration, patients receiving cisplatin and noncisplatin therapy stated that they would be willing to pay an average of 587 U.S. dollars (U.S.$587) (95%CI: $300-$875) and U.S.$613 (95%CI: $324-$902), respectively. These benefits were then subtracted from the total cost of the drug when administered to patients receiving cisplatin (U.S.$3530) and noncisplatin (U.S.$3653) therapy. This produced a net incremental treatment cost of U.S.$2943 (95%CI: $2655-$3230) and U.S.$3039 (95%CI: $2750-$3328) for the respective treatment groups.. The results of the current study suggest that the routine administration of epoetin alfa to cancer patients receiving myelosuppressive chemotherapy is a highly resource-intensive treatment policy with modest benefit to patients. Additional research is required to identify high risk patient subgroups who would benefit most from the drug. [See editorial on pages 2427-9, this issue.]

Topics: Anemia; Antineoplastic Agents; Cisplatin; Cost-Benefit Analysis; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Health Services Needs and Demand; Hematinics; Humans; Income; Life Expectancy; Male; Middle Aged; Multivariate Analysis; Neoplasms; Prescription Fees; Recombinant Proteins; Sensitivity and Specificity; Socioeconomic Factors

The efficacy and safety of recombinant human erythropoietin (rhEPO) were tested when given subcutaneously (s.c.) in an escalating dose of 2000-10,000 units (U) daily in 60 patients with cancer-related anaemia (CRA). A positive response, defined as an increase in haemoglobin more than 2 g/dl and independence of blood transfusions was observed in 23 of 48 evaluable patients (48%) within a median of 8 wk. In detail, rhEPO corrected anaemia in 11 of 14 patients (79%) with malignant lymphoma, in 8 of 15 patients (53%) with multiple myeloma and in 4 of 10 patients (40%) with a solid tumour. The median dose of rhEPO in successful cases was 5000 U daily. Four patients with agnogenic myeloid metaplasia and 5 with myelodysplastic disorder failed to respond to rhEPO. No patient had any severe side effects. Pretreatment serum erythropoietin levels appeared to be a weak predictor for response to rhEPO treatment. In conclusion, rhEPO seems to be safe and effective in correcting CRA in certain groups of patients.

Topics: Adolescent; Adult; Aged; Anemia; Blood Transfusion; Erythropoietin; Female; Ferritins; Hematocrit; Hemoglobins; Humans; Injections, Subcutaneous; Iron; Lymphoma; Male; Middle Aged; Multiple Myeloma; Myelodysplastic Syndromes; Neoplasms; Primary Myelofibrosis; Recombinant Proteins; Reticulocyte Count; Transferrin

Untreated anemia is common in cancer patients. Previous studies have demonstrated that both the existence of cancer and treatment with chemotherapy can suppress the normal endogenous erythropoietic response to anemia, making some cancer patients transfusion cadidates. In placebo-controlled phase III studies, administration of recombinant human erythropoietin (epoetin alfa) increased hemoglobin (Hb) levels and decreased transfusion requirements in patients undergoing cancer chemotherapy. In these studies, an increase in self-perceived energy level, functional status, and overall quality of life (QOL) was noted in the subset of patients in whom hematocrit levels increased by > or = 6%. To examine more closely the relationship between epoetin alfa therapy and QOL issues in patients undergoing chemotherapy, we conducted an open-label phase IV study involving 2,030 patients treated at 570 community cancer centers in the United States. Patients initially received epoetin alfa 150 U/kg subcutaneously (s.c.) three times per week for 4 months; if response was judged inadequate, the dosage was increased after 8 weeks to 300 U/kg s.c. three times per week. Hb levels and transfusion requirements were monitored monthly. Before and after the study, each patient completed a linear analog self-assessment scale designed to measure energy level, daily activity, and overall QOL. During epoetin alfa therapy, there was a progressive and significant increase (P < .001) in Hb concentrations. Significantly fewer (P < .001) patients were transfused and fewer transfusions were administered per patient per month after the first month of epoetin alfa therapy. Fifty-eight percent of the patients who required a transfusion during the first month of epoetin alfa therapy did not require a transfusion during the subsequent 3 months of the study. The entire patient population demonstrated a significant increase in mean scores for energy level, daily activity, and overall QOL. The magnitude of the increase in these scores correlated with the magnitude of the increase in Hb concentration. Statistically significant improvement in energy scores, daily activity, and overall QOL (P < .05) were observed, regardless of tumor response. These observations require confirmation on placebo-controlled trials, but the implications for oncology practice are important. They suggest that in cancer patients undergoing chemotherapy, the tradition of leaving anemia untreated may compromise patients' ability t

Topics: Administration, Cutaneous; Anemia; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Neoplasms; Quality of Life; Recombinant Proteins

Current evidence suggests that epoetin alpha administration is well tolerated and effective in the management of anemia of cancer and cancer chemotherapy. An open-label, multinational, non-comparative study was conducted in 215 cancer patients with anemia secondary to chemotherapy with platinum- or non-platinum-based combinations. Epoetin alpha was administered s.c. (150 IU/kg three times/week) for a planned period of 16 weeks. The response rate of epoetin alpha, defined as an increase in hemoglobin level of 2 g/dl or more from baseline, was 67%. The rate of response was not related to the chemotherapy regimen administered (platinum or non-platinum based). The percentage of patients transfused and the transfusion rate during epoetin alpha treatment were reduced. Transfusional need was eliminated in 64 (75%) of the 85 patients transfused before the study start, after 1 month of therapy. Quality of life, assessed using a visual analog scale, improved markedly in patients who experienced a hematological response. These patients also experienced a statistically significant (p < 0.0001) improvement in mean WHO performance score. These findings indicate that epoetin alpha is a well tolerated and effective agent which increases hemoglobin concentration and reduces transfusion requirements in anemic cancer patients receiving chemotherapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Carboplatin; Cisplatin; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins

Patients undergoing cancer surgery frequently require blood, and the transfusion of allogeneic blood in these patients has been controversially linked to an increased risk of tumor recurrence. This patient population may therefore benefit from preoperative autologous blood donation (ABD) with or without epoetin alfa therapy, although the precise impact of autologous blood transfusion has not been fully explored. In some trials, preoperative ABD reduced allogeneic blood exposure by 50% in patients undergoing surgery for cancer resection, while, in another study, perioperative treatment with epoetin alfa significantly increased hematocrit (Hct) levels preoperatively and led to a reduction in postoperative allogeneic blood exposure. A combination of epoetin alfa and preoperative ABD seems a reasonable approach to reducing allogeneic blood exposure in patients undergoing cancer surgery.

Topics: Anemia; Blood Transfusion; Blood Transfusion, Autologous; Colorectal Neoplasms; Disease-Free Survival; Epoetin Alfa; Erythropoiesis; Erythropoietin; Gastrointestinal Neoplasms; Humans; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasms; Premedication; Prospective Studies; Recombinant Proteins; Survival Rate; Transfusion Reaction; Treatment Outcome

Although tissue hypoxia is the major stimulus for erythropoietin (EPO) production, serum EPO (sEPO) levels at any given Hb in iron-deficiency anaemia are relatively higher than in other anaemias. Iron chelators stimulate erythropoiesis in anaemia of chronic disease via unknown mechanisms. A recent study suggested that deferoxamine (DFO) regulates steady-state EPO RNA. Here we report that altered intracellular iron balance regulates EPO production both in vitro and in two unique clinical trials. In vitro, both iron chelation with DFO and blockade of Tf-mediated iron uptake with anti-Tf receptor antibody 42/6, stimulated EPO production in serum-deprived hepatoma cells. Conversely, iron repletion by haemin, inhibited EPO production in these cells. In clinical studies, sEPO levels rose in adult volunteers treated with DFO coupled to hydroxyethyl starch (HES-DFO) and in patients with advanced malignancy treated with anti-Tf receptor antibody 42/6, in a time- and dose-dependent manner. These studies indicate intracellular iron balance regulates EPO production in humans.

Topics: Adult; Antibodies, Monoclonal; Blood Cell Count; Carcinoma, Hepatocellular; Cell Hypoxia; Deferoxamine; Dose-Response Relationship, Drug; Double-Blind Method; Erythropoietin; Ferritins; Humans; Iron; Iron Deficiencies; Liver Neoplasms; Male; Neoplasms; Receptors, Transferrin; Tumor Cells, Cultured

A trial to determine the usefulness of recombinant human erythropoietin (rhEpo) as a mobilizing cytokine for patients with previously treated relapsed malignancies was performed. An initial peripheral stem cell apheresis collection was conducted during steady-state hematopoiesis for each patient to provide baseline data. rhEpo, 200 U/kg/day, was administered subcutaneously until the last apheresis procedure was completed. Immediately after the fourth daily dose of Epo, apheresis procedures were resumed and continued beyond five collections, when necessary, to accrue a total of 6.5 x 10(8) mononuclear cells (MNCs)/kg. Eight female and four male patients (median age = 44 years) were evaluated. Five to 14 (median = 8) apheresis procedures were performed for each patient. Toxicity attributable to Epo administration was negligible. Mobilization effects, as determined by an increase in the number of colony-forming units granulocyte/macrophage (CFU-GM) and burst-forming units-erythroid (BFU-E) in the apheresis products after Epo administration, were observed in all patients. Nine patients received high-dose chemotherapy and Epo-mobilized peripheral stem cell transplantation (PSCT). Beginning the day of the transplant, GM-CSF was administered until neutrophil recovery was satisfactory. The median time to recover 0.5 x 10(9)/L granulocytes was 16 days after PSCT. Epo appears to have mobilization properties. Further studies are needed to determine the clinical usefulness of Epo as a mobilizing cytokine. The addition of Epo to other mobilizing cytokines may provide increased effectiveness without adding toxicity.

Topics: Adult; Aged; Cells, Cultured; Combined Modality Therapy; Erythropoietin; Female; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Immunotherapy, Adoptive; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasms; Recombinant Proteins

Topics: Anemia; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Ninety one patients between the ages of 17 and 58 years undergoing histocompatible allogeneic transplants from sibling donors were entered into a double-blind randomised trial to evaluate the effect of human erythropoietin (rhu EPO) at a dose of 300 units per kg/day given thrice weekly by intravenous injection on erythropoiesis and on erythrocyte and platelet transfusion requirements. Dose was ceased when the haemoglobin exceeded 12g/dL and recommenced if the haemoglobin fell below 12 g/dL, at 150 units/kg/day. If the haemoglobin exceeded 12 g/dL on a further occasion, the dose of rhu EPO was not given. Patients received two units of erythrocytes when the haemoglobin dropped below 8.5g/dL and received platelet transfusions when the count dropped below 20 x 10(9)/L. Univariate analysis revealed a significantly higher reticulocyte count, haemoglobin concentration and bone marrow erythropoiesis after day 14 in the group receiving rhu EPO but this was not reflected in decreased erythrocyte transfusion (7 +/- 5 in controls versus 6 +/- 5 in rhu EPO group) or in platelet transfusions (11 +/- 7 in controls versus 11 +/- 9 in rhu EPO group). Hospitalisation in each group was the same (29 +/- 8 in the control group and 28 +/- 8 in the rhu EPO group). However, in the multivariate analysis, the administration of rhu EPO was associated with an 18% reduction in erythrocyte transfusion requirement when other variables were taken into account. No side-effects due to rhu EPO were detected in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Bone Marrow Examination; Bone Marrow Transplantation; Double-Blind Method; Erythrocyte Transfusion; Erythropoietin; Female; Graft vs Host Disease; Hemoglobins; HLA Antigens; Humans; Male; Middle Aged; Multivariate Analysis; Neoplasms; Nuclear Family; Platelet Transfusion; Prospective Studies

Chemotherapy-induced anemia in children with cancer is usually of acute onset. To investigate an alternate treatment to transfusion (Tx), we undertook a phase I-II clinical trial of daily administrations of recombinant erythropoietin (rHuEPO). Patients with a hemoglobin (Hgb) value < 75 g/l were treated for 14 days in cohorts of 3 at escalating daily doses of 25, 50, 70, 80, 90, and 100 U/kg respectively. The maximum-tolerated dose was not encountered. Of 18 courses given to 15 children aged 0.5-18 years, 7 (39%) were associated with increased or stable Hgb levels (courses without Tx), while 11 (61%) were terminated by a Tx, without evidence of a dose-response relationship. Changes in mean Hgb levels and absolute reticulocyte counts were paralleled by those of mean white blood cell, platelet, and absolute neutrophil counts during the first 7 days and when the end-points of the study were reached. Numbers of circulating burst-forming units-erythroid remained low throughout courses without Tx. No cumulative increase of serially determined serum EPO levels was observed and serum ferritin levels were elevated in both groups of courses. We conclude that daily administration of rHuEPO were safe but ineffective in our trial. Recovery of chemotherapy-induced myelosuppression appeared to be the rate-limiting factor for the outcome, without evidence of an enhanced stimulation of erythropoiesis. The lack of a proliferative response of specific progenitor cells suggested a mechanism of transient primary resistance to rHuEPO.

Topics: Acute Disease; Adolescent; Anemia; Antineoplastic Agents; Child; Child, Preschool; Erythropoietin; Female; Humans; Infant; Infant, Newborn; Iron; Male; Neoplasms; Recombinant Proteins

Chronic anemia is a common complication in patients with cancer, especially in those with advanced disease or who are under intensive chemotherapy. Because homologous blood transfusions involve some hazards, the safety and efficacy of recombinant human erythropoietin (r-HuEPO) in the treatment of anemic patients with cancer with and without concomitant chemotherapy were studied.. One-hundred two cancer patients with hemoglobin less than 11 g/dl, ferritin greater than 30 micrograms/l, and creatinine < 220 mumol/l were enrolled in the study, 94 were eligible for efficacy evaluation. Sixty-eight patients received chemotherapy (CT group) and 26 had no cytotoxic cancer treatment (NT group). Recombinant human erythropoietin was administered subcutaneously at a dose of 150 U/kg three times per week for 6 weeks; in nonresponders the dose was doubled for the subsequent 6 weeks. Response was defined as the achievement of a hemoglobin increase of 2g/dl. Clinical and laboratory parameters, including serum erythropoietin (EPO) levels, performance status, and quality of life, were investigated at baseline and monitored at regular intervals thereafter.. Response was achieved by 52% and 62% of CT and NT patients, respectively. The highest response rates were observed in patients with lung cancer or with a histology of squamous cell carcinoma (both 80%). In responding patients, the symptoms of anemia subsided. They no longer needed blood transfusions after 4 weeks of therapy; and both their performance status and quality of life improved significantly. The NT patients achieved slightly more favorable results on lower weekly doses: 450 U/kg/week in NT versus 570 U/kg/week in CT patients. Serum EPO levels were higher in nonresponders at baseline and further increased during the course of treatment. Recombinant human erythropoietin was well tolerated by all patients.. This multicenter study in a large patient collective shows that r-HuEPO treatment represents a safe and effective means to increase the red cell mass and eliminate the need for blood transfusions in approximately 50% of the patients with chronic anemia of cancer. Responding patients not only have increased levels of hemoglobin, but their performance status also improves significantly, and they enjoy a significantly enhanced quality of life.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Blood Transfusion; Carcinoma, Squamous Cell; Chronic Disease; Creatinine; Erythrocyte Volume; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Injections, Subcutaneous; Lung Neoplasms; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins; Remission Induction

Topics: Anemia; Antineoplastic Agents; China; Erythropoietin; Hemoglobins; Humans; Injections, Subcutaneous; Iron; Neoplasms; Recombinant Proteins

Topics: Adult; Aged; Antibodies, Monoclonal; Antigens, CD; Antigens, CD34; Blood Cells; Colony-Forming Units Assay; Erythropoietin; Female; Flow Cytometry; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Male; Middle Aged; Neoplasms

Chronic anemia of cancer can be corrected in approximately 50% of the cases by treatment with recombinant human erythropoietin (rHuEPO). Early prediction of responsiveness would avoid the emotional and financial burden of ineffective medical intervention. Eighty patients with chronic anemia of cancer undergoing treatment with rHuEPO (150 U/kg, 3 times per week by subcutaneous injection; after 6 weeks without response, 300 U/kg) participated in this study. Response was defined as a gain of at least 2 g/dL hemoglobin (Hb) within 12 weeks. Multivariate discriminant analysis and logistic regression analysis of response were performed on routine blood tests; serum levels of EPO, iron, ferritin, transferrin, and its receptor; World Health Organization (WHO) performance status; various cytokines; neopterin; stem cell factor; C-reactive protein; and alpha 1-antitrypsin. At baseline, none of these factors showed sufficient prognostic power. The following predictive algorithm was developed: (1) If after 2 weeks of therapy both the serum EPO level is > or = 100 mU/mL and Hb concentration has not increased by at least 0.5 g/dL, unresponsiveness of the patient is very likely (predictive power, 93%); otherwise, response may be predicted with an accuracy of 80%. (2) If both the serum level of EPO is less than 100 mU/mL and Hb concentration has increased by > or = 0.5 g/dL, response is highly probable (predictive power, 95%). (3) Alternatively, a serum ferritin level of > or = 400 ng/mL after 2 weeks of rHuEPO therapy strongly indicates unresponsiveness (predictive power, 88%), whereas a level less than 400 ng/mL suggests response in 3 of 4 patients.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Anemia; Discriminant Analysis; Erythropoietin; Female; Ferritins; Humans; Male; Middle Aged; Neoplasms; Predictive Value of Tests; Prognosis; Recombinant Proteins; Regression Analysis; Survival Analysis; Time Factors

Patients with solid tumours undergoing high-dose chemotherapy with autologous bone marrow transplantation use an average of 10 units of packed red blood cells (PRBC) while awaiting haemopoietic reconstitution. They are also known to have inappropriately low endogenous erythropoietin levels for their degree of anaemia. This pilot study was designed to determine the effects of recombinant human erythropoietin (rHuEPO) on erythroid recovery and PRBC transfusion requirements. Ten patients received high-dose chemotherapy (days -7 to -3), bone marrow reinfusion (day 0), and then rHuEPO (day 1 onward). RHuEPO (200 units/kg intravenous bolus daily), along with iron supplementation, was administered for 28 d or until a haematocrit (Hct) of 35% (independent of transfusions) was reached, whichever occurred first. PRBCs were routinely given for Hct < or = 25% and platelets for counts < 20,000/microliters. Eight (80%) patients developed a brisk reticulocytosis (median peak reticulocyte count 0.32 x 10(9)/l) and a haematocrit > or = 30% independent of red blood cell transfusions within 32 d of receiving marrow, as compared to 20/37 (54%) similarly treated controls. An unexpected finding was the more rapid engraftment in myeloid and platelet lineages in a subset of rHuEPO-treated patients. Quick return of red blood cells (17 v 33 d) (P = 0.0001), platelets (14 v 19 d) (P = 0.04), and neutrophils (13 v 25 d) (P = 0.01) (with circulating myeloblasts and early myeloid forms) characterized recovery from an ifosfamide-based intensification with rHuEPO support. Similar trilineage enhancement of haemopoiesis did not occur with the possibly more myeloablative cyclophosphamide-based regimens. Despite the enhancement by rHuEPO on reticulocytosis, there was no significant decrease in PRBC transfusion requirements. RHuEPO proved to be a well-tolerated agent in enhancing reticulocytosis following high-dose chemotherapy. Further study to elucidate the activity of erythropoietin on both erythroid and non-erythroid growth and maturation appears warranted.

Topics: Adult; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Component Transfusion; Bone Marrow Transplantation; Combined Modality Therapy; Erythropoietin; Female; Humans; Iron; Male; Middle Aged; Neoplasms; Pilot Projects; Recombinant Proteins; Reticulocyte Count

Topics: Anemia; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Improvements in quality of life after treatment with recombinant human erythropoietin (rHuEPO) often have been reported in patients with end-stage renal disease. In patients with chronic anemia of cancer, comparatively few systemic investigations have been performed.. Various aspects of quality of life were self-reported on linear analogue scales of a slightly modified questionnaire that was first developed to assess toxicity of chemotherapy in patients with breast cancer. Thirty-four patients with chronic anemia of cancer completed 10 items (feelings of well-being, mood, level of activity, pain, nausea, appetite, physical ability, social activities, anxiety, and helpfulness of therapy) before and after 8 and 12 weeks of rHuEPO therapy.. Patients with response to the therapy significantly improved after 8 weeks of treatment in some items and after 12 weeks in all items. Patients with no response also had some improvement after 12 weeks of therapy. Hemoglobin levels correlated strongly with mood and appetite. World Health Organization (WHO) performance status improved significantly in patients with response but tended to diminish in those without. Median survival was 4.1 months in patients with no response and 12.0 months in those with response. After 12 weeks of therapy, the scores of the items "physical ability" and "social activities" proved to be significant prognostic factors, which surpassed the prognostic power of the WHO performance status.. The results of rHuEPO therapy in chronic anemia of cancer are far more than cosmetics of laboratory values. They enable the patients with response to lead a physically and socially more active life with less anxiety, brighter moods, and an increased general feeling of well-being.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins; Surveys and Questionnaires

Anemia associated with advanced cancer is common. Contributing factors include the anemia of chronic disease, chemotherapy, radiation therapy, and bone marrow invasion with tumor. Based on the observation that endogenous erythropoietin (EPO) levels in anemic patients with cancer are inadequate for the degree of anemia, three randomized double-blind, placebo-controlled trials of recombinant human erythropoietin (rHuEPO) treatment in anemic patients with cancer were performed in patients (1) not receiving concomitant chemotherapy (NO CTX), (2) receiving myelosuppressive chemotherapy that did not include cisplatin (CTX-NO PLAT), and (3) receiving myelosuppressive cisplatin-containing chemotherapy (CTX-PLAT). In the NO CTX trial, patients were treated with rHuEPO 100 U/kg or placebo subcutaneously (SQ) three times per week for up to 8 weeks. In the CTX trials, patients were treated with rHuEPO 150 U/kg or placebo SQ three times per week for 12 weeks. Four hundred thirteen patients were enrolled (124, NO CTX; 157, CTX-NO PLAT; and 132, CTX-PLAT). In all three trials, patients receiving rHuEPO had a significantly (P < .004) greater increase in hematocrit (HCT) than placebo-treated patients. In the two CTX trials combined, rHuEPO-treated patients also had a significantly (P < or = .009) lower transfusion requirement than placebo-treated patients after the first month of therapy. Quality of life improved significantly (P < .05) in responding (> or = 6%-point HCT increase without transfusion) rHuEPO-treated patients compared with placebo-treated patients. Overall, no adverse events occurred more frequently in rHuEPO-treated patients compared with placebo-treated patients. Following completion of the double-blind phase, patients received rHuEPO on an open-label basis as needed for correction of anemia with the dose titrated to a maximum of 900 U/kg/wk. During total rHuEPO exposure (either started at the beginning of double-blind therapy for patients initially randomized to rHuEPO or at the beginning of open-label therapy for patients initially randomized to placebo; 363 treated/347 evaluable for efficacy), 40.0%, 56.1%, and 58.3% of the NO-CTX, CTX-NO PLAT, and CTX-PLAT patients, respectively, responded to rHuEPO therapy with an increase of HCT > or = 6% unrelated to transfusion.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Cisplatin; Double-Blind Method; Erythropoietin; Female; Hematocrit; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins

The hemoglobin (Hgb) level of patients during radiation therapy is associated with both survival and local tumor control in several organ sites. This clinical trial tested whether administering recombinant human erythropoietin (r-HuEPO) to cancer patients would increase their Hgb level during the course of radiation therapy without adverse effects.. The 40 participating patients had a Hgb value < 13.5 g/dL and a malignant tumor located above the diaphragm without evidence of distant metastasis for which they were scheduled to undergo a 5-8 week course of daily radiation therapy. All 40 patients were given oral ferrous sulfate throughout their radiation therapy course. Half the patients also received 150-300 mg/kg of r-HuEPO subcutaneously three times per week starting 0-10 days prior to the first dose of radiation.. The r-HuEPO and control groups did not differ significantly in patient age, gender, tumor type, initial hemoglobin, erythropoietin, or iron bioavailability. The Hgb level increased more than 6% during radiation therapy in all 20 of the r-HuEPO patients but in only 2/20 of the control patients (p < 0.001). The Hgb rose from a mean +/- standard deviation of 11.9 +/- 1.3 g/dL to > 14 g/dL during radiation therapy in 80% of the r-HuEPO group compared to in 5% of the control group (p < 0.001). The mean +/- s.d. change in Hgb concentration during radiation therapy was 27 +/- 15% (an average rise of 5% per week) in the r-HuEPO group and 0 +/- 6% in the control group (p < 0.001). r-HuEPO had no significant measurable effect on blood pressure, white blood cell, neutrophil or platelet count, or liver or renal function. The only reported adverse effect of r-HuEPO administration was an asymptomatic skin rash in one patient.. r-HuEPO with ferrous sulfate significantly increased the Hgb level in cancer patients without interfering with their course of radiation therapy, whereas ferrous sulfate alone did not. r-HuEPO appears to be a safe and effective means of increasing red cell mass during radiation therapy.

Topics: Erythropoietin; Female; Ferrous Compounds; Hemoglobins; Humans; Leukocyte Count; Male; Middle Aged; Neoplasms; Platelet Count; Radiotherapy; Recombinant Proteins

Topics: Adult; Aged; Anemia; Cisplatin; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins

Topics: Bone Marrow Transplantation; Drug Therapy, Combination; Erythropoiesis; Erythropoietin; Granulocyte-Macrophage Colony-Stimulating Factor; Granulocytes; Hematopoiesis; Humans; Megakaryocytes; Neoplasms; Pilot Projects; Recombinant Proteins

Topics: Aged; Anemia; Antineoplastic Agents; Blood Transfusion; Bone Marrow; Cisplatin; Double-Blind Method; Erythropoietin; Female; Hematocrit; Humans; Male; Middle Aged; Neoplasm Invasiveness; Neoplasms; Quality of Life; Recombinant Proteins

The toxicities and possible utility of the combination of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and recombinant human erythropoietin (rHuEPO) given after autologous BMT were evaluated in this pilot trial. Eighteen patients received the combination and were compared with six concurrent control and 65 historical control patients treated with rhGM-CSF alone. Patients treated with the combination tended to have more rapid recovery to an absolute neutrophil count of 500 x 10(6)/l (median = 12.5 vs 18 days for concurrent and 19 days for historical control patients). There was no apparent impact on red cell transfusion requirements, platelet recovery or duration of hospitalization. Patients treated in the current study with rhGM-CSF plus either rHuEPO or with placebo had a higher incidence of rash than seen in our historical experience using rhGM-CSF. This difference may reflect changes in the source of rhGM-CSF or in the infusion schedule. Erythropoietin can be combined safely with rhGM-CSF after autologous transplantation. Larger controlled trials will be necessary to detect possible therapeutic effects.

Topics: Adolescent; Adult; Bone Marrow Transplantation; Child; Child, Preschool; Double-Blind Method; Drug Therapy, Combination; Erythropoietin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Male; Middle Aged; Neoplasms; Transplantation, Autologous

Patients with advanced cancer frequently experience clinically significant anemia, which is often exacerbated by myelosuppressive chemotherapy. Consistent with the anemia of chronic disease, studies have documented serum erythropoietin levels that are inappropriately low for the degree of anemia in cancer patients. Myelosuppressive chemotherapy impairs erythropoiesis, which may not fully recover between treatment cycles. Recombinant human erythropoietin (rHuEPO) has been used safely and effectively to treat anemia in AIDS patients receiving zidovudine (AZT) and in patients with chronic renal failure.. This study was designed to evaluate the clinical role of rHuEPO in reducing symptomatic anemia in patients with advanced cancer who were receiving myelosuppressive chemotherapy (excluding cisplatin).. We studied 153 anemic cancer patients receiving cyclic combination chemotherapy in a prospective multicenter, double-blind, placebo-controlled trial. The patients were randomly assigned to receive either rHuEPO (150 U/kg) or placebo subcutaneously three times a week for a maximum of 12 weeks or until the hematocrit level increased to 38%-40%. If the hematocrit reached this target level before 12 weeks, the rHuEPO dose could be reduced to maintain the hematocrit at that level for the duration of the study. Response to rHuEPO therapy was assessed by measuring changes in hematocrit level, transfusion requirements, and quality of life. Quality-of-life assessment was based on patients' responses to questionnaires before and after the courses of therapy.. The increase in hematocrit in the rHuEPO-treated group compared with hematocrit in the placebo-treated group was statistically significant (P = .0001) as measured by percentage point of change from baseline to final evaluation, by an increase in hematocrit level of six percentage points or more unrelated to transfusion, and by a rise in hematocrit level to 38% or more unrelated to transfusion. There was a trend toward the reduction in mean units of blood transfused per patient during months 2 and 3 of therapy combined in rHuEPO-treated patients compared with placebo-treated patients (0.91 U versus 1.65 U; P = .056). In addition, rHuEPO-treated patients experienced a statistically significant improvement in energy level and ability to perform daily activities (P < or = .05). The two treatment groups showed no statistically significant differences in toxic effects except for increased incidence of diaphoresis (P < .05) and diarrhea (P = .05) in the rHuEPO-treated group.. We conclude that rHuEPO is safe and effective for reversing anemia related to advanced cancer or to chemotherapy for cancer.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Double-Blind Method; Erythropoietin; Female; Hematocrit; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins

Advanced cancer is often accompanied by anaemia, which may worsen with concomitant administration of chemotherapy. Serum erythropoietin (EPO) concentrations are lower in cancer patients than in patients with iron deficiency, suggesting that the anaemia observed in cancer patients is at least partially due to a relative deficiency of EPO. Consequently, we studied the effects of recombinant human erythropoietin (r-HuEPO) therapy in three populations of anaemic cancer patients: patients not receiving concomitant chemotherapy or radiotherapy; patients receiving cyclic, non-cisplatin-containing chemotherapy, and patients receiving cyclic cisplatin-containing chemotherapy. Therapy with r-HuEPO was well tolerated; it increased haematocrit levels and corrected anaemia, irrespective of concomitant chemotherapy or the type of chemotherapy administered. A dose of 150 U/kg r-HuEPO given subcutaneously 3 times weekly decreased transfusion requirements after the 1st month of therapy; improved functional capacity was noted in patients who achieved a significant increase in haematocrit in response to r-HuEPO therapy.

Topics: Anemia; Blood Transfusion; Bone Marrow; Cisplatin; Erythropoietin; Female; Hematocrit; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins

Topics: Anemia; Cisplatin; Clinical Trials as Topic; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

This clinical trial was performed to study the effects of intravenously (IV) administered recombinant human (rh) erythropoietin (EPO) at escalating doses (150, 300, and 450 U/kg, administered as an IV bolus injection, twice weekly, for 6, 4, and 4 weeks, respectively) in five patients with low-grade non-Hodgkin's lymphoma (Ig NHL) and bone marrow involvement and one patient with multiple myeloma (MM). All patients were anemic due to underlying disease. None of the patients had a history of bleeding, hemolysis, renal insufficiency, or other disorders causing anemia in addition to bone marrow infiltrating malignancy. Endogenous EPO serum levels were significantly increased in all patients (74 to 202 mU/mL). Five patients (one MM, four small-cell lymphocytic [SCLC] NHL) showed a dramatic increase of hemoglobin (Hb), hematocrit (Hk) and RBC count becoming obvious on the second EPO dose level. Initial ferritin serum values, which were high mostly due to polytransfusion, were significantly reduced in responding patients. Erythropoiesis of one patient with extensive follicular mixed (fm) NHL did not respond to EPO treatment. Platelet (PLT) count increase (greater than 75% above starting levels) during and following EPO therapy was observed in one patient with MM. Adverse events due to EPO therapy have not been recorded. These findings point out a previously unrecognized capacity of EPO given at pharmacologic doses to stimulate erythropoiesis in patients with anemia due to bone marrow infiltration by neoplastic lymphocytes in spite of enhanced endogenous EPO expression.

Topics: Aged; Anemia; Blood Coagulation; Bone Marrow; Clinical Trials as Topic; Erythropoiesis; Erythropoietin; Female; Ferritins; Hematopoiesis; Humans; Kinetics; Male; Middle Aged; Neoplasms; Tumor Necrosis Factor-alpha

Topics: Animals; Clinical Trials as Topic; Erythropoietin; Growth Substances; Humans; Neoplasms

Topics: Anemia; Arteriovenous Shunt, Surgical; Erythropoietin; Humans; Hypertension; Kidney Failure, Chronic; Multicenter Studies as Topic; Neoplasms; Renal Dialysis; Seizures; Thrombocytosis; Thrombosis

The prespecified on-treatment analysis of ASCEND-ND (NCT02876835) raised concerns about a higher relative risk of cancer-related adverse events (AEs) with daprodustat vs darbepoetin in patients with anaemia of CKD. This concern was not observed in dialysis patients in ASCEND-D (NCT02879305).. ASCEND-ND randomized 3872 patients to daprodustat or darbepoetin. ASCEND-D randomized 2964 patients to daprodustat or conventional erythropoiesis-stimulating agents (ESAs). In both studies ESA comparators used different dosing intervals (3/week, 1/week, every 2 or every 4 weeks). The prespecified on-treatment approach examined relative risks for cancer AEs up to the last dose date + 1 day. In these analyses, owing to different dosing intervals between arms, Cox models were used to estimate the daprodustat effect by various follow-up periods (censoring at last dose date, last dose date + dosing intervals, or end of study).. In ASCEND-ND, the safety of daprodustat vs darbepoetin on cancer-related AEs depended on the duration of follow-up after last dose date: hazard ratio (HR) 1.04 [95% confidence interval (CI) 0.77, 1.40] at end of study [HR 1.12 (95% CI 0.81, 1.56) for last dose date + dosing interval; HR 1.50 (95% CI 1.04, 2.15) for last dose date + 1 day]. In ASCEND-D, no excess risk of cancer-related AEs was observed with any model examined.. Prespecified on-treatment analyses for cancer-related AEs appeared to result in biased risk estimates in ASCEND-ND by preferentially under-counting events from patients assigned to darbepoetin. Analyses accounting for longer darbepoetin dosing intervals, or extending follow-up, resulted in attenuation of effect estimates towards neutrality, similar to ASCEND-D, where ESA comparator dosing intervals are closer to daprodustat.. The ASCEND-ND trial is registered with ClinicalTrials.gov (NCT02876835); the ASCEND-D trial is registered with ClinicalTrials.gov (NCT02879305).

Topics: Darbepoetin alfa; Erythropoiesis; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Renal Dialysis; Renal Insufficiency, Chronic

化疗相关性贫血是肿瘤患者常见的并发症，总体发病率高，但治疗率不理想，是导致患者预后不良的重要危险因素。当前治疗手段有限，且存在血源紧张、红细胞生成刺激剂和铁剂使用不规范、不良反应多、治疗费用高等各种不足。临床工作中需要根据指南评估病情和制定个体化治疗方案，合理有效地早期干预，积极开发早期监测手段及新型药物，以期提高患者生活质量，改善临床预后，减轻疾病负担。.

Topics: Anemia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Erythropoietin (EPO) suppresses drug-induced apoptosis in EPO-receptor-positive leukemia cells and allows cells to persist after drug treatment by promoting cellular senescence. Importantly a small proportion of senescent cells can re-enter the cell cycle and resume proliferation after drug treatment, resulting in disease recurrence/persistence. Using a single-cell assay to track individual cells that exit a drug-induced senescence-like state, we show that cells exhibit asynchronous exit from a senescent-like state, and display different rates of proliferation. Escaped cells retain sensitivity to drug treatment, but display inter-clonal variability. We also find heterogeneity in gene expression with some of the escaped clones retaining senescence-associated gene expression. Senescent leukemia cells exhibit changes in gene expression that affect metabolism and senescence-associated secretory phenotype (SASP)-related genes. Herein, we generate a senescence gene signature and show that this signature is a prognostic marker of worse overall survival in AML and multiple other cancers. A portion of senescent leukemia cells depend on lysosome activity; chloroquine, an inhibitor of lysosome activity, promotes senolysis of some senescent leukemia cells. Our study indicates that the serious risks associated with the use of erythropoietin-stimulating agents (ESAs) in anemic cancer patients may be attributed to their ability to promote drug-tolerant cancer cells through the senescence program.

Topics: Apoptosis; Cellular Senescence; Erythropoietin; Humans; Leukemia; Neoplasms

Few effective therapies are available to treat patients with relapsed/refractory myelodysplastic neoplasms (MDS). Luspatercept was shown to display good efficacy in a phase 3 clinical trial for lower-risk MDS (LR-MDS) patients, yet real-world data are limited, especially in China. Therefore, data from patients diagnosed as having MDS with low blasts and SF3B1 mutation (MDS-SF3B1) and MDS with SF3B1 mutation and thrombocytosis were retrospectively analyzed. Of the 23 enrolled patients, 17 (73.9%) were males (median age 67 years: range 29 to 80 years). Previously, a total of 22 (95.7%) patients had received recombinant human erythropoietin (rhEPO), 9 (39.1%) roxadustat, 7 (30.4%) lenalidomide and 3 (13.0%) hypomethylating agents (HMA). The median treatment time was 22.9 weeks (9.0-32.4). At week 12, 60.9% (14/23) of the patients achieved a hematologic improvement-erythroid (HI-E) response. Red blood cell transfusion independence (RBC-TI) for ≥ 8 weeks was found in 57.1% (8/14) of transfusion-dependent patients. The median hemoglobin concentration was 84 g/L, and patients had significantly higher hemoglobin concentrations after 12 weeks of treatment (P < 0.001). It is noteworthy that responders had a greater reduction in serum ferritin (P = 0.021). Those with serum EPO < 500 IU/L at baseline tended to have a higher HI-E rate (P = 0.081), but only patients in non-transfusion and low transfusion burden (LTB) subgroups had statistical differences (P = 0.024). The most commonly occurring adverse events were blood bilirubin increase (17.4%), fatigue (13.0%) and dizziness (13.0%). Luspatercept was effective and tolerated well in refractory LR-MDS-SF3B1 patients. In particular, baseline non-transfusion and LTB patients exhibited a greater response rate to treatment.

Topics: Adult; Aged; Aged, 80 and over; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Neoplasms; Recombinant Proteins; Retrospective Studies

Anemia is a common condition, but its causes are often unclear, especially in elderly adults. Erythropoietin (EPO) levels are known to be elevated in myelodysplastic syndrome and hematologic malignancies, but decreased in chronic benign anemia. This study aimed to investigate whether EPO levels could be used to identify underlying bone marrow diseases including malignancies, among elderly anemic patients with unclear etiology. This single centered retrospective study included patients presented with isolated anemia and had their EPO levels measured at their first visit. Patients were divided into two groups: bone marrow disease and benign etiologic anemia, based on observation and bone marrow test results. Out of 1180 patients reviewed, 81 patients with anemia of unclear etiology were identified, including 67 with benign anemia and 14 with bone marrow disease. Statistically significant difference in EPO levels between these two groups (P < 0.001) were observed. The receiver operating characteristic curve analysis showed that an EPO cut-off value of 36.4 mU/mL had a sensitivity and specificity of 92.8% and 94.0% for detecting underlying bone marrow disease, respectively. We suggest measuring serum EPO levels can aid in the early detection of benign anemia from bone marrow disease, including malignancies, with high sensitivity and specificity.

Topics: Adult; Aged; Anemia; Erythropoietin; Humans; Myelodysplastic Syndromes; Neoplasms; Retrospective Studies

Topics: Anemia; Carbon; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Humans; Neoplasms

We found that in regenerative erythropoiesis, the erythroid progenitor landscape is reshaped, and a previously undescribed progenitor population with colony-forming unit-erythroid (CFU-E) activity (stress CFU-E [sCFU-E]) is expanded markedly to restore the erythron. sCFU-E cells are targets of erythropoietin (Epo), and sCFU-E expansion requires signaling from the Epo receptor (EpoR) cytoplasmic tyrosines. Molecularly, Epo promotes sCFU-E expansion via JAK2- and STAT5-dependent expression of IRS2, thus engaging the progrowth signaling from the IGF1 receptor (IGF1R). Inhibition of IGF1R and IRS2 signaling impairs sCFU-E cell growth, whereas exogenous IRS2 expression rescues cell growth in sCFU-E expressing truncated EpoR-lacking cytoplasmic tyrosines. This sCFU-E pathway is the major pathway involved in erythrocytosis driven by the oncogenic JAK2 mutant JAK2(V617F) in myeloproliferative neoplasm. Inability to expand sCFU-E cells by truncated EpoR protects against JAK2(V617F)-driven erythrocytosis. In samples from patients with myeloproliferative neoplasm, the number of sCFU-E-like cells increases, and inhibition of IGR1R and IRS2 signaling blocks Epo-hypersensitive erythroid cell colony formation. In summary, we identified a new stress-specific erythroid progenitor cell population that links regenerative erythropoiesis to pathogenic erythrocytosis.

Topics: Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Humans; Myeloproliferative Disorders; Neoplasms; Polycythemia; Receptor, IGF Type 1; Receptors, Erythropoietin

Risk evaluation and mitigation strategy (REMS) programs are intended to improve safe use of US Food and Drug Administration-approved drugs. However, controversy exists over whether they consistently accomplish this goal.. We aimed to assess how initiation of the erythropoiesis stimulating agents (ESAs) darbepoetin alfa and epoetin alfa changed following implementation and enforcement (following a 1-year post-implementation grace period) of a prominent REMS program warning physicians against use in cancer patients with hemoglobin above 10 g/dL.. Using claims data from a large US commercial insurance company, we conducted interrupted time-series analyses of darbepoetin alfa and epoetin alfa initiation among adult cancer patients in the 12 months before REMS program implementation, after REMS program implementation, and after REMS program enforcement. We also evaluated differences in inappropriate initiation (hemoglobin tests all above 10 g/dL in the prior month) between the periods.. In total, we identified 3456 darbepoetin alfa initiators and 2632 epoetin alfa initiators. Over the study period, the monthly number of initiators per 100,000 patients with cancer fell from 119 to 32 for darbepoetin alfa and from 82 to 34 for epoetin alfa. However, non-significant post-REMS program implementation level and slope changes per 100,000 adult patients with cancer were observed for darbepoetin alfa (level 0.03 [95% confidence interval (CI) -14.98 to 15.05]; slope 1.94 [95% CI -0.22 to 4.10]) and epoetin alfa (level -4.10 [95% CI -16.85 to 8.65]; slope -0.52 [95% CI -2.35 to 1.32]). Non-significant post-REMS program enforcement level and slope changes were also seen for both drugs (darbepoetin alfa level 1.58 [95% CI -0.58 to 3.74, slope -0.28 [95% CI -15.29 to 14.73]; epoetin alfa level 1.58 (95% CI -0.26 to 3.42], slope 5.74 [95% CI -7.01 to 18.49]). Finally, non-significant changes in inappropriate darbepoetin alfa (60% vs. 53% vs. 57%, p = 0.68) and epoetin alfa (53% vs. 53% vs. 46%, p = 0.41) initiation were observed between the three study periods.. REMS program implementation and enforcement were not associated with significant changes in ESA initiation, adding to concerns over the degree to which certain REMS programs enhance patient safety.

Topics: Adult; Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Recombinant Proteins; Risk Evaluation and Mitigation

Evidences show that around 20% of biosimilar or originator erythropoiesis-stimulating agents (ESAs) users are hyporesponsive. Controversial post-marketing data exist on the predictors of ESA hyporesponsiveness. The aim of this study was to identify predictors of ESA hyporesponsiveness in patients with chronic kidney disease (CKD) or cancer in clinical practice.. During the years 2009-2015, a multi-center, population-based, cohort study was conducted using claims databases of Treviso and Caserta Local Health Units (LHUs). All incident ESA users were characterized at baseline and the differences between the baseline hemoglobin (Hb) value, that is the Hb registered within 30 days prior to the first ESA dispensing (index date, ID) and each outcome Hb value (registered between 30 and 180 days after ID) were calculated and defined as delta Hb (ΔHb). Incident ESA users were defined as hyporesponsive if, during follow-up, they registered at least one ΔHb < 0 g/dL. Including all potential predictors of ESA hyporesponsiveness and stratifying by indication for use, univariate and multivariate binary logistic regression models and Receiver Operating Characteristic (ROC) curves were carried out.. In general, 1080 incident ESA users (CKD: 57.0%; cancer: 43.0%) were identified. In CKD, predictors of ESA hyporesponsiveness were C-reactive protein (OR = 1.2, 95% CI: 1.0-1.5; P-value = 0.060) and high levels of baseline Hb (OR = 1.7, 95% CI: 1.2-2.2; P-value< 0,001), the latter being also predictor of ESA hyporesponsiveness in cancer (OR = 1.7, 95% CI: 1.1-2.4; P-value = 0.007). Both in CKD and in cancer, the type of ESA, biosimilar or originator, was not a predictor of ESA hyporesponsiveness. In CKD, concomitant use of iron preparations (OR = 0.3, 95% CI: 0.2-0.7; P-value = 0.002) and of high dosage of angiotensin-converting enzyme inhibitors/angiotensin II-receptor blockers (OR = 0.5, 95% CI: 0.3-0.9; P-value = 0.022) were protective factors against ESA hyporesponsiveness.. The study confirmed traditional potential predictors of hyporesponsiveness to ESA. The use of biosimilar or originator ESA was not a predictor of hyporesponsiveness in an outpatient setting from two large Italian areas. A better knowledge of the predictors of ESA response would allow a better anemia management to improve patients' quality of life.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Cohort Studies; Erythropoiesis; Erythropoietin; Female; Follow-Up Studies; Forecasting; Hematinics; Humans; Italy; Male; Middle Aged; Neoplasms; Population Surveillance; Renal Insufficiency, Chronic; Retrospective Studies

Topics: Cells; Erythropoietin; Hypoxia-Inducible Factor 1; Neoplasms; Nobel Prize; Oxygen; Von Hippel-Lindau Tumor Suppressor Protein

Topics: Anemia; Biomedical Research; Erythrocytes; Erythropoietin; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Neoplasms; Nobel Prize; Oxygen; Transcription, Genetic; United Kingdom; United States

Purpose In March 2007, a US Food and Drug Administration boxed warning was issued for erythropoietin-stimulating agents (ESAs) regarding serious adverse events, such as venous thromboembolism (VTE). We evaluated the US Food and Drug Administration's boxed warning of ESAs used to treat chemotherapy-induced anemia because evidence on the effectiveness of boxed warnings remains inconclusive. Patients and Methods Using 2004 to 2009 SEER-Medicare data, we exploited a natural experiment to examine the effects of ESA boxed warnings on utilization and risk of VTE. The intervention group included Medicare fee-for-services patients diagnosed with colorectal, breast, or lung cancers targeted by this warning and undergoing chemotherapy; the control group included patients with myelodysplastic syndromes not targeted by this warning. The period from January 2004 to September 2006 was used as the prewarning period; the period from April 2007 to September 2009 was used as the postwarning period. The two binary dependent variables included ESA use and hospitalized VTE. Linear probability models with a difference-in-differences specification were used for estimation. Results Our sample consisted of 45,319 unique patients between 2004 and 2009. The trends in ESA use remained similar between the intervention and control groups before the warning, but started declining sharply in the intervention group only after the warning. The trends in hospitalized VTE were relatively stable. Regressions showed that the ESA boxed warning was associated with a 20.2-percentage-point reduction ( P < .001) in the likelihood of ESAs being used to treat cancers targeted by the warning, but not significantly associated with the likelihood of hospitalized VTE. Conclusion Our study showed that the warning was effective in reducing ESA utilization. Future studies should examine other regulatory drug safety actions, such as the Risk Evaluation and Mitigation Strategy initiative, whose effectiveness remains unknown.

Topics: Aged; Aged, 80 and over; Drug Labeling; Drug Utilization; Erythropoietin; Female; Hematinics; Humans; Male; Medicare; Middle Aged; Neoplasms; SEER Program; United States; United States Food and Drug Administration

This is a single-center uncontrolled retrospective study to evaluate the efficacy and safety of the biosimilar epoetin zeta after approval in chemotherapy-induced anemia (CIA).. Patients screened were >18 years old suffering from solid malignancies and CIA with Hg ≤10 or <11 g/dl if symptomatic anemia. Patients had measurable disease by TNM and Eastern Cooperative Oncology Group (ECOG). Patients were treated for at least 12 weeks and the primary endpoint was to determine the incidence of blood transfusions, and secondarily, the overall safety and efficacy defined as ≥1 g/dl rise in Hb concentration or ≥40,000 cells/μl rise in reticulocyte count. Quality of life was assessed with ECOG performance status (PS) and functional assessment of cancer therapy-anemia (FACT-An) score.. 1287 patients with median Hb 9.3 g/dl (range 8.3-10.6) were enrolled and included in the evaluation. Median age was 63 years (range 33-78). 74% of patients were stage III/IV. Patients received epoetin zeta subcutaneously at fixed 40,000-IU once weekly. Blood transfusions were given in 178 patients (13.8%; 95% CI 11.9-15.6%). Appropriate response was observed in 79% patients by week 4, 87% by week 8, and 91% by week 12. A mean Hb increase of 2.5 g/dl was observed by week 12 which correlated with an improvement in PS and Fact-An score. Thrombotic events occurred in 5.2% (95% CI 3.4-7.1%) of patients.. Epoetin zeta is effective in palliation and treatment of CIA in patients with solid tumors. Overall, it is well tolerated and safe even in patients with increased disease burden.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Retrospective Studies

Topics: Anemia; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Neoplasms

Anaemia is common in cancer patients, with treatments including epoetins and blood transfusions. Although an increased risk of venous thromboembolism (VTE) has been associated with both therapeutics, studies comparing the risk of VTE between epoetins and transfusions in cancer patients are lacking.. A nested case-control study investigated this risk using the German Pharmacoepidemiological Research Database. Cohort members were incident cancer patients receiving first time treatment with epoetin or transfusion. A subcohort including only patients receiving chemotherapy was created, since the formally approved indication of epoetins is chemotherapy-induced anaemia. Cases were defined as patients developing VTE. For each case up to 10 gender- and age-matched controls were selected from the cohort. Multiple confounder adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for VTE and recent treatment with epoetins or transfusions (last 28 days before index date) compared with past anti-anaemic treatment were calculated by conditional logistic regression.. Among 69 888 patients receiving first time treatment with epoetin or transfusion, 3316 VTE cases were identified. The aOR for VTE was 1.31 (95% CI 1.03, 1.65) for epoetins, 2.33 (95% CI 2.03, 2.66) for transfusions, and 2.24 (95% CI 1.34, 3.77) for epoetins and transfusions. Sensitivity analyses with a stricter VTE definition or an expanded time window yielded similar results. In the chemotherapy only subcohort the risk difference between epoetins and transfusions could not be verified (aOR 1.48, 95% CI 1.10, 1.98 vs. aOR 1.80, 95% CI 1.49, 2.19). Our study confirmed known VTE risk factors including previous VTE (aOR 14.76, 95% CI 12.79, 17.03) or surgery (aOR 1.83, 95% CI 1.67, 2.01). Epoetin-associated risk decreased after a safety warning by the European Medicines Agency setting maximum haemoglobin target values to 12 g dl(-1) .. Transfusions could be associated with a higher VTE risk than epoetins in cancer patients. Moreover, current prescribing patterns may have decreased the VTE risk for epoetins.

Topics: Aged; Case-Control Studies; Combined Modality Therapy; Erythropoietin; Female; Humans; Male; Neoplasms; Risk Factors; Transfusion Reaction; Venous Thromboembolism

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Iron; Neoplasms; Recombinant Proteins; Treatment Outcome

Topics: Anemia; Breast Neoplasms; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Standard of Care

Recombinant human erythropoietin (rhuEpo) is used clinically to treat anaemia. However, rhuEpo-treated cancer patients show decreased survival rates and erythropoietin receptor (EpoR) expression has been found in patient tumour tissue. Thus, rhuEpo application might promote EpoR(+) tumour progression. We therefore developed the positron emission tomography (PET)-probe (68)Ga-DOTA-rhuEpo and evaluated its performance in EpoR(+) A549 non-small-cell lung cancer (NSCLC) xenografts.. (68)Ga-DOTA-rhuEpo was generated by coupling DOTA-hydrazide to carbohydrate side-chains of rhuEpo. Biodistribution was determined in tumour-bearing mice 0.5, 3, 6, and 9 h after probe injection. Competition experiments were performed by co-injecting (68)Ga-DOTA-rhuEpo and rhuEpo in five-fold excess. Probe specificity was further evaluated histologically using Epo-Cy5.5 stainings.. The blood half-life of (68)Ga-DOTA-rhuEpo was 2.6 h and the unbound fraction was cleared by the liver and kidney. After 6 h, the highest tumour to muscle ratio was reached. The highest (68)Ga-DOTA-rhuEpo accumulation was found in liver (10.06 ± 6.26%ID/ml), followed by bone marrow (1.87 ± 0.53%ID/ml), kidney (1.58 ± 0.39%ID/ml), and tumour (0.99 ± 0.16%ID/ml). EpoR presence in these organs was histologically confirmed. Competition experiments showed significantly (p < 0.05) lower PET-signals in tumour and bone marrow at 3 and 6 h.. (68)Ga-DOTA-rhuEpo shows favourable pharmacokinetic properties and detects EpoR specifically. Therefore, it might become a valuable radiotracer to monitor EpoR status in tumours and support decision-making in anaemia therapy.. • PET-probe (68) Ga-DOTA-rhuEpo was administered to assess the EpoR status in vivo • (68) Ga-DOTA-rhuEpo binds specifically to EpoR positive organs in vivo • Tumour EpoR status determination might enable decision-making in anaemia therapy with rhuEpo.

Topics: Animals; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Epoetin Alfa; Erythropoietin; Female; Heterografts; Humans; Lung Neoplasms; Mice; Mice, Nude; Neoplasms; Neoplasms, Experimental; Positron-Emission Tomography; Receptors, Erythropoietin; Recombinant Proteins; Tissue Distribution

Few studies have investigated the effects of exercise on modulation of host factors in cancer patients. We investigated the efficacy of chronic aerobic training on multiple host-related effector pathways in patients with solid tumours.. Paired peripheral blood samples were obtained from 44 patients with solid tumours receiving cytotoxic therapy and synthetic erythropoietin (usual care; n=21) or usual care plus supervised aerobic training (n=23) for 12 weeks. Samples were characterised for changes in immune, cytokine and angiogenic factors, and metabolic intermediates. Aerobic training consisted of three supervised cycle ergometry sessions per week at 60% to 100% of peak oxygen consumption (VO2peak), 30-45 min per session, for 12 weeks following a nonlinear prescription.. The between-group delta change in cardiopulmonary function was +4.1 ml kg (-1) min(-1), favouring aerobic training (P<0.05). Significant pre-post between-group differences for five cytokine and angiogenic factors (HGF, IL-4, macrophage inflammatory protein-1β (MIP-1β), vascular endothelial growth factor (VEGF), and TNF-α) also favour the aerobic training group (P's<0.05). These reductions occurred in conjunction with nonsignificant group differences for T lymphocytes CD4(+), CD8(+), and CD8(+)/CD45RA (P<0.10). For these factors, circulating concentrations generally increased from baseline to week 12 in the aerobic training group compared with decreases or no change in the usual care group. No significant changes in any metabolic intermediates were observed.. Aerobic training alters host availability of select immune-inflammatory effectors in patients with solid tumours; larger confirmatory studies in more homogenous samples are warranted.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cardiovascular Physiological Phenomena; Clinical Trials as Topic; Combined Modality Therapy; Erythropoietin; Exercise Test; Exercise Therapy; Female; Humans; Male; Middle Aged; Neoplasms; Oxygen Consumption; Pilot Projects

Preoperative anemia in patients with cancer is highly prevalent, is associated with increased perioperative morbidity and is a risk factor for transfusion. There is evidence that patients who undergo transfusions have higher morbidity, increased cancer recurrence and poorer survival. The pathophysiology of anemia is multifactorial, with an inflammatory component to which chronic blood loss and nutritional deficiencies can be associated. Therefore, preoperative anemia in patients with cancer should be treated appropriately, given that there is sufficient time in the preoperative period. Of the currently available options, parenteral iron is an effective alternative, especially for those types of cancer that have an associated hemorrhagic component.

Topics: Anemia; Biomarkers; Blood Loss, Surgical; C-Reactive Protein; Erythropoietin; Ferritins; Forecasting; Hematinics; Hemoglobins; Humans; Iron; Medical Errors; Neoplasms; Preoperative Care; Recombinant Proteins; Transfusion Reaction

Topics: Animals; Epoetin Alfa; Erythropoietin; Medical Oncology; Neoplasms

We investigated the role of erythropoietin (EPO) in reducing anemia and preventing the development of psychological distress in patients treated with chemotherapy.. This prospective observational study enrolled 591 adult patients receiving EPO at a dose of 30,000 IU administered once weekly for chemotherapy-induced anemia (mean baseline hemoglobin [Hb] level was 9.55 g/dl) over a 12-month period.. The majority of patients (371 [71%] patients) achieved a Hb increase >2 g/dl after 4 weeks of treatment. Interestingly, the nonresponder group had a statistically significant deterioration of their psychological conditions as indicated by psychological distress score (p = 0.01). However, within the group of responders to EPO, the Psychological Distress Inventory score remained unchanged. In the present study, severe side effects associated with EPO were not recorded.. Hb increase, induced by EPO, ameliorates the psychological conditions of cancer patients.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins; Stress, Psychological; Treatment Outcome

Cancer-related anemia has a negative impact on the health-related quality of life (HRQoL). Our aim was to evaluate prospectively the effect of treatment of anemia with an erythropoietin on the hemoglobin level and HRQoL in cancer patients with anemia.. Consecutive patients (N=114) treated for the first time with epoetin (epoetin beta 30000 IU/wk, NeoRecormon®) for anemia during cancer treatment were eligible for study inclusion. Baseline characteristics were collected from patients' records. HRQoL was measured by the generic 15D instrument and fatigue by visual analogue scale (VAS) at baseline and four months from the start of the treatment with epoetin. The majority (87%) of patients had solid tumors; 69% with a metastatic disease and 89% disease with comorbidities.. The mean hemoglobin concentration (SD) in blood increased from 96.6 (8.9) g/L to 112.9 (21.2) g/L, by 16.5 (20.6) g/L (p<0.0001). The mean 15D score rose from 0.72 to 0.77. The change was statistically significant (p=0.0047) and clinically important. The mean fatigue VAS score decreased by 16.0 points, or from 55.4 to 38.4 (+24.4) (p<0.0001).. Correction of anemia increased the health-related quality of life in anemic cancer patients, as measured with the generic 15D instrument and the fatigue VAS.

Topics: Adult; Aged; Anemia; Cohort Studies; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins; Surveys and Questionnaires

This study aimed to evaluate the impact of darbepoetin alfa (DA) on hemoglobin (Hb) levels and quality of life (QoL) in cancer patients with anemia in current daily practice following several revisions of anemia treatment guidelines.. This was a prospective, multi-center, observational study across Germany in non-myeloid cancer outpatients with chemotherapy-induced anemia treated with DA. Age, sex, cancer type, stage, and therapy, performance status, anemia status and treatment, and Hb concentrations were recorded for up to 18 weeks in a web-based registry. Optional QoL assessments were collected at baseline and at the end of DA treatment.. Of 984 eligible patients, 978 had complete anemia data, 492 also had complete QoL data. In the 978 patients, mean age was 64 (standard deviation, SD 12) years, 62% of patients were women. Breast (26%) and gastrointestinal (22%) cancer were most prevalent. Therapy was palliative in 44% of patients and initiated with curative intent in 29%. Mean baseline Hb was 9.5 (SD 0.9) g/dL, which increased by an average of 1.2 g/dL. In 67% of patients Hb increased either to 10-12 g/dL or by ≥2 g/dL; no Hb response was seen in 219 patients (22%); increases of 0 to 1, >1 to 2, and >2 g/dl were seen in 216 (22%), 265 (27%), and 278 (28%) patients, respectively. Anemia treatment did not result in any significant differences of performance status. However, QoL improvements were significantly greater in Hb responders, although a linear relationship with Hb increments was lacking. None of 47 fatal cases was considered related to treatment with DA.. Patients treated with DA in routine clinical practice had increases in Hb and reported improvement in QoL. Due to the uncontrolled design, no conclusions can be made regarding causality to treatment and the clinical relevance of the improvement.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Biomarkers; Darbepoetin alfa; Erythropoietin; Female; Germany; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Practice Guidelines as Topic; Prospective Studies; Quality of Life; Registries; Young Adult

Topics: Animals; Attitude of Health Personnel; Erythropoietin; Hematinics; Humans; Medical Oncology; Neoplasms; Quality of Life; Research Personnel; Survivors

We simulated the budget impact of biosimilar erythropoiesis-stimulating agent (ESA) in EU G5 countries.. Three models were built to estimate the number of patients who could be provided with antineoplastic therapy with rituximab, bevacizumab or trastuzumab from cost savings of biosimilar erythropoietin use in a hypothetical panel of 100,000 patients. The associated number of patients needed to convert to biosimilar ESA to provide such treatments was also calculated.. Under fixed dosing, the savings from 100% conversion were €110,592,159, translating into an additional 9770 rituximab, 3912 bevacizumab, or 3713 trastuzumab treatments. Under weight-based dosing, the savings from 100% conversion were €146,170,333, corresponding to an additional 12,913 rituximab, 5171 bevacizumab or 4908 trastuzumab treatments. The number of patients needed to convert ranged from four to 51.. Using biosimilar ESA for supportive cancer care yields significant savings and increases accessibility to primary antineoplastic therapy in a budget neutral way.

Topics: Anemia; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Bevacizumab; Biosimilar Pharmaceuticals; Drug Costs; Epoetin Alfa; Erythropoietin; European Union; Hematinics; Humans; Models, Economic; Neoplasms; Recombinant Proteins; Rituximab; Trastuzumab

The clinical blood analysis implemented at modern hematological analyzers can be used as a foundation for primary differentiated diagnostic of anemic syndrome related to true and functional iron deficiency in oncologic patients. The normocyte normochromic anemia with normal and higher level of hemoglobin of reticulocytes (RET-HE) testifies presence in higher degree of anemia of chronic diseases which is more often combined with higher content of serum ferritin (Ferr), lower level of soluble receptors of ferritin (sTfR) and production of erythropoietin (EPO) inadequate to anemia degree. The microcyte hypochromic anemia can be present both under iron-deficient anemia and under functional iron deficiency as a result of its blocking in macrophages under anemia of chronic diseases in oncologic patients. Hence the differentiated diagnostic of these states demands additional analysis of content of serum ferritin, soluble receptors of ferritin and production of erythropoietin.

Topics: Anemia, Iron-Deficiency; Automation, Laboratory; Blood Chemical Analysis; Diagnosis, Differential; Erythropoietin; Ferritins; Iron-Binding Proteins; Neoplasms; Receptors, Cell Surface

Anemia is a major cause of morbidity in cancer. Erythropoiesis stimulating agents (ESA) are a mainstay of treatment, although some patients lack response for unknown reasons. Recently, ESA dosing recommendations have changed and iron is increasingly used as an adjunct. Due to these changes, potential laboratory predictors of response were re-evaluated.. This was a multi-center, observational study in cancer outpatients developing anemia under standard chemotherapy without absolute iron deficiency. For up to 12 weeks, laboratory data was collected while patients were treated with darbepoetin α (DA) either alone or along with intravenous iron. Baseline erythropoietin (Epo), changes in soluble transferrin receptor (sTfR) and in hemoglobin (Hb) early after treatment initiation were re-evaluated as response predictors, based on logistic regression models.. Overall, 279 patients (mean age 66.1 years, 59.5% female) entered the study; 171 (61%) received at least one iron dose along with DA. Response and its predictability hardly increased through adjunct iron, although baseline ferritin <100 mg/L resulted in a 10 times higher probability of response to the combination than to ESA alone. Baseline Epo had low predictive value, regardless of tumor type or use of adjunct iron, although it varied with sex and age. If criteria for all three - Epo, sTfR, and Hb - were met, probability of preventing transfusions was 97%, dropping to 44%, if all three failed.. Changes in ESA treatment recommendations had no impact on the predictability of response. Best prediction is still based on the immediacy of Hb increase.

Topics: Aged; Anemia; Antineoplastic Agents; Darbepoetin alfa; Erythropoiesis; Erythropoietin; Female; Humans; Iron; Male; Middle Aged; Neoplasms; Prospective Studies

The erythropoiesis-stimulating agents (ESAs), darbepoetin alfa (DA), and epoetin alfa (EA) differ with respect to dosing schedule in chemotherapy-induced anemia. DA can be administered less frequently than EA, which may increase synchronicity between chemotherapy and ESA schedules. This study compared DA and EA with respect to frequency of synchronization and frequencies of total and ESA healthcare visits in current clinical practice.. A retrospective analysis of ESA utilization during ESA episodes of care was conducted on all cancer patients identified in the SDI health oncology electronic medical records database who underwent chemotherapy and received ESA therapy from July 1, 2007 to March 31, 2010 (n = 6522 DA, n = 3,439 EA).. The frequency of synchronization (chemotherapy and ESA therapy on the same day) was higher with DA (67 %) than EA (58 %) (p < 0.001). The odds that an ESA administration was synchronized with chemotherapy were higher with DA compared with EA (odds ratio = 1.46, 95 % CI: 1.37, 1.54). Compared with EA, DA patients had 2.3 fewer visits with an ESA administration (p < 0.001) and 3.0 fewer total visits (p < 0.001).. Compared with patients receiving EA, DA patients were more likely to have an ESA administration on the same healthcare visit as chemotherapy and had fewer visits for any cause or for ESA administration. These results suggest that through greater synchronization of ESA and chemotherapy administrations, DA may reduce patient and practice burden and healthcare utilization.

Topics: Adolescent; Adult; Aged; Ambulatory Care Facilities; Anemia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Appointments and Schedules; Darbepoetin alfa; Databases, Factual; Drug Administration Schedule; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Retrospective Studies; Young Adult

The PERFORM Questionnaire is a 12-item scale developed for assessing fatigue in cancer patients in the clinical practice. It has advantages over other tools in that it is short and includes beliefs and attitudes of patients about fatigue. It was psychometrically validated in cancer patients with and without anemia.. We evaluated the usefulness of the PERFORM scale to measure fatigue in a large study focusing exclusively on anemic patients.. This was an observational, multicenter, prospective, 3-month study in cancer patients with hemoglobin (Hb)≤11 g/dl. Fatigue was assessed using the PERFORM questionnaire. The overall score ranges from 12 (no fatigue) to 60 (maximum fatigue).. We included 667 patients: 54.1 % women, mean age 60 (standard deviation, 12) years. A highly significant, but mild correlation was observed between low baseline Hb and high patient perception of fatigue (r with PERFORM score=-0.215, p < 0.0001). Of the patients, 65.8 % improved Hb level during follow-up (increase of ≥1 g/dL and/or achieving >11 g/dL), which translated into a significant improvement in the PERFORM score [mean (95 % confidence interval (CI)] change, -1.2 (-0.04 to -2.4), whereas more fatigue was observed in patients without improvement in Hb [change (95 % CI) in PERFORM, +3.3 (1.5 to 5)]. In a multivariate linear regression analysis, the independent factors associated to fatigue at 3 months were a low Hb level, a low Karnofsky index, active chemotherapy, cancer treatment with palliative intention, and transfusion need in the last 3 months.. Minimal increases or decreases in Hb of ≥1 g/dL were associated with meaningful changes in patient-perceived fatigue as measured with the PERFORM questionnaire. In addition to anemia severity, other factors such as active chemotherapy and advanced disease contribute to perception of fatigue by cancer patients.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Blood Transfusion; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Karnofsky Performance Status; Male; Middle Aged; Neoplasms; Prospective Studies; Psychometrics; Surveys and Questionnaires; Young Adult

Inhibition of vascular endothelial growth factor (VEGF) signaling increases red blood cell (RBC) counts, and erythropoiesis markers have been proposed to guide antiangiogenic therapy in humans. We analyzed RBC measurements in patients enrolled in three studies: a phase II trial of axitinib in thyroid cancer; a study of sorafenib in advanced solid tumors; and a randomized trial of fluorouracil, hydroxyurea, and radiation with and without bevacizumab for head and neck cancer. In the sorafenib trial, plasma erythropoietin concentrations were measured at baseline, day 8, and day 35. Over the first 84 days of treatment, RBC counts increased for each day on sorafenib (2.7 M/μL [95% confidence interval (CI), 1.5-3.9]) and axitinib (4.3 M/μL [95% CI, 2.2-6.5]). RBCs declined over the first 68 days of cytotoxic chemoradiotherapy alone (-12.8 M/μL per day [95% CI, -15.7 to -9.8]) but less so with added bevacizumab (-7.2 M/μL per day [95% CI, -9.5 to -4.9]). Erythropoietin levels increased, on average, by 9.5 mIU/mL between day 8 and day 35 of sorafenib exposure. No significant relationships between elevations in RBCs and changes in volume status or blood pressure or between elevations in erythropoietin and smoking status were found. VEGF signaling inhibition is associated with increased RBC and erythropoietin production in humans. The effects of these changes are subtle at physiologic doses and are unlikely to be clinically useful biomarkers for guiding the administration of or predicting treatment responses to VEGF pathway inhibitors.

Topics: Axitinib; Blood Pressure; Clinical Trials as Topic; Combined Modality Therapy; Erythrocyte Count; Erythropoiesis; Erythropoietin; Fluorouracil; Humans; Imidazoles; Indazoles; Neoplasms; Niacinamide; Phenylurea Compounds; Signal Transduction; Sorafenib; Vascular Endothelial Growth Factor A

Cancer-associated cachexia is characterized, among other symptoms, by a dramatic loss of both muscle and fat. In addition, the cachectic syndrome is often associated with anemia. The object of the present investigation was to assess the effects of erythropoietin (EPO) treatment on experimental cancer cachexia models. The results clearly show that, in addition to the improvement of the hematocrit, EPO treatment promoted a partial preservation of adipose tissue while exerting negligible effects on muscle loss. Administration of EPO to tumor-bearing animals resulted in a significant increase of lipoprotein lipase (LPL) activity in adipose tissue, suggesting that the treatment favored triacylglycerol (TAG) accumulation in the adipose tissue. In vitro experiments using both adipose tissue slices and 3T3-L1 adipocytes suggests that EPO is able to increase the lipogenic rate through the activation of its specific receptor (EPOR). This metabolic pathway, in addition to TAG uptake by LPL, may contribute to the beneficial effects of EPO on fat preservation in cancer cachexia.

Topics: 3T3-L1 Cells; Adipose Tissue; Animals; Cachexia; Cell Differentiation; Cell Proliferation; Disease Models, Animal; Erythropoietin; Male; Mice; Muscle, Skeletal; Neoplasms; Rats; Receptors, Erythropoietin

The aim of this study was to examine the rate and timing of hemoglobin decline from <10 g/dL to <9 g/dL in cancer patients receiving chemotherapy.. Pooled data from the placebo arms of six randomized, controlled trials (RCTs) of darbepoetin alfa and data from an aggregated US community oncology clinic electronic medical records (EMR) database were analyzed. Patients had baseline hemoglobin ≥10 g/dL (RCTs) or baseline hemoglobin between ≥10 g/dL and <11 g/dL (EMR episodes) that declined to <10 g/dL at least once during the study period. The proportion of patients/episodes with hemoglobin decline to <9 g/dL by 3, 6, and 9 weeks without erythropoiesis-stimulating agents was estimated from data in each of the data sources, as was the rate of transfusions in the RCTs.. Data from 411 patients receiving placebo in the RCTs and 10,523 patients (10,942 episodes) in the EMR database were analyzed. Forty percent and 35 % of RCT patients and EMR episodes, respectively, had a hemoglobin decline from <10 g/dL to <9 g/dL at week 3, 54 % and 43 % at week 6, and 58 % and 46 % at week 9. Of patients in the RCTs, 43 % required an RBC transfusion.. Hemoglobin can rapidly decline in cancer patients receiving chemotherapy with hemoglobin levels around 10 g/dL, particularly in patients ≥65 years of age. The rapid rate of hemoglobin decline in these patients should be considered for optimal anemia management.

Topics: Aged; Anemia; Confidence Intervals; Darbepoetin alfa; Databases, Factual; Erythropoiesis; Erythropoietin; Female; Hematinics; Hemoglobin A; Humans; Male; Middle Aged; Neoplasms; Randomized Controlled Trials as Topic; United States

There is no consensus in the oncology community about the optimal model for anticoagulation management of ambulatory cancer patients. To understand oncologists' preferences regarding anticoagulation management, we compared the characteristics of patients referred to an oncology-oriented anticoagulation management service with "usual care" patients managed by the patient's primary oncologist.. We performed a retrospective medical record review of ambulatory oncology patients' anticoagulation care at a comprehensive cancer center. We examined the characteristics of 33 patients anticoagulated before implementation of a dedicated oncology anticoagulation management service. We compared this group with 33 patients managed by the anticoagulation management service and with 39 usual care patients managed by the primary oncologist after the anticoagulation management service was created. We also examined differences in laboratory test utilization, time in the therapeutic range (for patients anticoagulated with warfarin), and anticoagulation-related adverse events during a 3-month assessment period.. Anticoagulation management service patients were more likely to be treated for hematologic malignancies, use erythropoietin stimulating agents, and require warfarin management for previous venous thromboembolic disease compared to usual care patients. In contrast, oncologists were more likely to manage anticoagulation care of patients with advanced solid tumors undergoing active chemotherapy. Anticoagulation management service and usual care patients on warfarin therapy had comparable time in the therapeutic range and complication rates.. Oncologists selectively referred patients to the anticoagulation management service. Anticoagulation management service patients' warfarin control and complication rates were comparable to care provided by the primary oncologist, suggesting that an oncology-specific anticoagulation management service may be a feasible and effective option for anticoagulation management of ambulatory oncology patients.

Topics: Adult; Aged; Aged, 80 and over; Ambulatory Care; Anticoagulants; Blood Coagulation Tests; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Oncology Service, Hospital; Physicians; Practice Patterns, Physicians'; Retrospective Studies; Warfarin

To examine epoetin alfa (EPO) and darbepoetin alfa (DARB) treatment patterns and erythropoiesis stimulating agent (ESA) costs in patients with cancer receiving chemotherapy (CRC), and to compare the results observed in the pre-matched total study population (TSP) with a propensity score matched population (PSMP).. A medical claims analysis was conducted from 1 January 2004 through 31 July 2009 using the HealthCore Integrated Research Database. Patients were at least 18 years old, newly initiated on EPO or DARB, received ≥ 2 ESA doses, and had ≥ 1 claim for cancer and chemotherapy proximate to ESA treatment. Patients were matched using propensity scores. January 2010 Wholesale Acquisition Cost was used to calculate drug cost. Mean cumulative ESA dose and drug costs were evaluated in the TSP and PSMP.. 4921 EPO and 9173 DARB patients with CRC were identified. In the TSP, mean cumulative ESA doses were EPO: 398,770 units and DARB: 1508 mcg, with similar treatment durations for each. Mean cumulative drug costs were EPO: $6041 and DARB: $7861 (30% higher for DARB). The cumulative dose ratio (EPO units: DARB mcg) was 264:1. The PSMP analysis identified 4831 ESA treated CRC patients in each group. Mean drug costs were EPO: $6055 and DARB: $7863 (30% higher for DARB). The observed dose ratio (EPO units: DARB mcg) was 265:1.. In both analyses, the costs of DARB were higher, even after accounting for baseline differences in the PSMP. Similar trends in dose ratios were also observed in both groups.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Cohort Studies; Darbepoetin alfa; Databases, Factual; Dose-Response Relationship, Drug; Drug Costs; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Propensity Score; Recombinant Proteins; Retrospective Studies

To assess the clinical and economic outcomes among patients with chemotherapy-induced anemia (CIA) treated with United States Food and Drug Administration-approved fixed dosing regimens of erythropoiesis-stimulating agents (ESA).. Data were employed from the Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (DOSE) registry to evaluate CIA patients who were initiated on either epoetin alfa (EPO) 40,000 Units (U) or darbepoetin alfa (DARB) 500 micrograms (mcg) between January 1, 2006 and May 8, 2009. Study measurements included ESA treatment dose and dose ratio, changes in hemoglobin (Hb) levels from baseline, and cumulative ESA costs.. Five hundred forty patients treated in 44 clinical centers were evaluated, of which 420 were initiated on EPO 40,000 U and 120 were initiated on DARB 500 mcg. Both cohorts had similar baseline characteristics, although EPO patients were less likely than DARB patients to have received iron supplementation before ESA initiation (11.4% EPO vs. 20.0% DARB, p = 0.015). The EPO-to-DARB dose ratio based on cumulative ESA dose was 169:1 (U EPO: mcg DARB). EPO patients showed statistically greater Hb improvement compared to DARB patients, and compared to EPO patients, a greater proportion of DARB patients required a blood transfusion (13.9% EPO vs. 22.5% DARB, p = 0.026). Mean cumulative ESA cost was significantly lower for EPO patients than DARB patients ($4,261 EPO vs. $8,643 DARB, p < 0.0001).. These findings reported that patients with CIA achieved more favorable clinical and economic outcomes if initiated with EPO 40,000 U vs. DARB 500 mcg.

Topics: Aged; Anemia; Antineoplastic Agents; Darbepoetin alfa; Dietary Supplements; Dose-Response Relationship, Drug; Drug Costs; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Iron; Male; Middle Aged; Neoplasms; Prospective Studies; Recombinant Proteins; Registries; Treatment Outcome

This analysis examined the effects of darbepoetin alfa on hemoglobin and fatigue outcomes in patients with cancer using latent growth curve modeling (LGM).. Data from 4 clinical trials of darbepoetin alfa in lung cancer (2 studies; n = 547; n = 288), lymphoproliferative malignancies (n = 339), and non-myeloid malignancies (n = 320) were analyzed separately. Fatigue was assessed using the FACT-Fatigue (FACT-F) scale. Effects of darbepoetin alfa on changes in hemoglobin and FACT-F scores were evaluated using LGM, controlling for age, gender, Eastern Cooperative Oncology Group performance status, health status, and total transfusions.. Patients receiving darbepoetin alfa had higher rates of change in hemoglobin (standardized regression coefficient [[Formula: see text]] = 0.30 to 0.53, all P < 0.05) than placebo. Patients with greater rates of change in hemoglobin reported improvements in fatigue outcomes ([Formula: see text] = 0.28 to 0.59, all P < 0.05). The total standardized effect of darbepoetin alfa on fatigue outcomes corresponded to a mean change of 0.9 to 3.5 points in FACT-F scores, with one trial demonstrating changes exceeding the minimal important difference of 3 points.. Darbepoetin alfa improved hemoglobin which was associated with improved fatigue across the 4 trials. Clinically, meaningful improvement in fatigue was seen in 2 trials. More complex statistical analysis models of treatment may assist in understanding the effects of erythropoiesis-stimulating agents on patient-reported outcomes.

Topics: Aged; Anemia; Darbepoetin alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome

To investigate the patterns of use of darbepoetin alfa in Spanish centers, and to evaluate its effectiveness in the treatment of chemotherapy-induced anemia under clinical practice conditions.. This was an observational, retrospective, multicenter study in adult patients with non-myeloid malignancies who initiated chemotherapy and darbepoetin alfa. Data was collected for up to 16 weeks or until treatment discontinuation.. A total of 685 patients (72.7% with solid tumors and 27.3% with hematologic malignancies) were included in the study. Median age was 64.7 years (range 18.5-88.9 years), 50.7% were women, 82.4% had ECOG status 0-1 and 80.5% had stage III/IV cancer. At darbepoetin initiation, mean hemoglobin (Hb) was 100 g/L (SD 10), with 11.0% and 23.1% of patients below 90 g/L in solid and hematologic malignancies, respectively. A decrease in transfusion requirements was observed between weeks 5-16 with respect to weeks 0-16 (13.3% [95% CI: 10.7 to 15.9] versus 19.0% [95% CI: 16.0 to 22.0]). Hb levels were significantly increased during the treatment (mean change of 10.4 g/L for solid tumors [p < 0.001], and 16.6 g/L for hematologic malignancies [p < 0.001]). The percentage of patients with baseline Hb level <110 g/L who achieved an Hb level ≥110 g/L during the study was 66.5% (95% CI: 62.5% to 70.5%). Six serious adverse reactions were considered related to darbepoetin alfa (thromboembolic events, 1.0%).. With the limitation of a retrospective design, our results suggest that darbepoetin alfa is a well tolerated treatment that increases hemoglobin levels and reduces the need for transfusion in cancer patients receiving chemotherapy in clinical practice.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Darbepoetin alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Retrospective Studies; Treatment Outcome; Young Adult

ESA therapy can increase hemoglobin, decrease blood transfusions, and improve quality of life in patients with chemotherapy induced anemia (CIA). Despite its benefits, ESA therapy increases the risk of venous thromboembolism (VTE) in cancer patients by 50% and can also cause iron restricted erythropoiesis in CIA patients, which may augment the tendency to develop VTE. We postulated that thrombocytosis, a risk factor for VTE in cancer patients, in CIA patients on ESA therapy might be a result of ESA induced iron restricted erythropoiesis. We performed a retrospective analysis of 187 CIA patients who were randomized to receive weekly Epoetin and IV ferric gluconate, oral ferrous sulfate, or no iron for 8 weeks. Nineteen patients experienced 29 VTEs, and patients, whose platelets increased to ≥350,000 cells/uL were three times more likely to experience a VTE (OR 2.9, P = 0.036, logistic regression) with a four times greater incidence of VTE (IRR 4.4, P = 0.001, Poisson regression). Patients treated with IV iron were significantly less likely to develop platelets of ≥350,000 cells/uL (IRR 0.7, P = 0.013, Poisson regression) and had a decreased incidence of VTE. Our study suggests that ESA associated VTE in CIA patients may be, in part, related to the thrombocytosis of ESA induced iron restricted erythropoiesis and may be countered by IV iron.

Topics: Aged; Anemia; Anemia, Iron-Deficiency; Antineoplastic Agents; Double-Blind Method; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Ferric Compounds; Ferrous Compounds; Hematinics; Hemoglobins; Humans; Iron; Male; Meta-Analysis as Topic; Middle Aged; Multicenter Studies as Topic; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Thrombocytosis; Thrombophilia; Venous Thromboembolism

Topics: Altitude; Animals; Erythropoietin; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Mice; Mitochondria; Neoplasms; Signal Transduction

To evaluate the effectiveness of a biosimilar erythropoiesis-stimulating agent (Binocrit) for the treatment of patients with cancer and chemotherapy-induced anemia in real-life clinical practice.. Data were collected retrospectively from patients at five European centers (in France, Italy, The Netherlands, Romania and Spain) who received treatment with Binocrit. Hemoglobin (Hb) levels were recorded at regular intervals during Binocrit therapy for up to 26 weeks. Hb response (an increase of ≥ 1 g/dl in 4 weeks or a Hb level in the range 10-12 g/dl during the study) was assessed in patients with a Hb level ≥ 8.5 g/dl at the start of therapy who received treatment for at least 6 weeks. Hb response rates in patients who did and did not receive intravenous (iv.) iron were also assessed, and data on any serious unexpected adverse events were collected.. Among evaluable patients (n = 113), 79% achieved a Hb response. Response rates were similar among evaluable patients who received an initial Binocrit dose of 30,000 or 40,000 IU/week (81 vs 78%; p = not significant). The Hb response rate was significantly greater in patients who received iv. iron than in patients who did not receive iv. iron (93 vs 77%; p < 0.05). No serious unexpected adverse events were reported.. Use of the biosimilar erythropoiesis-stimulating agent Binocrit is effective and safe for the treatment of patients with cancer and chemotherapy-induced anemia. Supplementation with iv. iron increases the response rate compared with oral or no iron supplementation.

Topics: Aged; Anemia; Antineoplastic Agents; Biosimilar Pharmaceuticals; Erythropoietin; France; Hematinics; Hemoglobins; Humans; Italy; Middle Aged; Neoplasms; Netherlands; Recombinant Proteins; Retrospective Studies; Romania; Spain; Treatment Outcome

Anemia in oncology is no longer seen only as a side effect of chemotherapies. This comorbidity may be multifactorial, clinically and, for example, may be rather chronic when the patient has chronic renal failure associated, resulting in renal anemia. Similarly, the presence of iron deficiency, which can be solely responsible or contributing factor of anemia, is also a factor to be taken into account in both the diagnosis and exploration of anemia and in its treatment, requiring the use of injectable iron complexes for treatment, if necessary in combination with an erythropoiesis agent stimulating.

Topics: Anemia; Antineoplastic Agents; Erythropoiesis; Erythropoietin; Fatigue; Hematinics; Humans; Iron; Iron Deficiencies; Iron, Dietary; Kidney Failure, Chronic; Neoplasms; Practice Guidelines as Topic

The CHOICE study was a prospective, multicentre, observational study designed to assess levels of adherence in current clinical practice to the European product label and EORTC guidelines for the treatment of chemotherapy-induced anaemia (CIA) with darbepoetin alfa (DA). Here we present data split by tumour types: breast, colorectal, ovarian and lung.. Haemoglobin (Hb) levels and red blood cell transfusion requirements were evaluated among patients with solid tumours in 11 European countries. The primary outcome measure was the proportion of patients with a target Hb level of ≥10-≤12 g/dL.. The full analysis set included 1887 patients (mean ± SD 62.4 ± 11.4 years); 1585 (84%) had a current disease stage of ≥3. Common chemotherapy regimens were non-platinum + non-taxane based (n = 696 [37%]) or platinum + non-taxane based (n = 660 [35%]). Breast cancer (n = 575): The mean ± SD Hb level at baseline was 9.9 ± 0.8 g/dL (n = 568). Target Hb level was reached by 187 (55%) patients. Colorectal cancer (n = 310): At baseline the mean ± SD Hb level was 9.8 ± 0.8 g/dL (n = 306). Target Hb level was reached by 107 patients (56%). Ovarian cancer (n = 301): The mean ± SD Hb level at baseline was 9.7 ± 0.8 g/dL (n = 294). Target Hb level was reached by 81 patients (44%). Lung cancer (n = 701): At baseline the mean ± SD Hb level was 9.8 ± 0.9 g/dL (n = 692). Target Hb level was reached by 142 patients (39%).. Five severe or life-threatening adverse drug reactions were seen (three patients with breast cancer, one patient with colorectal cancer and one patient with ovarian cancer).. Potential bias could not be excluded due to the study's observational nature.. This study demonstrates that the recommendations are adhered to in clinical practice, with the mean starting Hb level <10 g/dL irrespective of tumour type. Furthermore, DA is likely to be effective and well tolerated for the treatment of CIA in patients with breast, colorectal, ovarian or lung cancer.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Breast Neoplasms; Colorectal Neoplasms; Darbepoetin alfa; Erythropoietin; Europe; Female; Hematinics; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Ovarian Neoplasms; Prospective Studies

The CHOICE study was a prospective, multicentre, observational study designed to assess the level of adherence in current clinical practice to the European product label and the EORTC guidelines for the treatment of chemotherapy-induced anaemia with darbepoetin alfa (DA).. Hb levels and red blood cell (RBC) transfusion requirements were evaluated among 1900 patients with solid tumours in 11 European countries. The primary outcome measure was the proportion of patients with a target Hb level of ≥10-≤12 g/dL after 9 weeks' DA treatment.. The full analysis set (FAS) comprised 1887 patients (mean ± SD age 62.4 ± 11.4 years) divided into categories by baseline Hb < 9 g/dL (n = 281); 9-<10 g/dL (n = 770); 10-<11 g/dL (n = 695); ≥11 g/dL (n = 114). The proportion of patients who remained on the study at week 9 achieving the target Hb level was 37% (n = 60), 48% (n = 217), 54% (n = 210) and 38% (n = 23) in the subgroups with a baseline Hb level of <9 g/dL, 9-<10 g/dL, 10-<11 g/dL and ≥11 g/dL, respectively. In the <9 g/dL, 9-<10 g/dL, 10-<11 g/dL and ≥11 g/dL subgroups of the FAS, the number of patients maintaining Hb levels ≥10 g/dL after their first achievement of an Hb value of 10 g/dL was 95 (34%), 372 (48%), 476 (68%) and 87 (76%), respectively. The Kaplan-Meier percentages of patients who required an RBC transfusion from week 5 until end of treatment period were: 29%, 20%, 12% and 17% in the <9 g/dL, 9-<10 g/dL, 10-<11 g/dL and ≥11 g/dL subgroups, respectively. Kaplan-Meier percentages of patients reaching an Hb level of >13 g/dL were 10%, 9%, 21% and 29%, respectively. Potential bias could not be excluded due to the study's observational nature.. DA initiation and target Hb ranges adhered to current guidelines in the majority of patients. Furthermore, this study demonstrates faster achievement of the target range and reduced transfusion requirements are associated with initiation of DA at Hb levels of 9-<10 g/dL and 10-<11 g/dL rather than <9 g/dL.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Breast Neoplasms; Colorectal Neoplasms; Darbepoetin alfa; Erythropoietin; Europe; Female; Guideline Adherence; Hematinics; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Ovarian Neoplasms; Practice Guidelines as Topic; Prospective Studies

Erythropoiesis-stimulating agents (ESAs) have been shown to reduce the need for red blood cell (RBC) transfusions and to improve quality of life for cancer patients with anaemia. However, increased risks of mortality and disease progression have been reported when using ESAs with excessive target haemoglobin levels. In 2007, the United States Food and Drug Administration and Korea Food and Drug Administration issued regulatory alerts for using ESAs in cancer patients.. This retrospective study was performed to evaluate changes in ESA prescribing patterns between 2006 and 2010 and the impact on RBC transfusions in patients with solid tumours.. The Seoul National University Hospital (SNUH) in Korea.. This study includes adult patients with solid tumours who were diagnosed and treated in the SNUH from January 2006 to December 2010. The exclusion criterion was concomitant chronic renal failure. The patients' Hb levels and prescription data for ESAs and RBC transfusions were statistically analysed. The number of inpatient and outpatient solid-tumour patients was also analysed as a baseline. Main outcome measure Prescription data on ESAs and RBC transfusion.. After adjusting for the number of patient visits, the monthly mean ESA doses dispensed decreased by an average of 1,192 mcg per quarter over the last 5 years, and the number of RBC transfusions ordered increased by 3.77 instances per quarter. After correcting for the number of patients, the mean doses of ESA dispensed each month decreased by 3,190 mcg per quarter, and the number of RBC transfusions ordered increased by 9.51 instances per quarter.. During the last 5 years, the number of ESA doses dispensed at SNUH decreased and the number of RBC transfusions at SNUH increased, independent of the number of patients. The reduction in ESA use was thought to be due to the release of the safety alert letter in 2007. However, this study did not analyse other risk factors that may have influenced the number of RBC transfusions (e.g. metastatic cancer, comorbidities, surgery). Still, the results of this study suggest that the decreased ESA doses were relevant to the increased RBC transfusions.

Topics: Anemia; Erythrocyte Indices; Erythrocyte Transfusion; Erythropoietin; Guideline Adherence; Hematinics; Humans; Male; Middle Aged; Neoplasms; Practice Guidelines as Topic; Practice Patterns, Physicians'; Republic of Korea; Retrospective Studies; United States; United States Food and Drug Administration

The algorithm of analysis of blood of oncologic patients with anemic syndrome was elaborated using large clinical sampling (n = 284). It is established that 72% of oncologic patients developed anemia by kind of chronic diseases anemia. However in some patients the anemic syndrome was caused by the iron deficiency The cases of B12 deficient, autoimmune hemolytic anemia were registered and inefficient erythropoiesis under metastatic lesion of bone marrow and myelodysplasia syndromes as well. The high importance of methods of objective evaluation of iron resources (level of ferritin and soluble receptors of transferrin), erythropoietic activity of bone marrow (reticulocytes and reticulocyte indices) and adequate response to anemia degree (level of endogenic erythropoietin). The possibility to detect the concentration of hemoglobin in reticulocytes makes it possible to monitor the restoration of hemoglobin content on early stages of treatment of patient with iron deficiency anemia.

Topics: Aged; Algorithms; Anemia, Iron-Deficiency; Clinical Laboratory Techniques; Erythrocytes; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Receptors, Transferrin; Reticulocyte Count; Reticulocytes

This study investigated adherence to treatment guidelines on cancer-related anaemia and fatigue (CRA/CRF) and factors influencing the choice of intervention.. In this prospective, observational study, 136 cancer patients being treated with chemotherapy in a large community hospital completed a questionnaire at consecutive outpatient visits assessing fatigue (the Functional Assessment of Chronic Illness Therapy-Fatigue) and fatigue-related counselling and advice received. Data on administration of chemotherapy and use of epoetin or blood transfusions were abstracted from the medical records.. Fifty-three percent of patients with severe anaemia (Hb < 10 g/dl) and 6% of patients with less severe anaemia (Hb levels 10-12 g/dl) received treatment (epoetin and/or blood transfusions). Half of the patients with less severe anaemia reported clinically relevant levels of fatigue. More than 50% of all patients received fatigue-related counselling, primarily at the start of chemotherapy. Most counselling was directed at energy conservation. Fatigue was not associated significantly with the use of epoetin or blood transfusion. Patients receiving palliative treatment (17%), male patients (16%) and patients with a low Hb level (<6.2 g/dl, 38%) were treated significantly more often with epoetin.. In daily clinical practice, guidelines concerning the use of epoetin or blood transfusion in severe CRA are adhered to in about half of the cases. In patients with less severe anaemia, the level of fatigue did not play a significant role in the use of epoetin. According to current guidelines, counselling on CRF should be directed primarily at activity enhancement. However, only a minority of patients receive such counselling.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Blood Transfusion; Erythropoietin; Fatigue; Female; Guideline Adherence; Hospitals, Community; Humans; Male; Middle Aged; Neoplasms; Palliative Care; Patient Education as Topic; Practice Guidelines as Topic; Prospective Studies; Severity of Illness Index; Sex Factors

The "normobaric oxygen paradox" is a dual mechanism by which oxygen regulates the expression of the Hypoxia Inducible Factor 1 alpha (HIF-1α). The HIF-1α-depending gene regulation is responsible for many different genetic expressions including EPO and VEGF that are usually expressed in parallel. First, VEGF under-expression could decrease tumor angiogenesis leading to a decrease in tumor growth or even apoptosis of cancer cells. Second, induction of EPO-expression can provide cytoprotection. Altogether, this could be deleterious for cancer cells while helping non-malignant cells (at least neural and cardiac) cells to be protected from the side effects of chemotherapy. Eventually, HIF induction could boost immune response by inflammatory cells, increasing their antitumor activity.

Topics: Administration, Inhalation; Chemotherapy, Adjuvant; Erythropoietin; Gene Expression; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Neoplasms; Neovascularization, Pathologic; Oxygen; Vascular Endothelial Growth Factor A

Anemia, which is a common problem in cancer patients, has a negative effect on survival by decreasing the efficacy of chemotherapy and particularly of radiotherapy, as well as impairing the quality of life (QoL) of patients. Recombinant human erythropoietin (rHuEPO) decreases a patient's need for transfusions and increases their QoL. The aim of this study was to evaluate the effect of weekly single-dose EPO treatment on transfusion rates, QoL, and hemoglobin (Hb) levels. In addition, patients were followed up for a long period to assess the impact of EPO treatment on survival. The study was conducted from December 2001 to December 2002 in patients with newly diagnosed lymphoma or solid tumors using a prospective and controlled design. EPO-β was given as a single dose of 450 U/kg once a week for 12 weeks. The study and control groups included 16 patients each. Hb levels measured in the study group at the 4th, 8th, and 12th weeks were significantly higher than the values recorded before the start of chemotherapy. In the control group, Hb levels post chemotherapy were significantly lower than values recorded prior to treatment. The increased Hb levels in the study group were significant at the 8th and 12th weeks of treatment compared to levels measured prior to treatment. In the control group, Hb levels at the 4th and 8th weeks were significantly lower than pretreatment levels. When the percent increase of Hb levels of the study and control groups with respect to treatment week was compared, the difference was statistically significant at the 4th, 8th, and 12th weeks. Although the increase on the performance scale within each group during treatment was significant in both the study and control groups, the increase was more marked in the study group. The percent increase on the performance scale with respect to week of treatment was higher in the study group than in the control group. In EPO treatment group, side effects were seen in 38% of patients, with 19% being local pain in the injection area, 13% local hyperemia, and 6% headache. The mean follow-up period of the study and control group was 7.03 ± 0.41 (6.0-7.41) and 7.46 ± 0.45 (6.58-7.83) years, respectively; no statistically significant difference existed between these figures. Overall survival at the end of 7 years of follow-up was 68.8% and 81.3% for the study and control groups, respectively. The use of EPO-β in lymphoma and solid tumor patients on a once-weekly regimen (450 U/kg) was determined to

Topics: Adolescent; Anemia; Blood Transfusion; Child; Child, Preschool; Disease-Free Survival; Erythropoietin; Follow-Up Studies; Hemoglobins; Humans; Male; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins; Survival Rate; Time Factors

Topics: Anemia; Darbepoetin alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Randomized Controlled Trials as Topic

Topics: Anemia; Drug Approval; Erythropoietin; Granulocyte Colony-Stimulating Factor; Guidelines as Topic; Humans; Italy; Neoplasms; Neutropenia; Recombinant Proteins

The authors present an analysis of specific features of transfusions of erythrocyte containing media in oncological patients. Special attention was given to necessary selection of donor erythrocytes in performing operations with massive intraoperative blood loss. It considerably contributes to a decreased number of posttransfusional reactions and complications. For the recent five years transfusions of erythrocyte containing media to more than 15 thousand patients with surgical treatment were analyzed. Among them the individual selection of donor blood was fulfilled in 2047 cases. Compatible erythrocytes could not be selected in five cases only. In these patients infusions of Perftoran were used as an oxygen carrier both during operation and at the postoperative period.

Topics: Adult; Anemia; Blood Component Transfusion; Blood Donors; Blood Group Antigens; Blood Group Incompatibility; Blood Loss, Surgical; Blood Substitutes; Erythropoietin; Female; Fluorocarbons; Hematinics; Histocompatibility Testing; HLA Antigens; Humans; Male; Middle Aged; Monitoring, Physiologic; Neoplasms; Quality Improvement; Recombinant Proteins; Retrospective Studies

Traditionally, erythropoietin (EPO) is described as a hematopoietic cytokine, regulating proliferation and differentiation and survival of the erythroid progenitors. The recent finding of new sites of EPO production and the wide spread distribution of EPO receptors (EPO-R) on endothelial cells, cardiomyocytes, renal cells as well as the central and peripheral nervous system raised the possibility that EPO may exert pleiotropic actions on several targets. Indeed studies (mainly preclinical) have documented protective, non-hematopoietic, abilities of EPO in a variety of tissue. However, the data obtained from clinical studies are more skeptical about these properties. This article provides a comprehensive overview of EPO and its derivatives.

Topics: Anemia; Cardiotonic Agents; Cytoprotection; Erythropoietin; Hypertension; Kidney; Neoplasms; Neuroprotective Agents; Receptors, Erythropoietin; Thrombosis

Anemia is one of the most frequent hematological demonstration of malignant diseases, leading to impairment of function in all tissues and organs of cancer patients and associated with serious stress. This major problem may be exacerbated by radiotherapy or chemotherapy. It is characterized by lower hemoglobin (Hb) level or inadequate circulating red blood cells (RBCs). The present study evaluated the effectiveness of treatment guidelines for anemia among solid cancer patients in Penang hospital and to find associations between treatments and anemia onset and severity.. This is a retrospective observational study was conducted on 534 cancer patients with anemia who were admitted to a government hospital on Penang island i.e., Penang General Hospital in the period between 2003 to 2009.. Effectiveness of standard anemia treatment guidelines was not sufficient because correction of anemia was just temporary.. According to the results, erythropoietin must be used as a cornerstone even for patients who suffer from moderate anemia and blood transfusion should be used just for emergency cases when anemia leads to a critical situation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Protocols; Disease Management; Erythropoietin; Female; Humans; Malaysia; Male; Middle Aged; Neoplasms; Practice Guidelines as Topic; Retrospective Studies; Treatment Outcome; Young Adult

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Erythropoietin; Hemoglobins; Humans; Neoplasms; Receptors, Erythropoietin

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Humans; Neoplasms

With the emerging new warnings surrounding the use of erythropoiesis-stimulating agents (ESAs), the pharmacist's role as health educator and risk communicator expands further to include patient scrutiny to check for eligibility and patient monitoring to check for response or toxicity. This review explores the benefits and risks linked to ESAs use, and the proposed role.. ESAs have been increasingly used for the treatment of chemotherapy-induced anemia because of its documented effect on decreasing transfusion dependency. However, their use has been associated with thromboembolic complications, tumor progression, and decreased overall survival. This review covers current recommendations and guidelines that surround ESAs use in the supportive care of cancer patients.. To minimize or prevent the complications associated with ESAs use, cancer patients should be adequately monitored and counseled. This highlights the importance of the pharmacist's involvement to optimize patient care.

Topics: Anemia; Contraindications; Disease Progression; Drug Monitoring; Erythropoiesis; Erythropoietin; Hematinics; Humans; Neoplasms; Patient Education as Topic; Pharmacists; Practice Guidelines as Topic; Professional Role; Quality of Life; Risk Factors; Thromboembolism

Erythropoietin (EPO) is a glycoprotein hormone. This hormone is a growth factor for red blood cells precursors in the bone marrow. The decrease of oxygen partial pressure, a reduced number of erythrocytes caused by bleeding or excessive destruction, or increased tissues oxygen requirements lead to increased secretion of EPO. Its action takes place on bone marrow erythroblastic cells through specific receptors. EPO stimulates the proliferation of red cell precursors stem cells in the bone marrow, thus increasing their production in one to two weeks. The effectiveness of EPO at increasing haemoglobin and improving patients' quality of life has been demonstrated by several studies. However, its use in radiotherapy remains controversial. While tumour hypoxia caused by anaemia is a factor of radio resistance and thus a source of local failure, tumour expression of EPO receptors presents a significant risk for tumour progression and neo-angiogenesis, which would be increased during the administration of EPO. The purpose of this article is to answer the question: is there a place for EPO in combination with radiotherapy in the management of cancer?

Topics: Anemia; Biomarkers, Tumor; Erythropoietin; Humans; Neoplasms; Prognosis; Radiotherapy; Receptors, Erythropoietin; Recombinant Proteins

A number of anaemic cancer patients are not responsive to treatment with recombinant human erythropoietin (rHuEPO). The aim of the present study is to investigate whether serum levels of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6 and additional laboratory parameters, together with clinical variables, can predict the clinical outcome of treatment with rHuEPO in anaemic cancer patients.. Thirty-five cancer patients and 25 healthy controls were enrolled in this study. Patients were treated with epoetin alfa at the dose of 150 IU/kg s.c. three times a week for 12 weeks. If the haemoglobin (Hb) level failed to improve at least 2 g/dl above baseline by week 6 of treatment, dose was increased to 300 IU/kg s.c. for the remainder of the treatment period. All patients filled out the Brief Fatigue Inventory (BFI), a questionnaire for the self-evaluation of cancer-related fatigue. Serum samples from patients and control groups were frozen at -80 degrees C and TNF-alpha, IL-1beta and IL-6 were later examined by enzyme-linked immunosorbent assay.. Fatigued cancer patients had significant higher levels of circulating TNF-alpha, IL-1beta and IL-6 than healthy controls. Responders (Rs) to erythropoietin had significant lower medium levels of TNF-alpha and IL-6 than nonresponders (NRs). Fatigued patients with a general BFI score > or =6 presented higher medium level of cytokines than nonfatigued patients (general BFI score <6), but each group responded similarly to treatment with rHuEPO.. High serum levels of TNF-alpha and IL-6 at the baseline are significantly correlated with a negative response to administration with rHuEPO. Thus, pretreatment evaluation of TNF-alpha and IL-6 serum levels can help to select those patients who are most likely to benefit from treatment with rHuEPO. On the contrary, Hb level, red blood cell count, lactate dehydrogenase and BFI score do not predict the outcome of treatment with rHuEPO.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Interleukin-6; Male; Middle Aged; Neoplasms; Recombinant Proteins; Survival Rate; Treatment Outcome; Tumor Necrosis Factor-alpha

Certain oncology trials showed worse clinical outcomes in the erythropoiesis-stimulating agent (ESA) arm. A potential explanation was that ESA-activated erythropoietin (Epo) receptors (EpoRs) promoted tumor cell growth. Although there were supportive data from preclinical studies, those findings often used invalidated reagents and methodologies and were in conflict with other studies. Here, we further investigate the expression and function of EpoR in tumor cell lines. EpoR mRNA levels in 209 human cell lines representing 16 tumor types were low compared with ESA-responsive positive controls. EpoR protein production was evaluated in a subset of 66 cell lines using a novel anti-EpoR antibody. EpoR(+) control cells had an estimated 10 000 to 100 000 EpoR dimers/cell. In contrast, 54 of 61 lines had EpoR protein levels lower than 100 dimers/cell. Cell lines with the highest EpoR protein levels (400-3200 dimers/cell) were studied further, and, although one line, NCI-H661, bound detectable levels of [(125)I]-recombinant human Epo (rHuEpo), none showed evidence of ESA-induced EpoR activation. There was no increased phosphorylation of STAT5, AKT, ERK, or S6RP with rHuEpo. In addition, EpoR knockdown with siRNAs did not affect viability in 2 cell lines previously reported to express functional EpoR (A2780 and SK-OV-3). These results conflict with the hypothesis that EpoR is functionally expressed in tumors.

Topics: Base Sequence; Cell Line, Tumor; Cell Survival; DNA Primers; Erythropoietin; Female; Gene Expression; Hematinics; Humans; Male; Models, Biological; Neoplasms; Phosphorylation; Receptors, Erythropoietin; Recombinant Proteins; RNA, Messenger; RNA, Neoplasm; RNA, Small Interfering; Signal Transduction

Topics: Anemia; Darbepoetin alfa; Diabetes Mellitus, Type 2; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Iron; Male; Neoplasms; Renal Insufficiency, Chronic; Stroke; Treatment Outcome

Topics: Drug Industry; Erythropoiesis; Erythropoietin; Neoplasms; Pharmacy Service, Hospital; Recombinant Proteins; Risk Management; United States; United States Food and Drug Administration

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Documentation; Epoetin Alfa; Erythropoietin; Health Policy; Hematinics; Humans; Neoplasms; Recombinant Proteins; Risk Management; United States; United States Food and Drug Administration

The combination of chronic kidney disease (CKD), chronic heart failure (HF), and anaemia, the so-called cardio-renal-anaemia syndrome (CRA) is associated with dysregulation of erythropoietin levels and inflammation. Both have been associated with the development of cancer. This study aimed to determine the cumulative incidence of cancer in patients with CRA, as compared with anaemic CKD and control patients.. Patients aged <80 years who attended the nephrology or cardiology outpatient clinics between March 2006 and November 2007 were eligible for inclusion in this retrospective case-control study if haemoglobin <8.1 mmol/L (13 g/dL) and serum creatinine >80 mmol/L (0.90 mg/dL). Medical records dating back to 1996 were reviewed. The relationship between cancer and CRA, chronic HF, CKD, and anaemia was analysed using logistic regression analysis. Data from 1087 patients were reviewed. We identified 348 patients with both CKD and anaemia, of whom 132(38.3%) had CRA. The control group included 264 patients attending the hypertension outpatient clinic. Patients with CRA had a 19% cumulative incidence of cancer compared with 11% for patients with anaemia, CKD and no chronic HF, and 11% in the control group. The odds ratio (OR) for cancer was 1.8(95% CI 1.0-3.2) for the CRA group compared with the control group. Chronic HF was an independent risk factor for cancer after correction for age and gender (adjusted OR 2.0; 95% CI 1.2-3.3, P = 0.007).. The cumulative incidence of cancer among patients with CRA is high compared with controls and to anaemic CKD patients without chronic HF. Chronic HF was an independent risk factor for cancer. These results stress the importance of clarifying the mechanisms involved in the development of cancer in CRA.

Topics: Aged; Anemia; Case-Control Studies; Confidence Intervals; Erythropoietin; Female; Heart Failure; Humans; Incidence; Kidney Failure, Chronic; Logistic Models; Male; Middle Aged; Neoplasms; Netherlands; Odds Ratio; Receptors, Erythropoietin; Retrospective Studies; Risk Factors; Syndrome

Use of erythropoiesis-stimulating agents (ESA) has been reported to increase the incidence of cardiovascular diseases at target Hb levels by more than 12.0 g/dl. The recent TREAT study found an increased incidence of stroke and cancer when maintaining the Hb level at 12.5 g/dl in diabetic patients.. Surveillance of Epoetin-Adverse Events of Stroke and Cancer (SEASCAN) was a cross-sectional study conducted under urgent conditions by the Committee on CKD Initiatives of the Japanese Society of Nephrology. Patients who were at least 18 years old and had CKD stage 4 and 5, namely, eGFR <30 ml/min/1.73 m(2), and who had visited the outpatient department of the participating facilities between December 2009 and January 2010 with at least 6 months of prior medical treatment in the participating facilities were eligible to participate in the study.. Of 7,415 patients with CKD stage 4 and 5, 3,653 (49.3%), 879 (11.9%) and 2,883 (38.9%) patients received no epoetin, epoetin for less than 6 months and epoetin for at least 6 months, respectively. In patients who did not use epoetin, use of epoetin for less than 6 months and use of epoetin for at least 6 months, the numbers of patients with stroke were 38 (1.0%), 8 (0.9%) and 27 (0.9%), respectively, and those with newly diagnosed or exacerbated malignancy were 88 (2.4%), 30 (3.4%) and 71 (2.5%), respectively, demonstrating insignificant associations between outcome and duration of treatment with epoetin (P for trend = 0.666 in stroke and 0.836 in malignancy).. No significant increase in the risk of developing symptomatic stroke and cancer was observed for the use of epoetin in current clinical practice in Japan.

Topics: Aged; Cross-Sectional Studies; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Renal Insufficiency, Chronic; Stroke

Topics: Erythropoiesis; Erythropoietin; Humans; Neoplasms; Neuroprotective Agents; Receptors, Cell Surface; Receptors, Erythropoietin

This prospective, observational study investigated the haematological response to darbepoetin alfa (DA) administered every three weeks for the treatment of anaemia. Response was also assessed according to baseline characteristics including iron, folate and vitamin B12 status.. Anaemic adult patients with malignant non-myeloid cancer, starting or having already undergone chemotherapy received DA on day of inclusionand were followed up for up to 24 weeks. Concentration of haemoglobin (Hb), as well as iron, vitamin B12 and folate status where available, were recorded at inclusion, after a treatment period of 9 weeks and up to a maximum of 24 weeks or cessation of DA treatment, whichever was sooner.. The main outcome measure assessed in this study was the percentage of patients reaching a Hb concentration of at least 11 g/dL at least once at any time during the study.. A total of 2912 patients were included. The mean Hb concentration increased from 10.0 g/dL at inclusion to 11.4 g/dL at 9 weeks and 11.8 g/dL at 24 weeks. In 74.6% of patients the target Hb level of 11.0 g/dL or above was reached. After initiation of DA treatment, 9.5% of patients required a blood transfusion by week 9, and 5.6% thereafter. Vitamin B12 and folate status were unknown for 80.3% of patients and the iron status for 73.2% of patients. Compared with patients who remained untreated for vitamin B12 or folate deficiency, a higher percentage of patients with vitamin status within normal limits achieved the target Hb concentration. However, achievement of target Hb level appeared not to be affected by iron status.. In this study, the mean Hb level increased in anaemic cancer patients treated with DA and the majority of patients achieved the target Hb level. In contrast to the recommendations of guidelines (EORTC) encouraging the measurement of iron and vitamin levels, the present study demonstrated that data were not routinely collected for these factors.

Topics: Aged; Anemia; Antineoplastic Agents; Cohort Studies; Darbepoetin alfa; Dietary Supplements; Erythropoietin; Female; Folic Acid; France; Hematinics; Humans; Iron; Male; Middle Aged; Neoplasm Metastasis; Neoplasms; Prospective Studies; Vitamin B 12

This editorial is focused on the double controversial action of erythropoietin, acting as anticancer agent and as a promoting cancer agent.

Topics: Anemia; Disease Progression; Erythropoietin; Humans; Neoplasms; Receptors, Erythropoietin; RNA, Messenger; Survival Rate

A subgroup analysis comparing elderly (age > or =70 years; n=95) with younger (age <70 years; n=390) patients was performed on data from a prospective, multicenter, open-label study assessing the effects of once-weekly epoetin alfa 40,000 International Units (IU) for 16-20 weeks on hemoglobin (Hb) levels and quality of life (QoL) in anemic adult patients undergoing chemotherapy for solid tumors. There were significant increases in mean Hb levels at 4, 8, 12, 16-20 weeks in both age groups (p<0.0001), but no significant differences between groups (p=0.7). No significant difference was observed in terms of blood transfusion rates across the study between elderly and younger patients (3.2% vs 6.7%, p=0.2). Although QoL was lower in elderly patients at baseline, the relative percentage increases in QoL scores during treatment were similar for both age groups. Thus, once-weekly epoetin alfa was equally effective in treating chemotherapy-related anemia in elderly and younger adult patients, with similar tolerability.

Topics: Age Factors; Aged; Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins

To model the relationship between scores for practicing in congruence (CSs; 0-10) with EORTC guidelines for erythropoietic proteins (EPs) and haemoglobin (Hb) outcomes observed in the validation study of the RESPOND system.. Thirty four patient pairs matched on cancer type and chemotherapy in pre- (retrospective; clinicians not using RESPOND) and post-cohorts (prospective; clinicians using RESPOND) followed over 4 months following EP treatment initiation. CSs quantify the extent that care was guideline-adherent. Linear and logistic regressions controlling for cohort examined Hb outcomes as a function of CSs.. A one-point increase in CS was associated with 0.60g/dL increase in Hb at month 4 (R(2)=0.40) and 0.56g/dL increase in Hb change from month 1-4 (R(2)=0.33). Each one-point increase in CS increased the odds of reaching Hb>or=11g/dL by 3.14 (R(2)=0.42) and Hb>or=12g/dL by 2.77 (R(2)=0.45).. Guideline-adherent EP treatment may improve Hb outcomes but specifically designed outcomes studies are necessary.

Topics: Anemia; Erythropoietin; Guideline Adherence; Hemoglobins; Humans; Linear Models; Logistic Models; Neoplasms; Practice Guidelines as Topic; Prospective Studies; Retrospective Studies; Treatment Outcome

Topics: Anemia; Antineoplastic Agents; Child; Colony-Stimulating Factors; Erythropoietin; Granulocyte Colony-Stimulating Factor; Humans; Neoplasms; Recombinant Proteins

Erythropoiesis is considered as a multistep and tightly regulated process under the control of a series of cytokines including erythropoietin (Epo). Epo activates specific signaling pathways and leads to activation of key transcription factors such as GATA-1, in order to ensure erythroid differentiation. Deregulation leads to a decreased number of red blood cells, a hemoglobin deficiency, thus a limited oxygen-carrying capacity in the blood. Anemia represents a frequent complication in various diseases such as cancer or inflammatory diseases. It reduces both quality of life and prognosis in patients. Tumor necrosis factor alpha (TNFalpha) was described to be involved in the pathogenesis of inflammation and cancer related anemia. Blood transfusions and erythroid stimulating agents (ESAs) including human recombinant Epo (rhuEpo) are currently used as efficient treatments. Moreover, the recently described conflicting effects of ESAs in distinct studies require further investigations on the molecular mechanisms involved in TNFalpha-caused anemia. The present study aims to evaluate the current knowledge and the importance of the effect of the proinflammatory cytokine TNFalpha on erythropoiesis in inflammatory and malignant conditions.

Topics: Anemia; Animals; Cell Differentiation; Cytokines; Erythroid Cells; Erythropoiesis; Erythropoietin; Gene Expression Regulation; Humans; Inflammation; Neoplasms; Tumor Necrosis Factor-alpha

No data exists that directly compares hemoglobin and hematocrit levels between cancer patients with and without occurrence of thrombosis during treatment with erythropoiesis stimulating agents (ESAs).. To determine the association of hemoglobin and hematocrit levels with the occurrence of thrombosis in cancer patients treated with ESAs.. A retrospective case-control study approved by the Institutional Review Board was conducted on cancer patients billed for epoetin or darbepoetin between 1 July 2002 and 30 June 2007. Cases were defined as patients billed for thrombosis while controls were defined as patients not billed for thrombosis.. Sixteen patients had an occurrence of thrombosis (cases) and were matched to 16 patients that did not have an occurrence of thrombosis (controls) based on age, sex, and cancer type. The mean peak hemoglobin levels for cases and controls were 12.6 +/- 1.2 g/dL versus 12.6 +/- 1.4 g/dL (p = 0.9). The mean peak hematocrit levels for cases and controls were 37.3 +/- 3.8% versus 37.9 +/- 4.3% (p = 0.8). For the 16/586 (2.7%) patients with thrombosis, the mean hemoglobin and hematocrit at time of thrombosis were 9.6 +/- 1.0 g/dL and 28.9 +/- 3.1%. A significant identifiable risk factor for thrombosis between the cases and controls was history of thrombosis 31.3% versus 0% (p = 0.04).. There was no statistical difference in peak hemoglobin and hematocrit levels between patients with thrombosis and those without thrombosis. Further study is warranted to determine if these levels are true risk factors for thrombosis.

Topics: Anemia; Anticoagulants; Case-Control Studies; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematocrit; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Retrospective Studies; Risk Factors; Thrombosis; Time Factors

To examine anaemia management in cancer patients treated with erythropoiesis-stimulating agents (ESAs) in Europe.. Retrospective pharmacoepidemiologic study of 2192 patients from 307 centres. Minimum of 3 visits over 8-10 weeks with ESA treatment initiated at visit 1.. Most patients were treated per guidelines, except for low iron supplementation rates. Mean Hb rose from 9.54+/-0.95 g/dl to 10.88+/-1.49 g/dl at visit 3, without concomitant rise in WHO/ECOG score. Response rates were 65.0% (Hb increase (upward arrow) > or = 1 g/dl); 54.3% (Hb increase (upward arrow) > or = 1 g/dl in 8 weeks); 38.9% (haematopoietic response); 33.7% (Hb increase (upward arrow) > or = 2 g/dl) and 18.8% (Hb between 12.0 and 12.9 g/dl). Treatment patterns were guideline congruent, except for (intravenous) iron supplementation. Hb increased by 1.34 g/dl. A net erythropoiesis boost of Hb > or =1 g/dl is attainable in two-thirds of patients and should be condensed to 8 weeks on an individual patient basis. Anaemia management in Europe has improved significantly. The general effectiveness and relative safety of judicious ESA treatment are evident.

Topics: Adult; Aged; Anemia; Drug Administration Schedule; Erythropoietin; Female; Guideline Adherence; Hematinics; Hemoglobins; Humans; Iron; Male; Middle Aged; Neoplasms; Practice Guidelines as Topic; Practice Patterns, Physicians'; Recombinant Proteins; Retrospective Studies; Treatment Outcome; Young Adult

Anemia commonly occurs in cancer patients and results in symptoms such as fatigue which have a profound impact on quality of life. Anemia is also associated with poor treatment outcome and overall survival. Several studies in patients with solid tumors have shown that erythropoiesis-stimulating agents (ESA), such as recombinant erythropoietins, effectively increase hemoglobin levels and reduce the need for emergency blood transfusions, regardless of the type of concomitantly administered chemotherapy. This Italian meeting, sponsored by the Italian Southern Oncological Group (GOIM) and Southern Pananemia Study Group, focused on various aspects of cancer-related anemia and its treatment options.

Topics: Anemia; Animals; Antineoplastic Agents; Erythropoietin; Humans; Italy; Medical Oncology; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins

To evaluate the frequency of chemotherapy-induced myelotoxicity in cancer patients, the related treatment (G-CSF, rHuEPO), and the occurrence of chemotherapy dose reductions, delays or discontinuations.. We retrospectively collected data from 1175 patients who completed at least four chemotherapy courses at 64 Italian Centres. Myelotoxicity was defined as anemia (Hb < 10 g/dL) and neutropenia (ANC < 1500/mm(3)). The study population was divided by age, in 664 adult patients aged < or =65 years and 511 elderly patients, aged > 65 years. The association between events during chemotherapy and myelotoxicity indices were assessed by logistic regression.. The median age of the patients was 64 years. Myelotoxicity was observed in 633 patients (53.9%), anemia (< 10 g/dL) in 263 (22.4%) and neutropenia in 530 (45.1%); 686 patients (58.5%) showed mild anemia (Hb < 12 g/dL). Dose reductions were observed in 199 patients (16.9%), dose delays in 338 (28.7%), and discontinuations in 157 (13.4%), with no significant difference between age groups. Myelotoxicity accounted for 20% of treatment withdrawals with no differences between age groups. G-CSF was administered to 53.4% of the neutropenic patients, and rHuEPO to 53.1% of the anemic patients. Logistic regression analyses showed a significant (P < 0.001) association between chemotherapy dose delays, dose reductions and myelotoxicity. Considering age strata, the association between dose reduction and myelotoxicity was significant. The risk of neutropenia in the adults was higher than in elderly (50.0% vs 38.7%).. Our results show that anemia and neutropenia occur in a substantial proportion of cancer patients receiving chemotherapy, and have an impact on chemotherapy dose delivery. G-CSF and rHuEPO are treatments widely used in about one half of neutropenic and anemic patients. Particular attention should be given to elderly patients, who are at high risk of myelotoxicity and should be carefully evaluated for the prophylactic use of G-CSF and monitored for the appropriate use of rHuEPO.

Topics: Aged; Anemia; Antineoplastic Agents; Bone Marrow; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Humans; Incidence; Male; Middle Aged; Neoplasms; Neutropenia; Prevalence; Recombinant Proteins; Retrospective Studies

Hepcidin is thought to be the central regulator of iron metabolism. Iron deficiency is associated with low hepcidin concentrations, and anemia in patients with cancer is associated with high concentrations of hepcidin.. Our main objective was to assess the potential role of hepcidin for predicting response to epoetin therapy in anemic cancer patients. We also aimed to identify a cutoff value for hepcidin as a potential predictive marker for response to epoetin therapy.. Using data from 525 anemic cancer patients enrolled in 5 studies, we assessed serum hepcidin concentrations in 408 of these patients at baseline and analyzed pooled data from the 408 patients. The analysis population was separated into 2 categories using a threshold hepcidin concentration of 13 nmol/L: low hepcidin (< 13 nmol/L) and high hepcidin (> or = 13 nmol/L).. A significantly higher percentage of responders (defined as hemoglobin increase > or = 10 g/L or > or = 20 g/L from baseline) was observed in the low hepcidin group compared with the high hepcidin group (P = 0.04 for > or = 10 g/L increase and P = 0.009 for > or = 20 g/L from baseline). There was also a statistically significant difference between the 2 groups for hematopoietic response (hemoglobin rise at least once > or = 20 g/L from baseline or at least once > or = 120 g/L) to epoetin therapy (P = 0.0004).. The results of this analysis suggest a potential role of hepcidin serum concentrations in predicting the response to epoetin therapy.

Topics: Aged; Anemia; Antimicrobial Cationic Peptides; Biomarkers; Erythropoietin; Female; Hepcidins; Humans; Male; Middle Aged; Neoplasms

Recombinant erythropoietin-stimulating agents have been used to ameliorate the symptoms of anaemia in cancer patients. However, there have been concerns about an increased risk of thromboembolic events and mortality. This study reviews the usage of epoetin alfa in treating chemotherapy-induced anaemia at the National Cancer Centre Singapore (NCCS), as well as the prescribing and monitoring practices employed.. Cancer patients who have received at least one dose of epoetin alfa at the NCCS between January 1, 2005 and October 15, 2007 were included in this study.. A total of 121 patients were identified and 91 patients were eligible for data collection. The majority of patients manifested breast cancer (30.8 percent) and ovarian cancer (15.4 percent). Over 90 percent of the patients were receiving either chemotherapy or radiotherapy when epoetin alfa was initiated. Epoetin alfa was initiated at a median haemoglobin level of 8.7 (range 7-14.3) g/dL. Approximately 41.8 percent of the patients had a positive response after the initiation of epoetin alfa. Baseline iron studies were performed in 12.1 percent of the patients. Blood pressure was uncontrolled, according to the Singapore Ministry of Health Hypertension guideline, in a substantial number of patients (32.6 percent) prior to the initiation epoetin alfa. There were no documented thromboembolic events.. This study identified a broad range of practices in the utilisation of epoetin alfa at NCCS, which may explain the variable patient response to epoetin alfa. The results of this study will be used to improve the management of chemotherapy-induced anaemia at the institution.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Blood Cell Count; Blood Pressure; Blood Transfusion; Cancer Care Facilities; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobinometry; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Retrospective Studies; Singapore; Utilization Review; Young Adult

Erythropoiesis stimulating agent (ESA) resource utilisation in cancer chemotherapy patients is of importance to managed-care organisations. To understand current real-world utilisation of ESAs, this study examined epoetin alfa (EPO) and darbepoetin alfa (DARB) treatment patterns (dosing and treatment duration), dose ratio and ESA treatment costs.. An analysis of medical claims data from January 2006 through to January 2008 was conducted using the PharMetrics Patient-Centric database of over 85 health plans. Patients included in the study were > or =18 years of age, had at least one cancer claim within 90 days prior to ESA treatment initiation, were newly initiated on EPO or DARB, received at least two doses, and were treated with concomitant chemotherapy (at least one chemotherapy claim during ESA treatment). Mean cumulative ESA dose was used to calculate drug cost (based on April 2008 wholesale acquisition cost) and dose ratio (units EPO : microg DARB).. A total of 4,111 EPO patients and 6,817 DARB patients met inclusion criteria and formed the study population. EPO-treated patients were slightly older (mean age: EPO 63.6, DARB 61.8, p<0.0001) with a greater proportion of women in the DARB-treated group (EPO 60.9%, DARB 64.1%, p=0.0007). The mean treatment duration was slightly longer in the EPO group (EPO 58.4 days, DARB 55.4 days, p=0.0019). The mean cumulative ESA dose administered was EPO 329,129 units and DARB 1,289 microg, resulting in a dose ratio of 255:1 (units EPO:microg DARB). Mean drug cost per treatment episode was significantly lower in the EPO group by $1,768 (EPO $4,321, DARB $6,089, p<0.0001). After controlling for covariates, the incremental cost associated with DARB treatment remained stable and statistically significant (adjusted cost difference: $1,806 per treatment episode higher for DARB patients than EPO, p<0.0001).. This study of 10,928 oncology patients receiving chemotherapy reported a dose ratio of 255:1 (units EPO:microg DARB) with 29% lower treatment cost in the EPO group. These findings are similar to those previously reported from published clinical trials and real-world utilisation studies.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Costs; Drug Utilization; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Insurance Claim Review; Male; Managed Care Programs; Middle Aged; Neoplasms; Recombinant Proteins; Retrospective Studies

Topics: Erythropoietin; Humans; Neoplasms; Risk Factors

Topics: Acetylation; Aging; Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Hypoxia; Cells, Cultured; Erythropoietin; Gene Expression; Gene Expression Regulation; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Liver; Mice; NAD; Neoplasms; Oxidation-Reduction; Sirtuin 1; Sirtuins

To compare the baseline characteristics, episodes of care, and cost of erythropoiesis-stimulating agents among cancer patients in a US managed-care population.. Retrospective analysis of administrative claims data. Episodes of care for patients with cancer receiving erythropoiesis-stimulating agents between January 1, 2004 and January 17, 2006 included all claims for erythropoiesis-stimulating agents with < or = 42 days' gap between claims, plus the duration of therapeutic benefit based on median days between consecutive doses.. Main outcome measures were average weekly dose of erythropoiesis-stimulating agents and costs of therapy.. A total of 15,007 eligible episodes of care (darbepoetin alfa, 7769 episodes [5587 patients]; epoetin alfa 7238 episodes [5157 patients]) were identified. Fewer claims were observed per episode of care for darbepoetin alfa than for epoetin alfa (mean [SD] 3.7 [4.1] vs. 5.3 [6.4]). The median time between consecutive claims was 15 days (darbepoetin alfa) and 8 days (epoetin alfa). The mean (SD) weekly doses were 105 (56) microg (darbepoetin alfa) and 34,242 (28173) U (epoetin alfa), a dose-comparison ratio of 326 : 1. Dose-comparison ratios were sensitive to assumptions about duration of clinical benefit. The mean (95% CI) weekly costs were significantly lower for darbepoetin alfa ($560 [553-567]) than for epoetin alfa ($645 [630-659], p < 0.0001) when duration of clinical benefit was considered.. Significant differences characterize patterns of use of erythropoiesis-stimulating agents. Duration of therapeutic benefit is an important variable in comparing darbepoetin alfa with epoetin alfa; incorporation of this variable in analyses of costs of therapy may have notable effects on calculated treatment costs. Limitations of the study include the potential for database errors or omissions, lack of detailed disease data, and lack of adjustment for differences in the ages and comorbidities of patients.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Darbepoetin alfa; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Health Care Costs; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Retrospective Studies; Treatment Outcome

Two erythropoiesis-stimulating agents (ESAs), epoetin alfa and darbepoetin alfa, are approved for the treatment of chemotherapy-induced anemia in patients with cancer. Randomized controlled trials indicate that the drugs are similarly efficacious, but that the duration of clinical benefit (DCB) ranges from 2 to 7 days for epoetin alfa and from 7 to 21 days for darbepoetin alfa, depending on dose. Given equivalent efficacy, payers are increasingly interested in understanding the cost differences for these 2 drugs.. To examine the impact of different methodological approaches on the cost comparison between epoetin alfa and darbepoetin alfa users, with cancer from a payer perspective.. Episodes of care (episode) were constructed for cancer patients treated with ESAs, using MarketScan claims data. Episodes started with the first ESA claim and ended on the last ESA claim or the claim before a 42-day or longer gap in ESA therapy. Each episode was augmented with an estimated DCB based on the last dose in the episode. Cost was reimbursed amount observed in the claims database. Adjusted weekly cost was estimated using generalized linear models to control for difference in clinical and demographic differences across epoetin alfa and darbepoetin alfa episodes.. Episodes were created in 324 darbepoetin alfa and 342 epoetin alfa users. Darbepoetin alfa users tended to be younger, had more comorbidities, and had advanced cancer (all p < 0.001). After accounting for DCB, the average weekly cost of darbepoetin alfa was significantly lower than that of epoetin alfa ($619 vs $940; p < 0.001). After multivariate adjustment, darbepoetin alfa had lower costs than epoetin alfa in the base case and all alternative approaches.. To reduce the risk of potential bias, DCB and different patient characteristics should be taken into account when using retrospective claims data to conduct cost comparisons between agents that have significant differences in dosing schedule.

Topics: Age Factors; Aged; Anemia; Antineoplastic Agents; Comorbidity; Darbepoetin alfa; Databases, Factual; Drug Costs; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Linear Models; Male; Middle Aged; Neoplasms; Recombinant Proteins; Retrospective Studies

Topics: Erythropoietin; Guideline Adherence; Humans; Meta-Analysis as Topic; Neoplasms; Patient Selection; Practice Guidelines as Topic; Recombinant Proteins; Research Design; Survival Rate

Topics: Anemia; Drug Administration Schedule; Erythropoietin; Hemoglobins; Humans; Neoplasms; Patient Selection; Recombinant Proteins; Survival Rate

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Double-Blind Method; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Hematinics; Humans; Incidence; Male; Neoplasms; Prognosis; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Survival Analysis; Thromboembolism; Treatment Outcome

Erythropoietin (EPO) has been used to correct cancer-related anemia and to improve tumor hypoxia, which both adversely affect the clinical condition of cancer patients and response to radiotherapy. Data available on the effects of EPO treatment in cancer are, however, conflicting. Several clinical studies investigating the influence of EPO treatment have given contradictory results as to whether or not this treatment positively influences survival. In light of these conflicting results, we studied the effects of EPO treatment either alone or in combination with radiotherapy on tumor oxygenation and on the expression pattern of several proteins related to tumor metabolism, survival, and spread in a rat colorectal cancer model. We found a statistically significant upregulation of hexokinase I, N-cadherin, and glucose transporter 3 when EPO treatment was combined with radiotherapy. Because these three proteins have distinct functions in protecting the cell in compromised conditions, these results indicate a detrimental role for the combination of EPO treatment and radiotherapy through the stimulation of tumor-cell metabolism, inhibition of apoptosis, and stimulation of tumor spread and seem to indicate that recombinant human EPO treatment negatively modulates radiotherapy efficacy.

Topics: Animals; Cell Line, Tumor; Cell Nucleus; Combined Modality Therapy; Erythropoietin; Gene Expression Regulation, Neoplastic; Hematocrit; Immunohistochemistry; Male; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms; Oxygen; Radiotherapy; Rats; Treatment Outcome

Erythropoiesis-stimulating agents (erythropoietin and darbepoietin) have been approved to reduce the number of blood transfusions required during chemotherapy; however, concerns about the risks of venous thromboembolism and mortality exist.. We identified patients who were aged 65 years or older in the Surveillance, Epidemiology, and End Results-Medicare database; who were diagnosed with colon, non-small cell lung, or breast cancer or with diffuse large B-cell lymphoma from January 1, 1991, through December 31, 2002; and who received chemotherapy. The main outcome measures were claims for use of an erythropoiesis-stimulating agent, blood transfusion, venous thromboembolism (ie, deep vein thrombosis or pulmonary embolism), and overall survival. We used multivariable logistic regression models to analyze the association of erythropoiesis-stimulating agent use with clinical and demographic variables. We used time-dependent Cox proportional hazards models to analyze the association of time to receipt of first erythropoiesis-stimulating agent with venous thromboembolism and overall survival. All statistical tests were two-sided.. Among 56,210 patients treated with chemotherapy from 1991 through 2002, 15,346 (27%) received an erythropoiesis-stimulating agent. The proportion of patients receiving erythropoiesis-stimulating agents increased from 4.8% in 1991 to 45.9% in 2002 (P < .001). Use was associated with more recent diagnosis, younger age, urban residence, comorbidities, receipt of radiation therapy, female sex, and metastatic or recurrent cancer. The rate of blood transfusion per year during 1991-2002 remained constant at 22%. Venous thromboembolism developed in 1796 (14.3%) of the 12,522 patients who received erythropoiesis-stimulating agent and 3400 (9.8%) of the 34,820 patients who did not (hazard ratio = 1.93, 95% confidence interval = 1.79 to 2.07). Overall survival was similar in both groups.. Use of erythropoiesis-stimulating agent increased rapidly after its approval in 1991, but the blood transfusion rate did not change. Use of erythropoiesis-stimulating agents was associated with an increased risk of venous thromboembolism but not of mortality.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Anemia; Antineoplastic Agents; Blood Transfusion; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Colonic Neoplasms; Confounding Factors, Epidemiologic; Darbepoetin alfa; Erythropoietin; Female; Hematinics; Humans; Lung Neoplasms; Lymphoma, Large B-Cell, Diffuse; Male; Medical Record Linkage; Medicare; Neoplasms; Practice Patterns, Physicians'; Recombinant Proteins; Retrospective Studies; Risk Factors; SEER Program; United States; Venous Thromboembolism

Topics: Anemia; Antineoplastic Agents; Disease Progression; Erythropoietin; Hemoglobins; Humans; Neoplasms; Recombinant Proteins; Thromboembolism

Erythropoiesis-stimulating agents (ESAs) are used in chemotherapy-induced anemia (CIA) with the goal of improving quality of life and preventing RBC transfusions. This retrospective database study compared the three currently available ESAs, epoetin alfa (EPO-A), epoetin beta (EPO-B), and darbepoetin alfa (DARB), regarding costs and outcomes.. Data were obtained from a Belgian longitudinal database, including medical and financial data on cancer patients receiving chemotherapy and ESAs, submitted by 46 Belgian hospitals. Propensity score matching was applied to correct for selection bias. The main effectiveness parameter was defined as transfusion- and anemia-readmission-free survival (TA-free survival) at 3 months. Costs were analyzed taking the health care payer perspective.. Including 1,584 EPO-A, 380 EPO-B, and 429 DARB propensity-matched patients, TA-free survival rates were similar for the three groups (DARB, 84.37%; EPO-A, 84.60%; EPO-B, 84.94%). Overall inpatient costs were euro 16,949 +/- euro 1,025, euro 19,472 +/- euro 901, and euro 19,295 +/- euro 1,048 for DARB, EPO-A, and EPO-B, respectively (DARB versus EPO-A, p < .0001 and DARB versus EPO-B, p = .008). Anemia-associated costs were euro 3,051 +/- euro 218 in the DARB group, compared with euro 3,995 +/- euro144 for EPO-A (p < .0001) and euro 3,752 +/- euro 229 for EPO-B (p = .0132).. To our knowledge, this is the first real-life matched retrospective study comparing ESAs with regard to both costs and effects. For similar patient profiles, the patients in the DARB group consumed the smallest amounts of ESAs, with similar clinical outcomes. These data therefore suggest a greater efficiency of DARB in the treatment of CIA.

Topics: Aged; Anemia; Antineoplastic Agents; Belgium; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Health Care Costs; Hematinics; Humans; Length of Stay; Male; Middle Aged; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Treatment Outcome

In patients with chronic kidney disease and renal failure, hemoglobin levels have been rising in parallel with more intensive use of erythropoiesis-stimulating agents (ESAs). However, several recent studies indicate that raising hemoglobin to normal levels with ESAs can be too much of a good thing. Compared with partial correction, normalization of hemoglobin did not improve outcome, and it may have led to more frequent adverse events. The US Food and Drug Administration (FDA) now recommends a hemoglobin goal in the range of 10 to 12 g/dL.

Topics: Anemia; Antineoplastic Agents; Erythropoiesis; Erythropoietin; Hemoglobins; Humans; Kidney Failure, Chronic; Neoplasms; Receptors, Erythropoietin; Reference Values; Renal Dialysis; Risk Factors; United States; United States Food and Drug Administration

Topics: Anemia; Drug and Narcotic Control; Drug-Related Side Effects and Adverse Reactions; Erythropoietin; Humans; Neoplasms; Receptors, Erythropoietin; United States; United States Food and Drug Administration

Erythropoietin has been shown to shorten survival in cancer patients under certain circumstances. Possible mechanisms are an increase in thrombotic events, tumour progression, and induction of angiogenesis. The FDA advises its use in oncology only as a replacement for blood transfusions in patients receiving chemotherapy. In these patients, a rise in haemoglobin above 7.4 mmol/l should be avoided.

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Humans; Neoplasms; Neovascularization, Pathologic; Survival Analysis; Thrombosis; Treatment Outcome

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Erythropoietin; Ferric Compounds; Hematinics; Humans; Neoplasms

Topics: Age Factors; Anemia; Antineoplastic Agents; Chronic Disease; Disease Progression; Disease-Free Survival; Drug Antagonism; Erythropoietin; Humans; Janus Kinase 2; Neoplasms; Neovascularization, Pathologic; Polypharmacy; Receptors, Erythropoietin; RNA, Messenger

Topics: Activities of Daily Living; Anemia; Antineoplastic Agents; Benzhydryl Compounds; Central Nervous System Stimulants; Counseling; Darbepoetin alfa; Erythropoietin; Exercise; Fatigue; Hematinics; Humans; Meta-Analysis as Topic; Methylphenidate; Modafinil; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Surveys and Questionnaires

The primary aim of this study was to assess whether epoetin alpha (Ea) would improve cognitive performance in a group of anaemic cancer patients receiving chemotherapy. The secondary aim was to confirm the positive impact of Ea on haematological parameters, and quality of life (QOL). Fifty patients with solid tumours and haemoglobin (Hb) <11.0 g/dL received Ea 40,000 units once weekly for 12 weeks and were administered the Mini-Mental State Examination and the European Organization for Research and Treatment of Cancer (QLQ-C30) questionnaire prior to Ea therapy and at study completion. No clinically significant alterations were observed on cognitive function during Ea treatment. Changes in cognitive function were unrelated to Hb change and there were no significant differences in cognitive performance between Ea responders and non-responders. The analyses revealed clinically significant improvements in Hb levels, physical and role function, and clinically meaningful reductions in fatigue. Hb changes were significantly associated with the magnitude of improvement in QOL parameters. The lack of a clinical benefit in cognition observed in this study during Ea treatment may redirect the focus of research from enhancing to maintaining cognitive function, since stability in cognitive performance through time may be as well clinically important.

Topics: Adolescent; Adult; Aged; Anemia; Antineoplastic Agents; Chemotherapy, Adjuvant; Cognition Disorders; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins; Treatment Outcome; Young Adult

In recent years erythropoietic agents have become important tools in the management of anemia in cancer patients, improving hemoglobin (Hb) concentrations, reducing the need for transfusion, and enhancing quality of life. In this prospective and historically controlled study, the effects of epoetin beta on Hb concentrations and red blood cell transfusion needs in children with cancer receiving chemotherapy or radiotherapy have been investigated. Epoetin beta (150 U/kg/day, 3 days a week) was given subcutaneously to 22 children with cancer when Hb concentration < or = 10 g/dL. Data from these patients were compared with those from 20 historical control patients. Hb concentrations were studied weekly in the first 9 weeks, then weekly or fortnightly thereafter. Minimum, maximum, and mean Hb concentrations, frequency of red blood cell transfusion, and the number of red cell packs given were noted. Hb concentrations in weeks 6, 8, and 11 were clearly higher in the study group than the controls. The minimum Hb concentration of the study group was significantly higher than than the control group (7.98 +/- 0.73 [6.70-9.68] g/dL and 7.24 +/- 1.40 [5.50-11.20] g/dL, respectively [p = .038]). A total of 8 units of erythrocyte suspension was given to 4 of the 22 patients in the epoetin group (0.36 unit per patient), while 16 of the 20 patients in the control group received 37 units of erythrocyte suspension in total (1.85 units per patient). The red cell transfusion requirement and the units of transfused erythrocytes per patient were clearly lower in the epoetin group (p < .001 for both of the parameters). No drug-related side effects were noted during epoetin therapy. Epoetin beta therapy provides significant increase in Hb concentrations in children with cancer under anticancer treatment, especially after the sixth week of therapy. Administration of epoetin beta prevents profound decreases in Hb concentrations in the course of therapy and effectively reduces the need for red blood cell transfusions. Epoetin beta was found to be safe and effective in the dosage and the scheme it was used in our study.

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Child; Child, Preschool; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Neoplasms; Radiotherapy; Recombinant Proteins; Treatment Outcome

Aging is associated with increased incidence and prevalence of anemia, leading to a number of adverse health outcomes. These include death, functional dependence, increased risk of therapeutic complications, falls, and dementia. In approximately 30% of cases, anemia in older individuals is due to either relative or absolute erythropoietin (EPO) deficiency. Absolute EPO deficiency may be primary or secondary to declining renal function. Relative EPO deficiency is due to an age-related pro-inflammatory status that reduces the sensitivity of erythropoietic precursors to EPO. Despite this condition of EPO deficiency, the management of anemia of aging with erythropoiesis-stimulating agents (ESAs) is controversial, unless the anemia is due to renal insufficiency. The main concern related to this treatment arises from eight studies of ESAs in cancer, suggesting that ESAs may reduce patient survival in addition to increasing the risk of deep vein thrombosis. The results of these studies contrast with a host of other trials showing the safety of ESAs. The discrepancy may be explained in part by the fact that, in the trials suggesting a detrimental effect of ESAs, the goal was to obtain hemoglobin (Hb) levels higher than 12 g/dL. Because of this concern, correction of anemia in elderly individuals with relative EPO insufficiency should not be attempted outside clinical trials.

Topics: Aged; Anemia; Drug Therapy; Erythrocyte Transfusion; Erythropoietin; Hematinics; Humans; Inflammation; Neoplasms; Radiotherapy

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Labeling; Drug Prescriptions; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Europe; Hematinics; Humans; Neoplasms; Recombinant Proteins; United States; United States Food and Drug Administration

Physiopathology of anaemia and thrombocytopaenia in children with malignancy: the role of erythropoietin and thrombopoietin. The aim of our work was to determine the role of an impaired erythropoietin (EPO) and thrombopoietin (TPO) production in development of, respectively, the anaemia and thrombocytopaenia in children with malignancy. Simultaneous dosage of EPO and of serum transferrin receptor have shown that anaemia in these patients is of central origin but related to a blunted EPO production. The same observation has been made in children at diagnosis either with acute leukaemia or solid tumour as well as during chemotherapy. In patients under maintenance chemotherapy for acute leukaemia, using long-term bone marrow cultures, we could detect an impaired supportive capacity of bone marrow micro-environment for erythropoiesis. The last part of this work has shown that thrombocytopaenia associated with acute leukaemia in children is accompanied by very high TPO levels as observed in other thrombocytopaenia of central origin, excepted in patients with acute leukaemia of myeloid origin. In these patients, TPO levels are inappropriately low in most cases. The low TPO levels are related to the presence of TPO receptor-expressing myeloid leukaemic cells, suggesting that TPO is "consumed" by blast cells expressing a functional TPO receptor.

Topics: Anemia; Child; Erythropoietin; Humans; Neoplasms; Thrombocytopenia; Thrombopoietin

Topics: Anemia; Austria; Erythropoietin; Hematinics; Humans; Neoplasms; Practice Guidelines as Topic; Recombinant Proteins

A group of 62 patients with different advanced cancers and with an anaemic condition were treated with a short course of darbepoetin administered on two different schedules as supportive therapy. The response rates (i.e. a haemoglobin increase of at least 1 g in 1 month) were 45.7% overall, 52.3% with weekly administration and 39% with 3-weekly administration. Darbepoetin activity was higher in men than in women, in younger patients than in older patients and in moderately anaemic patients than in severely anaemic patients, but these differences were not significant. Darbepoetin administration appears to be useful in rapidly reversing anaemia related to advanced cancer. However, the results reported in the literature for alpha-erythropoietin remain more appealing.

Topics: Aged; Anemia; Darbepoetin alfa; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Treatment Outcome

The treatment of chemotherapy associated anemia in patients with cancer has varied greatly in recent years. The objective of this study was to verify whether the most frequently used therapeutic schedules of erythropoietin administration demonstrate equivalent effectiveness.. Treatments corresponding to 1,103 patients with cancer receiving treatment with erythropoietic colony-stimulating factors from January 2003 to April 2006 were reviewed. After applying a selection algorithm, 170 cases were analysed: 55 treated with epoetin alpha 10,000 IU 3 times per week, 63 receiving darbepoetin alpha 150 microg weekly and 52 treated with darbepoetin alpha 500 microg every 3 weeks. The main variables used to compare effectiveness were the increase in serum hemoglobin levels during treatment and the percentage of patients with hemoglobin values > or = 120 g/l.. The differences in maximum hemoglobin values achieved at baseline and during the study period, and those between the final and baseline hemoglobin values were similar in the 3 groups. The percentage of patients with hemoglobin values > or = 120 g/l during and at the end of treatment was equivalent for the group receiving epoetin alpha 10,000 IU three times per week and darbepoetin alpha 150 microg per week. However this parameter war inferior for the group treated with darbepoetin alpha 500 microg every 3 weeks.. Epoetin alpha 10,000 IU 3 times per week was found to be as effective as darbepoetin alpha 150 microg per week in all the studied parameters, while darbepoetin alpha 500 microg every 3 weeks was not in one of them.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Retrospective Studies

Topics: Animals; Clinical Trials as Topic; Disease Progression; Erythrocyte Transfusion; Erythropoietin; Hemoglobinometry; Humans; Mice; Neoplasms; Oxygen; Practice Guidelines as Topic; Risk Factors

Topics: Antibodies, Monoclonal; Biomedical Research; Biotechnology; Drug Industry; Erythropoietin; Humans; Inflammation; Insulin; Neoplasms; Pharmaceutical Preparations; Time Factors; United States

Over 10 years after their approval as cancer supportive and palliative care agents, erythropoietin and the bisphosphonates began to show unexpected, serious adverse events, which resulted in dramatic changes in how they were subsequently prescribed to cancer patients.. The purpose of this opinion piece is to reexamine what happened.. We relied on the published literature as well as the investigators' own experience and preliminary data.. The importance of adverse event reporting in cancer supportive and palliative agents should go beyond that which is mandated by the Food and Drug Administration (FDA). Funding agencies and practicing oncologists should remain vigilant for such adverse events during the testing of new agents and after their approval. They should be willing to report such events without delay.

Topics: Antineoplastic Agents; Diphosphonates; Erythropoietin; Humans; Neoplasms; Palliative Care

Anemia is a common complication in patients with inflammatory diseases of many kinds, including cancer. The mechanisms that have captured the most attention include cytokine-mediated changes in both the production of and the response to erythropoietin (Epo), as well as important alterations in iron metabolism. The last is brought about by the relatively recently recognized peptide hormone, hepcidin. The availability of recombinant human Epo and its derivatives (known by class as Erythropoietic Stimulating Agents, ESAs) has dramatically changed anemia management in patients with cancer but, in the process, has raised as many issues as have been answered. This chapter reviews the mechanisms resulting in anemia in inflammation, including cancer, and focuses on the controversies around management with the ESAs and the adjuvant use of iron in anemia management.

Topics: Anemia; Antimicrobial Cationic Peptides; Cell Line; Erythropoiesis; Erythropoietin; Hepcidins; Humans; Inflammation; Interleukin-1alpha; Interleukin-6; Iron; Neoplasms; Recombinant Proteins; Tumor Necrosis Factor-alpha

Cancer and venous thromboembolism (VTE), VTE and cancer: there is a close bond between these two diseases. On the one hand, a cancer patient runs a high risk of developing VTE. Certain cancer-specific factors, such as its metastatic nature increase this risk. The means involved in the care of cancer (insertion of a venous catheter, chemotherapy, etc.) also increase the probability of a thromboembolism. On the other hand, VTE, especially if it is idiopathic, may be the harbinger of a neoplasm. The present paper involves the dual nature of this relationship, first dealing with several points specific to the occurrence of VTE in a cancer patient, before dealing with the specific care in a curative and prophylactic situation. VTE is then considered as a clinical manifestation prior to a cancer. Several characteristics evoking an underlying neoplasm are known. However, the benefits of the screening for cancer when confronted with an episode of VTE remains to be debated.

Topics: Antineoplastic Agents; Catheterization, Central Venous; Erythropoietin; Humans; Neoplasms; Prognosis; Risk Factors; Venous Thromboembolism

Topics: Anemia; Darbepoetin alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

Topics: Anemia; Darbepoetin alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Risk; Venous Thromboembolism

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Humans; Neoplasms

To conduct a cost-utility analysis on recombinant human erythropoietin (rHuEPO) for treating anemic cancer patients induced by chemotherapy compared to blood transfusion alone under the Thai health care setting.. A health care provider's perspective was used to examine relevant costs and outcomes using the Markov model. Cost data were estimated based on the reference price set by the Ministry of Public Health. The effectiveness data were obtained from a systematic review of published literature. The results were presented in terms of incremental cost-effectiveness ratio (ICER) in Thai Baht per Quality Adjusted Life Years (QALYs) gained. A probabilistic sensitivity analysis method was performed.. The ICERs of rHuEPO compared to blood transfusion alone were 3.7 and 2.7 millions Baht per QALY for patients with hemoglobin less than 8 g/dl and 8-9 g/dl, respectively. The rHuEPO required additional resources (more costly) with less benefit compared to blood transfusion for patients with hemoglobin 9-10 g/dl.. The rHuEPO may be cost-ineffective for the treatment of anemia caused by chemotherapy in cancer patients in Thailand.

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Cost-Benefit Analysis; Erythropoietin; Humans; Markov Chains; Neoplasms; Probability; Quality-Adjusted Life Years; Recombinant Proteins; Thailand

To update the American Society of Clinical Oncology/American Society of Hematology (ASCO/ASH) recommendations for the use of epoetin. The guideline was expanded to address use of darbepoetin and thromboembolic risk associated with these agents.. An Update Committee ("Committee") reviewed and analyzed data published since 2002 through July 2007. MEDLINE and the Cochrane Collaboration Library databases were searched.. For patients with chemotherapy-associated anemia, the Committee continues to recommend initiating an erythropoiesis-stimulating agent (ESA) as hemoglobin (Hb) approaches, or falls below, 10 g/dL, to increase Hb and decrease transfusions. ESA treatment continues to be recommended for patients with low-risk myelodysplasia for similar reasons. There is no evidence showing increased survival as a result of ESA treatment. Conclusive evidence is lacking that, absent clinical circumstances necessitating earlier treatment, initiating ESAs at Hb levels greater than 10 g/dL either spares more patients from transfusion or substantially improves their quality of life. Starting doses and dose modifications based on response or lack thereof should follow the package insert. Continuing ESAs beyond 6 to 8 weeks in the absence of response, assuming appropriate dose increase has been attempted in nonresponders as per US Food and Drug Administration-approved labeling, does not seem to be beneficial, and ESA therapy should be discontinued. The Committee recommends monitoring iron stores and supplementing iron intake for ESA-treated patients. ESAs should be used cautiously with chemotherapy, or in clinical states, associated with elevated risk for thromboembolic complications. The Committee also cautions against ESA use for patients with cancer who are not receiving chemotherapy, since recent trials report increased thromboembolic risks and decreased survival under these circumstances.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Evidence-Based Medicine; Hematinics; Humans; Neoplasms; Recombinant Proteins; Societies, Medical

Erythropoietin (Epo) therapy reduces red cell transfusion requirements and improves the quality of life of anemic cancer patients receiving chemotherapy. However, there is concern that Epo may promote tumor growth. We investigated by real-time RT-PCR, immunofluorescence microscopy, Western blotting and cell growth analysis whether human cancer cell lines (SH-SY5Y, MCF7, HepG2, U2-OS, HeLa, HEK293T, RCC4, HCT116, 7860wt and SW480) possess functional Epo receptors (EpoR). We detected EpoR mRNA in all cell lines. Neither hypoxia nor Epo treatment altered the level of EpoR mRNA expression. Four commonly used commercial antibodies proved to be unsuitable for immunoblot procedures because they cross-reacted with several proteins unrelated with EpoR. Depending on the antibody used, EpoR was localized to the plasma membrane, the cytoplasm or the nucleus. Experiments with small interfering RNA showed that EpoR protein was not expressed by the tumor cells except by UT7/Epo leukemia cells, which served as an EpoR positive control line, and by cells transfected with the human EpoR gene. Apart from UT7/Epo, none of the tumor cell lines responded to Epo treatment with phosphorylation of signaling molecules or with cell proliferation.

Topics: Antibodies; Blotting, Western; Cell Hypoxia; Cell Line, Tumor; Cell Proliferation; Cross Reactions; Erythropoietin; Fluorescent Antibody Technique; Gene Expression; Humans; Immunohistochemistry; Neoplasms; Phosphorylation; Receptors, Erythropoietin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; Transfection

Erythropoietin (Epo) receptor (EpoR) is expressed in several cancer cell lines, and the functional consequence of this expression is under extensive study. In this study, we used a cervical cancer cell line in which EpoR was first found to be expressed and to correlate with the severity of the disease. We demonstrate that Epo is a chemoattractant for these cancer cells, enhancing their migration under serum-starved conditions. Using a Transwell migration system, we show that Epo enhances cancer cell migration in a dose- and time-dependent manner. The effect of Epo is dependent on the activity of two signaling pathways: the mitogen-activated protein kinase (MAPK) pathway and the RhoA GTPase pathway. We show that Epo activates both pathways in a Janus kinase-dependent manner and that this activation is required for Epo effects on cell migration. Furthermore, we use both pharmacological and genetic inhibitors to demonstrate that the activation of RhoA GTPase is dependent on the activity of the MAPK pathway, providing the first evidence for interaction between these two signaling cascades.

Topics: Cell Movement; Enzyme Activation; Erythropoietin; Extracellular Signal-Regulated MAP Kinases; HeLa Cells; Humans; Mitogen-Activated Protein Kinases; Neoplasms; rhoA GTP-Binding Protein; Signal Transduction

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Erythropoietin; Hematinics; Humans; Neoplasms

Topics: Anemia; Disease Progression; Erythropoietin; Humans; Neoplasms

Previous labeling and guidelines recommended initiating erythropoiesis agents (ESAs) for chemotherapy-induced anemia (CIA) at hemoglobin (Hb) levels < 11 g/dL, maintaining near 12 g/dL, and withholding at > or = 13 g/dL. This study analyzed adherence with recommendations in administration of darbepoetin (DA) to cancer patients.. Retrospective analysis of Hb levels at which DA was administered using Varian electronic medical records (EMRs). The dataset comprises 141 694 cancer patients from 82 sites across 13 states. The study evaluated DA administrations with respect to recorded Hb for 8988 patients from 1/1/05 to 5/31/07.. Proportion of DA administrations at Hb > or = 12 and Hb > or = 13 g/dL. Hb level was analyzed for all administrations, stratified by year and anemia type (CIA, anemia-of-cancer, and myelodysplastic syndrome).. There were 51 111 DA administrations with Hb results. The proportion of administrations at Hb > or = 12 g/dL was 7.2% and at Hb > or = 13 g/dL was 0.6%, and for CIA 6.9%/0.6%, anemia of cancer (AOC) 8.8%/0.8%, and myelodysplastic syndrome (MDS) 6.5%/0.6%. The proportion of all DA administrations at Hb > or = 12 g/dL and > or = 13 g/dL declined from 8.6% to 5.3% (p < 0.0001) and from 0.7% to 0.4% (p < 0.0007), respectively during 1/1/05-5/31/07.. In this population, DA administration at Hb > or = 12 g/dL and Hb > or = 13 g/dL occurred in 7.2% and 0.6% of administrations, respectively, a approximately 93% adherence rate with recommendations. Further research is required to understand dose titrations at Hb 12-13 g/dL, and whether similar patterns are observed for other ESAs, and in other practice settings. This study provides context for the debate regarding the utilization, benefits and risks of ESAs in cancer patients.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Darbepoetin alfa; Drug Utilization; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Practice Patterns, Physicians'; Retrospective Studies

To report the design, methodology, implementation and initial results of the Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (DOSE) Registry, the first US patient registry to collect and report on practice patterns and outcomes associated with erythropoiesis-stimulating therapy (EST) for anaemia management in oncology patients.. DOSE is a prospective ongoing registry of oncology patients treated with epoetin-alpha or darbepoetin-alpha. Patients from either community or academic centres who meet prespecified entry criteria are eligible for inclusion in the registry. Data collected include patient demographic and clinical characteristics, EST administration, haematological parameters, patient-reported outcomes and medical resource utilization. Patients are followed from EST initiation through to the end of therapy or 16 weeks, whichever is earlier.. Initial results from 45 sites for 861 patients (epoetin-alpha, n = 312; darbepoetin-alpha, n = 549) showed that baseline demographic and disease characteristics were similar between the two treatment groups. Administration of EST at both weekly and > or =2-weekly intervals was observed in both groups, with similar numbers of haemoglobin determinations. However, the mean number of office visits was higher in the darbepoetin-alpha group despite more frequent administration of therapy at > or =2-weekly intervals in this group. Mean treatment duration was approximately 8 weeks for both groups. Mean post-baseline haemoglobin levels of 11-12 g/dL were achieved and maintained at all timepoints assessed with epoetin-alpha but not with darbepoetin-alpha. Both groups had similar rates of packed red blood cell transfusions.. The DOSE Registry is a valuable source of data relating to anaemia management, practice patterns and outcomes in oncology patients from the perspective of actual clinical practice. Results from this registry should provide patients, clinicians and healthcare decision makers with a better understanding of the relationship between EST dosage and outcomes in the clinical setting.

Topics: Aged; Anemia; Darbepoetin alfa; Databases, Factual; Epoetin Alfa; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Internet; Iron; Male; Middle Aged; Neoplasms; Prospective Studies; Recombinant Proteins; Registries; Treatment Outcome; United States

Topics: Anemia; Decision Making; Erythropoietin; Health Care Rationing; Hematinics; Humans; Insurance, Health, Reimbursement; Neoplasms; Patient Selection; Practice Guidelines as Topic; Practice Patterns, Physicians'; Recombinant Proteins; United States

Topics: Anemia; Erythropoiesis; Erythropoietin; History, 19th Century; History, 20th Century; Humans; Hypoxia; Neoplasms; Recombinant Proteins; Uremia

Patients with cancer may receive erythropoiesis-stimulating agents (ESAs), including darbepoetin alfa (DA) or epoetin alfa (EA), to treat cancer-related anemia (CRA). DA and EA differ, however, with respect to their assumed duration of effect and thus their approved frequency of dosing, complicating direct comparison of their doses and costs.. The objective of this study was to examine, from the perspective of a third-party payer, patterns of use and costs of DA and EA in patients with CRA, using episode-based methodology to account for differences in assumed duration of effect and frequency of dosing with these products.. Using a large US health insurance claims database, we identified all patients with cancer who received ESAs between January 1, 2005, and June 30, 2005 (study period). For each such patient, we identified all unique episodes of care (EOCs) with DA or EA, and then compared mean weekly dose and cost of ESA therapy within these EOCs, which were calculated using the ratio of total dose received and total cost of ESA therapy, respectively, to total EOC duration; only the first EOC for each patient was considered. EOCs were assumed to begin on the date of first ESA administration within the study period, and end on the date of final ESA administration (within the episode) plus an assumed duration of effect based on the ESA received and corresponding dose. We also estimated the ratio of mean weekly dose of EA (in units) to mean weekly dose of DA (in micrograms) (EA/DA weekly dose ratio). Multivariate regression was used to control for differences in baseline characteristics of EA and DA patients.. We identified a total of 1226 patients with complete EOCs with ESAs (EA, 381; DA, 845). DA patients were more likely to have had evidence of receipt of chemotherapy (54% vs 47% for EA; P = 0.02); they also had more comorbidities (mean Charlson comorbidity scores, 4.3 and 3.9, respectively; P < 0.01). Estimated mean (95% CI) weekly dose within EOCs was 97 microg (94-99) for DA, and 43,184 U (40,181-46,589) for EA; EA/DA weekly dose ratio was 445:1. Adjustment for differences in patient characteristics yielded a slightly lower ratio (403:1). Results were sensitive to the exclusion of EOCs consisting of a single administration of ESA therapy and/or the addition of an assumed duration of effect to the final ESA dose administered.. Cost comparisons of DA and EA are sensitive to the assumed duration of effect added to the final dose of ESA therapy, especially for EOCs with relatively few administrations.

Topics: Adolescent; Adult; Aged; Anemia; Comorbidity; Darbepoetin alfa; Databases, Factual; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; United States

Topics: Anemia; Erythropoietin; Humans; Neoplasms; United States; United States Food and Drug Administration

Topics: Anemia, Hypochromic; Antineoplastic Combined Chemotherapy Protocols; Erythropoiesis; Erythropoietin; Female; Humans; Male; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Sensitivity and Specificity; Survival Analysis; Treatment Outcome

Topics: Anemia; Erythropoietin; Humans; Incidence; Iron; Neoplasms; Prevalence; Time Factors

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Hemoglobins; Humans; Neoplasms; Recombinant Proteins; Risk Assessment; Thromboembolism

Anemia is frequently experienced by cancer patients receiving chemotherapy and can negatively impact the patient's prognosis. Blood transfusions, iron supplementation (in absolute or functionally iron-deficient anemias), and erythropoiesis-stimulating agents (ESAs) are among the treatment options for anemia. Treatment options for anemia management should be selected based on the best benefit-to-risk ratio for each individual patient. In September 2007, the working party of the European Organization for Research and Treatment of Cancer (EORTC) updated their guidelines on the use of ESAs, which are summarized in this paper. ESAs reduce the number of transfusions required and significantly improve quality of life in patients with chemotherapy-induced anemia. A sustained hemoglobin level of about 12 g/dl should be the target for treatment with ESAs. ESAs should be used according to the EORTC guidelines and within label with carefully considered exceptions.

Topics: Anemia; Antineoplastic Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Practice Guidelines as Topic; Recombinant Proteins

Topics: Anemia; Erythropoietin; Hematinics; Humans; Legislation, Drug; Neoplasms; United States; United States Food and Drug Administration

Darbepoetin alfa is an erythropoeisis-stimulating agent that can be given in an every week (QW) or every-3-weeks (Q3W) schedule for the treatment of chemotherapy-induced anemia. We assessed the cost-effectiveness of Q3W darbepoetin alfa compared to QW darbepoetin alfa, from both a health-care and societal perspective in France. Based on a clinical trial design, a decision-tree model with a 16-week time horizon was developed in Excel(R). A probabilistic sensitivity analysis was carried out. The Q3W regimen resulted in lower total costs per patient from the health-care (-180 euro [95 % CI = -461.2;74]) and societal (-243 euro [95 % CI = -588;62]) perspective. Probabilistic sensitivity analysis showed an incremental cost-effectiveness ratio in favor of Q3W treatment from both perspectives. The Q3W schedule is cost saving compare to the QW schedule. It also reduces the burden of the frequent visits for the patients.

Topics: Anemia; Antineoplastic Agents; Clinical Trials, Phase III as Topic; Confidence Intervals; Cost-Benefit Analysis; Darbepoetin alfa; Drug Administration Schedule; Drug Costs; Erythropoietin; France; Hematinics; Humans; Models, Economic; Neoplasms; Randomized Controlled Trials as Topic

Epoetin alpha is known to produce a hematological response in anemic cancer patients. A concomitant reduction in fatigue as well as an improvement of depression and anxiety and of quality of life has been reported. However, these effects are discussed controversially. Psychological variables may have a moderating effect on fatigue reduction.. Fifty-four anemic cancer outpatients were treated with epoetin alpha over 26 weeks with an initial dose of 3 x 10,000 IU/week and further individually adapted dosage. Hemoglobin level, fatigue, depression, anxiety, and health-related quality of life were measured every 4 weeks.. The hematological response rate was 50%, with 1/3 occurring after more than 8 weeks of treatment. Fatigue, depression, and quality of life improved significantly. Reduction in fatigue was associated with response, but the correlations between fatigue and hemoglobin were weak. Less depression and higher quality of life before treatment correlated with a better fatigue reduction when controlling for hemoglobin increase and initial fatigue level.. Psychological variables influence the reduction of fatigue during therapy with epoetin alpha in anemic cancer patients and should therefore be assessed at the beginning of treatment.

Topics: Adult; Aged; Anemia; Anxiety; Biomarkers; Case-Control Studies; Depression; Epoetin Alfa; Erythropoietin; Fatigue; Female; Germany; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Predictive Value of Tests; Psychology; Quality of Life; Recombinant Proteins; Surveys and Questionnaires; Time Factors; Treatment Outcome

The stability and transcriptional activity of the hypoxia-inducible factors (HIFs) are regulated by two oxygen-dependent events that are catalyzed by three HIF prolyl 4-hydroxylases (HIF-P4Hs) and one HIF asparaginyl hydroxylase (FIH). We have studied possible links between metabolic pathways and HIF hydroxylases by analyzing the abilities of citric acid cycle intermediates to inhibit purified human HIF-P4Hs and FIH. Fumarate and succinate were identified as in vitro inhibitors of all three HIF-P4Hs, fumarate having K(i) values of 50-80 microM and succinate 350-460 microM, whereas neither inhibited FIH. Oxaloacetate was an additional inhibitor of all three HIF-P4Hs with K(i) values of 400-1000 microM and citrate of HIF-P4H-3, citrate being the most effective inhibitor of FIH with a K(i) of 110 microM. Culturing of cells with fumarate diethyl or dimethyl ester, or a high concentration of monoethyl ester, stabilized HIF-1alpha and increased production of vascular endothelial growth factor and erythropoietin. Similar, although much smaller, changes were found in cultured fibroblasts from a patient with fumarate hydratase (FH) deficiency and upon silencing FH using small interfering RNA. No such effects were seen upon culturing of cells with succinate diethyl or dimethyl ester. As FIH was not inhibited by fumarate, our data indicate that the transcriptional activity of HIF is quite high even when binding of the coactivator p300 is prevented. Our data also support recent suggestions that the increased fumarate and succinate levels present in the FH and succinate dehydrogenase-deficient tumors, respectively, can inhibit the HIF-P4Hs with consequent stabilization of HIF-alphas and effects on tumor pathology.

Topics: Cell Line; Citric Acid Cycle; Dose-Response Relationship, Drug; Enzyme Inhibitors; Erythropoietin; Fibroblasts; Fumarate Hydratase; Gene Expression Regulation, Enzymologic; Hypoxia-Inducible Factor 1, alpha Subunit; Mixed Function Oxygenases; Neoplasms; p300-CBP Transcription Factors; Procollagen-Proline Dioxygenase; Succinate Dehydrogenase; Transcription, Genetic; Vascular Endothelial Growth Factor A

The expression of the hypoxia-inducible protein erythropoietin in tumour cells correlates with levels of tumour hypoxia. Our aim was to look for an interrelation of directly measured oxygenation levels, the presence of tissue erythropoietin and its receptor. Data of tumour oxygenation status, plasma and tissue erythropoietin and its receptor in a group of spontaneously occurring tumours in 15 dogs were collected. Polarographic tumour oxygen partial pressure measurements were obtained and data were correlated. Significant positive correlations were found between tissue erythropoietin and the percentages of pO2 values < or = 10 mmHg. Multivariate analysis revealed no parameters influencing plasma erythropoietin levels. Our results show that a co-expression of erythropoietin receptor and its ligand in spontaneous canine tumours exists, that the level of hypoxia in tumour cells correlates with the level of tissue erythropoietin and suggest the need to be quantitatively and functionally tested as novel prognostic biological parameters in neoplastic tissues.

Topics: Animals; Cell Hypoxia; Dog Diseases; Dogs; Erythropoietin; Neoplasms; Oxygen; Receptors, Erythropoietin

To assess patient preferences across two attributes--effectiveness and convenience--in the selection of an erythropoietic agent to treat chemotherapy-related anemia.. During 2004, 500 adults with solid tumors and anemia were recruited through 50 oncologists' offices across the USA. Data were collected through self-administered questionnaires, divided into two parts. The first, completed by the provider, captured clinical information and providers' perceptions of patient preferences. The second, completed by the patient, recorded knowledge, experiences, and preferences regarding anemia and its treatments. Patient preferences, the relative importance of effectiveness (time to noticeable relief of fatigue) and convenience (number of provider visits required in an 8-week period), were measured using a choice-based conjoint (CBC) analysis. Each attribute was assessed at three levels (4, 6, or 8 weeks/visits).. 467 providers (93%) and 438 patients (88%) completed the preference sections. When choosing a medication to treat anemia, 77% of providers viewed effectiveness as more important to patients than convenience. Similarly, patients had a greater preference for effectiveness than convenience. Relative preference weights were significantly higher for 4- versus 6-week effectiveness (0.61 vs. 0.09, p < 0.001) and 6- versus 8-week effectiveness (0.09 vs. -0.70, p = 0.004). Overall, time to effectiveness was twice as important to patients as the number of visits.. Only two attributes were included in the CBC, which did not control for bias from respondent characteristics or experiences.. When evaluating an erythropoietic agent to treat chemotherapy-related anemia, both providers and patients view effectiveness as more important than convenience.

Topics: Anemia; Chi-Square Distribution; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Patient Satisfaction; Surveys and Questionnaires; Treatment Outcome; United States

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Research Design; Risk Assessment; Treatment Outcome

Topics: Anemia; Erythropoietin; Humans; Neoplasms; Survival Analysis

Topics: Anemia; Clinical Trials as Topic; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Safety; Survival Analysis

The correlation of erythropoietin (EPO) receptor levels with angiogenesis and progression in some cancers has suggested that EPO could acts directly as an angiogenic factor. The purpose of this study was to assess the effect of treatment with human recombinant erythropoietic (rHuEPO) agents in cancer patients with chemotherapy-induced anaemia on endoglin and vascular endothelial growth factor (VEGF) circulating levels as a possible marker of angiogenesis. Endoglin and VEGF were measured in serum samples from 25 cancer patients with chemotherapy-induced anemia before and after 3-4 weeks of treatment with rHuEPO. A group of 28 healthy voluntaries was used as control. VEGF serum levels were significantly higher in cancer patients than in controls. For endoglin, higher levels were observed without reaching statistical significance. No statistically significant differences in endoglin and VEGF serum levels were found between samples obtained before and after treatment with rHuEPO agents. In conclusion, our result do not support that rHuEpo treatment in anaemic cancer patients induce angiogenesis.

Topics: Adult; Aged; Anemia; Antigens, CD; Antineoplastic Agents; Endoglin; Erythropoiesis; Erythropoietin; Female; Humans; Middle Aged; Neoplasms; Neovascularization, Pathologic; Prospective Studies; Receptors, Cell Surface; Recombinant Proteins; Vascular Endothelial Growth Factor A

Topics: Anemia; Clinical Trials as Topic; Erythropoietin; Humans; Kidney Diseases; Neoplasms; Premedication; Preoperative Care

Topics: Anemia; Blood Transfusion; Economics, Pharmaceutical; Erythropoietin; Humans; Iron; Neoplasms; Quality of Life; Treatment Outcome

Erythropoietin (EPO) is a glycoprotein hormone produced by renal tissue in response to hypoxia; EPO functions as a cytokine to precursor cells produced by the bone marrow, stimulating red blood cell production. Erythropoiesis stimulating agents (ESAs) are manufactured molecules designed to mimic the ability of endogenous EPO to bind to EPO receptors and increase red blood cell production. To achieve desired dosing schedules and avoid the need for blood transfusions, oncologists have become increasingly reliant on ESAs to counter the anemia often experienced during chemotherapy. In recent years, significant concerns have been raised about the safety of ESAs, including the possibility of increased cardiovascular events and even increased tumor growth and accelerated mortality in cancer patients. ESAs also contribute significantly to the expense of chemotherapy, rendering them unavailable to some patients and available to others only upon achieving insurance-mandated levels of anemia. A recently discovered "normobaric oxygen paradox" demonstrates that renal tissue can be stimulated to increase EPO production via a simple pattern of oxygen breathing at normal atmospheric pressures. This leads directly to the hypothesis that oxygen breathing may provide chemotherapy patients with a convenient and inexpensive alternative to ESAs. Stimulating endogenous EPO production eliminates the small risk of immune system reaction associated with ESAs. Further, the endogenous physiological EPO doses provided by this method may be safer, in terms of cancer mortality, than the exogenous pharmacological doses inherent in ESA administration. A single patient test case is presented to support the hypothesis that normobaric oxygen breathing can be an effective replacement for ESAs in treating chemotherapy-induced anemia. In this case, a stage III breast cancer patient undergoing dose-dense AC+T chemotherapy obtained a clear response equivalent to ESA treatment by using a pattern of simple oxygen breathing.

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Female; Humans; Medical Oncology; Models, Economic; Models, Theoretical; Neoplasms; Oxygen; Oxygen Inhalation Therapy; Respiration

There is a growing interest in the non-erythropoietic, tissue-protective and restorative actions of erythropoietin (EPO). While studies in this field have indicated that EPO can ameliorate chemotherapy-induced peripheral neuropathy and cardiotoxicity, the issue whether EPO can positively or negatively affect cancer patients is a hot one. In this debate, many activities of EPO are being considered, including tissue/neuroprotection, angiogenesis, anti-inflammatory activity, growth promotion, and inhibition of apoptosis. However, few studies have explored the interactions of EPO with the immune system. A study in this issue of the European Journal of Immunology by Katz et al. adds one new piece to the puzzle by showing that EPO can stimulate B cell-mediated immunity.

Topics: Animals; Antibody Formation; Erythropoietin; Humans; Lymphocytes; Mice; Multiple Myeloma; Neoplasms

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Humans; Iron; Neoplasms; Recombinant Proteins

Topics: Drug Approval; Erythropoietin; Humans; Neoplasms; Risk Assessment; United States; United States Food and Drug Administration

Topics: Anemia; Chronic Disease; Erythropoietin; Hematinics; Humans; Kidney Diseases; Legislation, Drug; Neoplasms; Recombinant Proteins; United States; United States Food and Drug Administration

Topics: Erythropoietin; Humans; Neoplasms; Receptors, Erythropoietin

Topics: Advisory Committees; Anemia; Darbepoetin alfa; Drug and Narcotic Control; Drug Labeling; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Risk; Stimulation, Chemical; Thromboembolism; United States; United States Food and Drug Administration

Topics: Advisory Committees; Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Health Expenditures; Hematinics; Humans; Insurance Coverage; Medicare; Neoplasms; Recombinant Proteins; United States; United States Food and Drug Administration

The aim of this study is to evaluate the endogenous erythropoietin production in cancer patients with anemia.. Our prospective study interested 99 cancer patients with anemia from 17 to 80 years old, during the period going from March 2002 to December 2004, and 31 healthy individuals with anemia caused by iron deficiency. A blood sample was collected from each patient, as well as healthy individuals to measure serum erythropoietin, C reactive protein and ferritin.. The increase of serum erythropoietin was significantly lower in patients than in healthy individuals (P < 0.05). 25.2% of our cancer patients have inflammatory anemia and 74.7% presented microcytic anemia associated with increase of serum ferririn and CRP. These values were significantly higher than in healthy individuals (p < 0.05).. Anemia in cancer patients results from activation of inflammatory system, which inhibit erythropoietin production. Apart from etiologic treatments, anemia can be treated with recombinant human erythropoietin.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Case-Control Studies; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Prospective Studies

Topics: Anemia; Centers for Medicare and Medicaid Services, U.S.; Conflict of Interest; Darbepoetin alfa; Drug Industry; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Medical Oncology; Medicare; Neoplasms; Nephrology; Product Surveillance, Postmarketing; Recombinant Proteins; United States; United States Food and Drug Administration

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Health Resources; Hematinics; Humans; Injections; Neoplasms; Recombinant Proteins; Research Design; Time Factors; Treatment Outcome

The inpatient dosing patterns and treatment costs in cancer and predialysis chronic kidney disease (CKD) patients treated with erythropoietic agents from a hospital pharmacy perspective were studied.. An analysis of electronic inpatient records from the Premier Perspective comparative hospital database was conducted. Study participants were identified through hospitalizations recorded between July 2002 and March 2005 from over 500 hospitals nationwide. Adult patients with an admitting diagnosis of cancer or predialysis CKD and treated with epoetin alfa or darbepoetin alfa during hospitalization were included. Patients who had received renal dialysis or both agents during a hospitalization were excluded. Wholesale acquisition costs from September 2006 were used to calculate drug costs.. A total of 25,645 hospitalized patients with cancer (22,873 received epoetin alfa; 2,772 received darbepoetin alfa) and 66,822 hospitalized patients with CKD (60,079 received epoetin alfa; 6,743 received darbepoetin alfa) were identified. The mean cumulative dose per hospitalization resulted in dose ratios of 245:1 and 242:1 (units epoetin alfa:micrograms darbepoetin alfa) for cancer and CKD patients, respectively. On the basis of the cumulative dose per hospitalization, drug costs for darbepoetin alfa-treated patients were approximately 50% higher than drug costs for epoetin alfa-treated patients for both oncology and CKD patients.. Epoetin alfa was associated with less cost compared with darbepoetin alfa for treating inpatients with cancer or CKD. Further research including the patients' clinical outcomes is necessary to determine the true pharmacoeconomic differences between the two agents.

Topics: Adult; Aged; Anemia; Cohort Studies; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Health Care Costs; Humans; Inpatients; Kidney Diseases; Male; Middle Aged; Neoplasms; Pharmacy Service, Hospital; Recombinant Proteins; Retrospective Studies

Topics: Anemia; Combined Modality Therapy; Drug Administration Schedule; Drug Monitoring; Erythropoietin; Hematinics; Humans; Neoplasms; Nurse's Role; Practice Guidelines as Topic; Recombinant Proteins; Safety Management

Approximately 60% of anaemic cancer patients respond to epoetin treatment. An early marker of response would be valuable in order to avoid ineffective treatment. We have previously shown that beta globin mRNA increases rapidly after epoetin beta treatment of healthy controls. In the present study we have evaluated whether a change of this marker during the first 2 weeks of epoetin treatment could predict later Hb response in anaemic cancer patients. Twenty cancer patients with Hb <11 g/dl received epoetin beta (NeoRecormon) 10,000 IU three times weekly during 6 weeks. Hb, reticulocytes and beta-globin mRNA were followed. The latter was measured quantitatively using PCR via the 5' nuclease assay. Eleven patients responded with a Hb increase of >1 g/dl, nine were nonresponders. All responders increased in beta-globin mRNA within 2 weeks, mean 7.7 x base-line. With a cut-off of an increase of 3 x base-line value, we obtained a specificity of 45% and a sensitivity of 91% for the prediction of a later increase of Hb >1 g/dl. With a cut-off of 4x base-line, the specificity increased to 66%, but the sensitivity decreased to 82%. Beta globin mRNA increases before Hb in all responding patients. However, some non-responding patients also show an increase, and there is a trade-off between specificity and sensitivity as the cut-off level is set at different levels. Compared to reticulocyte count, beta-globin mRNA is more reliable in the individual patient, but the clinical usefulness of the assay needs to be evaluated in further studies.

Topics: Anemia; Beta-Globulins; Biomarkers; Cell Count; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Recombinant Proteins; Reticulocytes; RNA, Messenger; Sensitivity and Specificity; Treatment Outcome

Topics: Erythropoietin; Guidelines as Topic; Humans; Neoplasms; Retrospective Studies

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

Topics: Anemia; Blood Platelets; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Neovascularization, Pathologic; Receptors, Erythropoietin; Thromboembolism

To explore impaired erythropoiesis and relative inadequacy of erythropoietin production in the anemic cancer patients and the correlation of tumor necrosis factor-alpha (TNF-alpha) or interferon-gamma (IFN-gamma) with inadequate erythropoietin (EPO) response and impaired erythropoiesis in cancer patients with anemia.. Fifty adult anemic and 15 non-anemic tumor patients were studied. Serum EPO levels were measured by radioimmunoassay (RIA) and serum soluble transferrin receptor (sTfR). TNF-alpha and IFN-gamma levels by enzyme-linked immunosorbent assay (ELISA). Log transformed EPO and sTfR values were used in statistical analysis. The R correlation analyses were performed.. The mean serum immunoreactive erythropoietin level in anemic cancer patients [(23.11 +/- 10.00) IU/L] was not significantly higher than in healthy people (P = 0.053), but significantly lower than in IDA patients with similar degree of anemia [(43.00 +/- 22.00) IU/L, P < 0.01]. Both O/P EPO [0.88 (0.54-1.10)] and O/P sTfR [0.89 (0.57-1.22)] were significantly lower in anemic cancer patients than in controls and in non-anemic cancer patients. There was no significant difference between the latter two groups. Furthermore, the expected inverse linear relation between serum EPO and hemoglobin levels was absent in the anemic cancer patients, and so did the relation between serum sTfR and hemoglobin levels. There was no correlation between O/P EPO and O/P sTfR. The serum levels of both TNF-alpha and IFN-gamma in anemic cancer patients [(25.75 +/- 26.71) ng/L, (50.49 +/- 42.12) ng/L, respectively] were significantly higher than those in healthy controls (both P < 0.01) or in nonanemic cancer patients (both 0.01 < P < 0.05), and so did between non-anemic cancer patients and controls. The serum levels of TNF-alpha were inversely correlated with hemoglobin levels (r = - 0.40, P = 0.004), O/P EPO (r = -0.32, P = 0.025) or O/P sTfR (r = -0.36, P = 0.01); while serum levels of IFN-gamma were inversely correlated with hemoglobin levels (r = -0.36, P = 0.01) or O/P sTfR (r = 0.39, P = 0.006), but not with O/P EPO. Conclusions Anemia of cancer is due to impaired erythropoiesis and relative inadequacy of EPO production. TNF-alpha might inhibit EPO production and erythropoiesis, while IFN-gamma maybe directly inhibit erythropoiesis and be independent of EPO response inadequacy.

Topics: Adolescent; Adult; Aged; Anemia; Erythropoiesis; Erythropoietin; Female; Humans; Interferon-gamma; Male; Middle Aged; Neoplasms; Receptors, Transferrin; Tumor Necrosis Factor-alpha

Although a significant negative prognostic factor, tumor hypoxia can be exploited for gene therapy. To maximize targeting within the tumor mass, we have developed synthetic gene promoters containing hypoxia-responsive elements (HREs) from the erythropoietin (Epo) gene as well as radiation-responsive CArG elements from the early growth response (Egr) 1 gene. Furthermore, to achieve high and sustained expression of the suicide gene herpes simplex virus thymidine kinase (HSVtk), our gene therapy vectors contain an expression amplification system, or 'molecular switch', based on Cre/loxP recombination. In human glioma and breast adenocarcinoma cells exposed to hypoxia and/or radiation, the HRE/CArG promoter rapidly activated Cre recombinase expression leading to selective and sustained HSVtk synthesis. Killing of transfected tumor cells was measured after incubation with the prodrug ganciclovir (GCV; converted by HSVtk into a cytotoxin). In vitro, higher and more selective GCV-mediated toxicity was achieved with the switch vectors, when compared with the same inducible promoters driving HSVtk expression directly. In tumor xenografts implanted in nude mice, the HRE/CArG-switch induced significant growth delay and tumor eradication. In conclusion, hypoxia- and radiation-activated 'molecular switch' vectors represent a promising strategy for both targeted and effective gene therapy of solid tumors.

Topics: Adenocarcinoma; Adenoviridae; Animals; Antiviral Agents; Brain Neoplasms; Breast Neoplasms; Cell Death; Cell Hypoxia; Combined Modality Therapy; Early Growth Response Protein 1; Erythropoietin; Ganciclovir; Gene Expression Regulation, Neoplastic; Genes, Switch; Genes, Transgenic, Suicide; Genetic Engineering; Genetic Therapy; Genetic Vectors; Glioma; Humans; Mice; Mice, Nude; Neoplasms; Oncolytic Virotherapy; Promoter Regions, Genetic; Simplexvirus; Thymidine Kinase; Tumor Cells, Cultured

Patients with cancer-related anemia have an inadequate Epo response that is further impaired by cancer treatments such as chemotherapy. Significant number of studies have demonstrated that treatment of anemia in cancer patients using recombinant human EPO(rHuEPO, epoetin alfa) significantly increases hemoglobin(Hb) levels,reduces transfusion requirements,and improves quality of life,particularly by relieving fatigue. However,the findings of several studies have raised the possibility of an adverse effect of thromboembolism. The American Society of Clinical Oncology and the American Society of Hematology developed an evidence-based clinical practice guideline for the use of epoetin in patients with cancer. In cancer patients, the risk of bleeding depends not only on the platelet count, but also on the underlying disease, in accordance with coagulation defects. The cause of thrombocytopenia must be established prior to platelet transfusion since platelet transfusions may be relatively contraindicated in certain conditions e. g., heparin-induced thrombocytopenia(HIT), and thrombotic thrombocytopenic purpura/hemolytic uremic syndrome(TTP/HUS).

Topics: Anemia; Disseminated Intravascular Coagulation; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Neoplasms; Platelet Transfusion; Quality of Life; Recombinant Proteins; Thrombocytopenia

An anti-anemia drug may improve self-reported quality of life (QOL) partly because patients know their hemoglobin level is rising. In the absence of any published studies on this topic, the authors investigated the association between knowledge of hemoglobin levels and self-reported QOL.. The study analyzed health-related QOL (HRQOL) data from five randomized clinical trials of erythropoietic therapy in patients with cancer-related anemia. Patients were asked whether they knew their hemoglobin level and, if so, to report its value. Patients (n=1007) were grouped into three categories depending on the extent and accuracy of hemoglobin level knowledge. HRQOL scale scores were compared between categories.. Only 23.2% of patients reported knowing their hemoglobin level at the end of the study; however, the value was accurate (within 1 g/dl) in 88.0% of these patients. On five of the 11 HRQOL scales studied, there was a significant association between knowledge of hemoglobin level and HRQOL score. However, the magnitude of the mean difference between those who knew vs. those who did not know their hemoglobin was generally below scale thresholds for minimally important differences.. Patient knowledge of hemoglobin level has a modest association with some aspects of self-reported HRQOL. The magnitude of this association, where it exists, would be unlikely to explain large group differences in HRQOL reports over time, even for patients who know their hemoglobin level.

Topics: Aged; Anemia; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Fatigue; Female; Health Knowledge, Attitudes, Practice; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Sickness Impact Profile

Inpatient costs associated with different erythropoietic-stimulating therapy regimens have not been compared in an oncology setting.. To conduct a cost analysis of different regimens of epoetin alfa (EPO) and darbepoetin alfa (DARB) in an inpatient oncology setting.. A retrospective evaluation of oncology diagnosis-related group discharges during 2003, in 30 community hospitals, identified EPO treatment patterns. Wholesale acquisition costs were determined for patients who received EPO 40,000 units or more once weekly. Potential differences in costs were calculated using conversion ratios for an equivalent EPO dose 3 times weekly or DARB dose once weekly (EPO:DARB ratio 260:1, approximating DARB 150 microg once weekly). A sensitivity analysis was performed using an EPO:DARB ratio of 400:1, approximating DARB 100 microg once weekly (1.5 microg/kg).. Among the 1410 EPO doses administered (n = 677 pts.), a dose of 40,000 units or more was used 44% of the time (n = 311 pts.), with dosing initiated on average 5.6 days after admission. For these 311 evaluable patients, switching from EPO 40,000 units once weekly to EPO 10,000 units 3 times weekly reduced per-patient and total drug acquisition costs by approximately 50% (704 US dollars vs 359 US dollars and 218,938 US dollars vs 111,615 US dollars, respectively). Relative to EPO once weekly, switching patients to DARB resulted in increased drug acquisition costs at the 260:1 conversion and lower costs at the 400:1 conversion. However, EPO 3 times weekly remained the least costly option by 44-63%. The cost-savings realized with EPO 10,000 units 3 times weekly increased with longer duration of hospitalization.. In an inpatient setting, use of EPO 10,000 units 3 times weekly may minimize expenditures associated with treatment of cancer-related anemia using erythropoietic-stimulating therapies.

Topics: Algorithms; Costs and Cost Analysis; Darbepoetin alfa; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Neutropenia; Recombinant Proteins

Topics: Anemia; Clinical Trials, Phase III as Topic; Drug Administration Schedule; Erythropoietin; Humans; Neoplasms

Cancer patients treated with chemotherapy often develop anaemia. This cross-sectional analysis examined the effect of anaemia treatment on patient and caregiver time and activities.. The analysis included 9,920 patients from 646 US outpatient oncology centres. Patients completed a survey that contained questions about travel time, total time for the visit and other impacts.. The mean time taken for a single clinic visit to receive anaemia treatment was 2.2 h. On average, patients receiving epoetin alfa required 17.6 h more than patients receiving darbepoetin alfa to complete a course of anaemia treatment. All patients in the study reported that they had to adjust at least one activity as a result of clinic visits. Older patients, women and patients from low-income areas were more likely to be accompanied during clinic visits.. Reducing the number of clinic visits needed for anaemia treatment by using darbepoetin alfa may benefit patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Caregivers; Cross-Sectional Studies; Darbepoetin alfa; Employment; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Regression Analysis; Time Factors

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Darbepoetin alfa; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Therapeutic Equivalency

Erythropoietin was the first haematopoietic growth factor to be cloned and put to clinical use in patients with anaemia. In New Zealand, the agent is approved and funded for patients with anaemia secondary to renal failure. Although there is Medsafe approval for its use in various other conditions, including cancer patients, it is not funded by Pharmac for these conditions. There is good evidence that erythropoietin will induce meaningful increases in haemoglobin levels in approximately 60% of cancer patients. Non-responders can be identified within 2-4 weeks of starting therapy and the drug discontinued, thus improving the cost-effectiveness of the programme. Responders have a significant reduction in blood transfusions, have an improved quality of life, and possibly have a better tumour response to chemo-radiotherapy, thus resulting in longer survival. British and American guidelines advocate a significantly greater use of erythropoietin than the very restrictive New Zealand use. Pharmac should review the current evidence as to the benefits of increased erythropoietin usage in New Zealand, and endorse increased access to this agent.

Topics: Anemia; Cost-Benefit Analysis; Drug and Narcotic Control; Erythropoietin; Evidence-Based Medicine; Health Services Accessibility; Humans; National Health Programs; Neoplasms; New Zealand; Treatment Outcome

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

The advent of erythropoiesis-stimulating agents (ESAs) such as recombinant human erythropoietin (rHuEPO) and darbepoetin alfa for the treatment of chemotherapy-induced anaemia was associated with decreased requirements for red blood cell (RBC) transfusions and improved quality of life in cancer patients. Dosing of rHuEPO three times per week is the originally approved regimen, although in some countries weekly dosing is approved in some settings. Darbepoetin alfa was the first ESA to be developed with an extended dosing interval, offering the potential for less frequent administration and greater convenience for patients and healthcare professionals. In a placebo-controlled study of once-weekly darbepoetin alfa treatment in anaemic cancer patients undergoing chemotherapy, significantly fewer treated patients required RBC transfusions, regardless of initial haemoglobin levels. A subsequent dose-finding study of once-every-3-week darbepoetin alfa treatment showed that the drug was effective and well-tolerated in anaemic cancer patients and reduced the need for transfusions at all doses compared with placebo. Timing of ESA administration may be crucial to achieve maximum erythropoietic responses, thus synchronous dosing with 3-weekly chemotherapy cycles may improve efficacy and convenience. Recent trials have shown that synchronous dosing is equally effective, with improved convenience, compared with asynchronous dosing, and that fixed-dose (500 microg) treatment achieves similar efficacy and tolerability as administration by weight.

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Darbepoetin alfa; Drug Administration Schedule; Erythrocyte Transfusion; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Placebos; Quality of Life; Recombinant Proteins

Anaemia has a high prevalence and incidence in patients with cancer receiving chemotherapy and is associated with a range of symptoms, including fatigue, drowsiness, depression, dyspnoea, tachycardia and dizziness. Fatigue, in particular, exerts a considerable impact on patient quality of life, affecting 80-100% of patients receiving chemotherapy and, potentially, delaying treatment. Until recently, red blood cell transfusions were the mainstay of treatment for cancer-related anaemia. While effective in ameliorating symptoms, transfusions are associated with short-lived benefits and a risk of infections and disease transmission. The development of the erythropoiesis-stimulating agent (ESA), recombinant human erythropoietin (rHuEPO), resulted in a 50% reduction in the number of transfusions required in anaemic cancer patients receiving chemotherapy. The subsequently introduced rHuEPO analogue, darbepoetin alfa, stimulates erythropoiesis by the same mechanism as rHuEPO but is associated with a prolonged serum half-life, allowing extended dosing intervals and less frequent administration. With the introduction of a number of ESAs and a growing wealth of data concerning their indications, dosing regimens and safety, European cancer organizations have recently developed guidelines for their effective use in clinical practice.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Administration Schedule; Erythrocyte Transfusion; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Safety

To evaluate epoetin alfa (EPO) treatment of anemia in geriatric cancer patients receiving chemotherapy, a retrospective subgroup analysis was conducted of anemic cancer patients > or =65 years of age from three 16-week community-based studies of thrice-weekly (TIW) or once-weekly (QW) EPO for chemotherapy-related anemia (CRA).. Analyses were conducted on the overall geriatric population (> or =65 years) and by age subgroup (65-74, 75-84, and > or =85 years), and compared with younger patients (<65 years) for each individual study and for pooled data.. Some 3,634 geriatric patients were compared with 3,467 younger patients. From baseline to final measurement, EPO therapy significantly increased Hb by 2.0 g/dl in patients > or =65 years and 1.9 g/dl in patients <65 years (P<0.0001) and reduced transfusion utilization in both groups (P<0.006). Both age groups also had significant improvements in quality of life (QOL), measured by the 100-mm Linear Analog Assessment Scale (LASA). In younger patients, mean LASA changes were significantly greater than those in geriatric patients (P<0.05); however, QOL improvements in both age groups were clinically meaningful. There were no significant differences across geriatric age subgroups or between TIW and QW regimens for Hb change or QOL improvement. Overall hematopoietic response rate to EPO was 65.4% for patients > or =65 years and 64.7% for patients <65 years. Predictors of greater hematopoietic response (based on a pooled analysis) included lower body weight, baseline Hb, and baseline serum erythropoietin levels; better tumor response; and history of EPO dose reduction and longer time on study.. Anemic geriatric patients receiving EPO for CRA responded comparably to younger patients <65 years and should be treated similarly.

Topics: Aged; Aged, 80 and over; Anemia; Blood Transfusion; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins; Retrospective Studies

Anaemia is a common side-effect of malignancy and cancer therapy. Both red cells and erythropoietin will improve anaemia; however, the scarcity and risks of allogeneic blood transfusion need to be carefully considered against the expense and benefits of recombinant human erythropoietin. Both treatment options have significant economic implications and the definitive evaluation from NICE must be awaited with much interest.

Topics: Anemia; Cost-Benefit Analysis; Erythrocyte Transfusion; Erythropoietin; Humans; Neoplasms

Topics: Anemia; Delayed-Action Preparations; Disease Progression; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Humans; Neoplasms; Neutropenia; Patient Selection

Topics: Anemia; Cost-Benefit Analysis; Drug and Narcotic Control; Erythropoietin; Evidence-Based Medicine; Humans; National Health Programs; Neoplasms; New Zealand; Treatment Outcome

Topics: Anemia, Hypochromic; Antineoplastic Agents; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

Cost control is becoming an increasingly important consideration for clinicians when planning how to provide the best treatment for anaemic cancer patients. Administration of erythropoiesis stimulating agents (epoetin alpha, epoetin beta and darbepoetin alpha) has become the standard of care for treatment of anaemia in cancer patients. However, only limited information is available on the economic comparability of epoetin alpha, epoetin beta and darbepoetin alpha, and thus this study was conducted to compare cost per patient of each of these agents for anaemic cancer patients.. All prescriptions of the agents over 1 year were analysed by two Austrian regional public health insurance associations and cost per patient for each agent was calculated from invoicing data. Data from the two regions were combined to obtain total mean drug costs per patient per year.. Analyses showed significantly lower costs for epoetin alpha ( 2,743.27 euros) than for darbepoetin alpha (3,627.98 euros ) or epoetin beta ( 3,292.28 euros): epoetin alpha vs. darbepoetin alpha (P < 0.0001); epoetin beta vs. darbepoetin alpha (P = 0.0001); epoetin alpha vs. epoetin beta (P = 0.0009). As costs of the three agents in Austria are identical for therapeutically equivalent doses, the higher cost of darbepoetin alpha was believed to be due mainly to longer treatment duration to target haemoglobin level.. The finding of a cost difference favouring epoetin alpha over darbepoetin alpha suggests the need for prospective randomized studies comparing efficacy and cost effectiveness of all three agents to obtain more definitive data.

Topics: Aged; Anemia; Austria; Cost Control; Darbepoetin alfa; Economics, Pharmaceutical; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Neoplasms; Recombinant Proteins

To investigate the dosing patterns and treatment costs of erythropoietic agents in adult (>or= 18 years of age) cancer patients newly initiated on epoetin alfa (EPO) or darbepoetin alfa (DARB) in managed care organizations.. An analysis of US medical claims (30 million lives in over 35 health plans) in the period July 1, 2002-February 28, 2005 was conducted. Patients with >or= 1 cancer claim within 90 days prior to initiating EPO or DARB, and who received at least two doses of the same erythropoietic agent, were included in this analysis. Weighted average weekly dosing, cumulative treatment dose, associated drug cost, dosing frequency patterns, and the frequency of outpatient visits were evaluated. The EPO:DARB dose ratio, based on average cumulative treatment doses, was assessed.. 5639 EPO and 2166 DARB patients met the inclusion and exclusion criteria. The EPO group was older (EPO 59.1 years; DARB 57.6 years; p < 0.001) with a higher proportion of men (EPO 38.1%; DARB 33.1%; p < 0.001). Variable dosing frequency was observed with similar treatment durations for the two groups (days: EPO 55.6; DARB 57.7; p = 0.122). A dose ratio of 236:1 was observed (average cumulative dose: EPO 252 856 U; DARB 1072 mcg). Average drug cost was significantly higher in the DARB group (drug cost: EPO 3077 dollars; DARB 4674 dollars; p < 0.001). The average number of hematology/oncology outpatient visits per patient (visits: EPO 7.4; DARB 7.3; p = 0.676) and outpatient visits for hemoglobin determination (visits: EPO 6.7; DARB 6.4; p = 0.093) during treatment was similar between the two groups.. The results were based on medical claims only. The absence of information on actual injection dates in pharmacy claims prevented their incorporation in the analysis.. Based on the average cumulative doses, the EPO:DARB dose ratio was 236:1 (Units EPO: mcg DARB) with 52% greater drug cost in the DARB group. Despite the variable administration frequency observed between the two agents, the number of hematology/oncology outpatient visits was not different.

Topics: Adult; Aged; Cohort Studies; Darbepoetin alfa; Drug Costs; Drug Therapy; Erythropoietin; Female; Humans; Male; Managed Care Programs; Middle Aged; Neoplasms; Office Visits; Outpatients; Physician's Role; Retrospective Studies

Topics: Anemia; Child; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Absorption of a physiological dose of ferrous iron was studied in 18 patients with solid malignancy receiving epoetin therapy for mild chemotherapy-associated anemia. The historical control group consisted of 25 iron replete volunteers (iron absorption 20 +/- 11% in males and 26 +/- 13% in females) and 21 patients with uncomplicated iron deficiency (iron absorption 71 +/- 19%). Iron absorption was increased in the majority of the cancer patients (iron absorption 59 +/- 35%). There were no significant differences in iron absorption between cancer patients who were iron replete or iron deficient according to current clinical practice guidelines (iron deficiency: transferrin saturation < 20% and/or serum ferritin < 100 ng/mL). Red cell iron incorporation was not disturbed in the majority (89%) of patients.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Intestinal Absorption; Iron; Male; Middle Aged; Neoplasms; Organoplatinum Compounds; Recombinant Proteins

To determine the dose-conversion ratio (DCR) between epoetin alfa and darb-epoetin alfa in cancer patients and compare the treatment costs of both agents at the estimated DCRs.. A comprehensive search of the literature was carried out on clinical trials evaluating patients with chemotherapy-related anemia treated with epoetin alfa or darbepoetin alfa. A multivariate meta-analysis regression was conducted to determine the relative doses of these two agents at which they were equally effective. The effectiveness measure used was the area under the hemoglobin change curve. Using the estimated DCR for each dosing regimen, the relative cost of epoetin alfa and darbepoetin alfa treatments in Canada was evaluated.. Twenty-nine study arms, evaluating 12,923 patients (10,582 treated with epoetin alfa and 2341 treated with darbepoetin alfa), were eligible for this study. Results comparing specific dosing regimens indicated that the DCRs were systematically lower than 200:1. The cost premium associated with darbepoetin alfa weekly drug cost was between 37 and 44% above epoetin alfa for the same level of effectiveness.. Based on the evidence from this meta-analysis, epoetin alfa appeared to be more cost-effective compared to darbepoetin alfa in Canada for cancer patients.

Topics: Anemia; Antineoplastic Agents; Canada; Dose-Response Relationship, Drug; Erythropoietin; Humans; Meta-Analysis as Topic; Multivariate Analysis; Neoplasms; Treatment Outcome

Topics: Disease Progression; Erythropoietin; Gene Expression Profiling; Humans; Immunohistochemistry; Neoplasms; Receptors, Erythropoietin; Treatment Outcome

Jehovah's Witnesses refuse transfusions of the main blood components. This challenges the safety of performing major surgical procedures. At the Norwegian Radium Hospital, we have taken the views of Jehovah's Witnesses regarding blood transfusions into account when planning major surgical procedures and perform these without such transfusions. We present a case and our experiences and routines when performing major cancer surgery on Jehovah's Witness patients.. The medical records of Jehovah's Witnesses, who underwent major surgery at the Norwegian Radium Hospital from April 1992 to February 2006, were surveyed retrospectively. Based on relevant literature, our routines and methods are discussed along with some legal and ethical aspects.. Major transfusion-free surgery can be performed successfully on Jehovah's Witnesses. This requires advanced planning, good routines and close collaborative team efforts. The most relevant techniques to make major surgery feasible are preoperative optimalisation of the haemoglobin levels and acute normovolemic haemodilution and the use of cell saver under surgery.

Topics: Adenocarcinoma; Aged; Blood Transfusion; Erythropoietin; Female; Hemodilution; Humans; Jehovah's Witnesses; Male; Neoplasms; Patient Care Planning; Rectal Neoplasms; Religion and Medicine; Retrospective Studies

Several drug administration regimens of epoetin alfa (EPO) and darbepoetin alfa (DARB) are used for the management of anemia in cancer patients in the clinical practice setting.. The purpose of the present analysis was to assess whether drug administration regimens were associated with differences in the number of provider office visits and hemoglobin assessments during treatment with these agents.. Data from 4 observational studies that examined treatment patterns of EPO and DARE and health care resource utilization were analyzed. These studies, selected based on the availability of office visit and/or hemoglobin determination data during the course of treatment, included a retrospective chart review, 2 retrospective claims analyses, and an ongoing prospective patient registry. The treatment patterns and oncology-related provider visits and/or the frequency of hemoglobin evaluations among the studies were reported.. Data from 15,845 cancer patients were included in the analysis. The patient demographic and baseline characteristics were similar across all 4 studies; patients were predominantly women (62%-71%) with a mean age range of 56 to 63 years. Mean treatment duration ranged from 7.1 to 8.4 weeks without significant differences between EPO and DARE in any study. Weekly and extended (at least every 2 weeks [> or =Q2W]) drug administration frequencies were observed in both treatment groups. The most frequent drug administration schedule for EPO was once weekly (53%-75% of patients), and for DARE Q2W (67%-73%). Despite the difference in erythropoietic agent administration frequency, no significant differences were observed between EPO and DARB for either the number of oncology-related provider visits or the number of hemoglobin assessments.. The frequency of oncology-related provider visits and hemoglobin assessments appears to be independent of the EPO and DARB administration frequency. These findings might provide useful information for health care providers and oncology patients in understanding patterns of care during treatment with erythropoietic agents.

Topics: Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Office Visits; Recombinant Proteins

This study set out to identify the resource use and time commitment associated with treatment of anaemia with erythropoietic therapy, for both haematology/oncology clinics and patients.. The study was carried out at three haematology/oncology clinics in the US, and included 124 cancer patients with anaemia. Stages in the administration of epoetin alfa were identified (preparation, injection and documentation). At each site a trained researcher observed medical staff and recorded the time taken for each stage, in minutes, using a stopwatch. The supplies used for each stage were also recorded. Travel times, waiting times and demographics for patients and caregivers attending the clinic were obtained from self-report questionnaires during the clinic visit. In total, 177 injections of epoetin alfa were administered.. Total mean time clinic staff and patients spent on treatment visits.. The total mean time expended by clinic staff for each injection, including preparation, administration, documentation and phlebotomy, was 25.5 minutes (range 18.6-31.2 at individual centres). The total mean time requirement for patients (time spent travelling to and from the clinic, time spent waiting for the epoetin alfa injection) was 83 minutes.. Treatments that may reduce the time burden of anaemia management should be considered.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Caregivers; Cost-Benefit Analysis; Epoetin Alfa; Erythropoietin; Female; Health Resources; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Recombinant Proteins; Time Factors

Topics: Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Risk

One important feature of human solid tumors is the presence of a hypoxic microenvironment. Under hypoxia, genes that contain a hypoxia-response element (HRE) can be activated by the binding of hypoxia-inducible factor-1. To reach the goal of selectively killing tumor cells in a hypoxic microenvironment using a gene therapy approach, we developed a cytosine deaminase (CD) gene construct (pH9YCD2) that contains an HRE gene enhancer. CD is an enzyme that catalyzes the conversion of noncytotoxic 5-fluorocytosine (5-FC) to the cytotoxic and radiosensitizing drug 5-fluorouracil (5-FU). Yeast CD was cloned into an SV40 promoter-based mammalian expression vector, and an HRE enhancer was inserted in front of the promoter. Human glioblastoma U-87 MG cells were transfected with pH9YCD2. Western blots revealed that CD was strongly expressed under hypoxic conditions (0.3-1% O2), whereas only minor CD expression was seen under normoxic conditions. To confirm that the expressed CD enzyme retains catalytic activity, we performed a 5-FC/5-FU-conversion assay in which 5-FC was incubated with the lysates of pH9YCD2-transfected cells. The percentage of conversion from 5-FC to 5-FU was 63% under hypoxia versus 13% under normoxia. In vitro, cell viability and colony-forming efficiency assays demonstrated that the gene construct was able to significantly kill glioblastoma cells in a hypoxia-dependent manner. In addition, 5-FC treatment of hypoxic pH9YCD2-transfected cells produced a marked bystander effect, which could be a distinct advantage for gene therapy. If this construct exhibits antitumor efficacy in vivo, it may have promise as an antitumor agent in humans.

Topics: Blotting, Western; Cell Hypoxia; Cell Line, Tumor; Cytosine Deaminase; Enhancer Elements, Genetic; Erythropoietin; Flucytosine; Fluorouracil; Genetic Therapy; Genetic Vectors; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Neoplasms; Prodrugs; Simian virus 40; Transcription Factors; Transfection; Tumor Stem Cell Assay; Yeasts

Topics: Anemia; Antineoplastic Agents; Drug Interactions; Erythropoietin; Humans; Infusions, Intravenous; Iron; Neoplasms; Quality of Life; Recombinant Proteins; Reproducibility of Results; Research Design

To review the effects on hemoglobin and quality of life of an every-two-week (Q2W) regimen of the erythropoietic agent darbepoetin alfa for treating patients with chemotherapy-induced anemia.. Published articles and abstracts.. Darbepoetin alfa Q2W increases hemoglobin in patients with chemotherapy-associated anemia and is well tolerated. Increased hemoglobin is associated with improvements in fatigue and energy level. A starting dose of darbepoetin alfa 3.0 mcg/kg (approximately 200 mcg for an average 70 kg patient) Q2W produces a similar level of response to recombinant human erythropoietin.. Darbepoetin alfa effectively treats chemotherapy associated anemia with fewer clinic visits and fewer injections than are required with conventional erythropoietic therapy.. The less-frequent dosing schedule of darbepoetin alfa can simplify anemia management for nurses and other clinic staff, and it offers patients greater freedom in their day-to-day activities, less dependence on caregivers, and less injection-associated discomfort.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Darbepoetin alfa; Drug Administration Schedule; Erythropoietin; Hemoglobins; Humans; Neoplasms; Quality of Life; Treatment Outcome

There are conflicting data about the effects of cisplatin on erythropoietin (EPO) response to anemia. Aim of our study was to investigate whether endogenous EPO response to anemia in cisplatin treated patients was insufficient in comparison to the anemic chemotherapy-naive cancer patients and non cancer patients with iron deficiency anemia. Patients who had hemoglobin (Hb) levels of less than 110 g/l were included in the study. Fifteen chemotherapy- naive cancer patients were enrolled in Group A. Group B consisted of 15 patients who had been treated with three cycles of cisplatin chemotherapy and then became anemic and in Group C were included 15 patients who had iron deficiency anemia, without any malignancy. The mean Hb values were not different between all groups (102.8+/-39.8 g/l, 103.1+/-2.5 g/l and 99.3+/-3.6 g/l in Group A, Group B and Group C, respectively). However, EPO levels were found to be significantly lower in Group A and Group B than Group C (29.63+/-9.09 mU/ml, 20.87+/-2.43 mU/ml and 85.38+/-25.72 mU/ml, respectively; p=0.017 Group A vs. Group C, p=0.005 Group B vs. Group C). No significant difference was found between Group A and B (p=0.917). Opposite the iron deficiency anemia, cancer anemia is associated with an inadequate EPO response to anemia and administration of cisplatin does not lead to it further deterioration.

Topics: Anemia; Anemia, Iron-Deficiency; Antineoplastic Agents; Cisplatin; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms

Anaemia is a common haematological complication of cancer and cytotoxic treatment. The incremental economic burden associated with medical care and short-term disability of anaemia in patients with malignancy and receiving chemotherapy has not been well documented. This study evaluates the effect of anaemia on the costs associated with cancer treated with chemotherapy.. Patients receiving chemotherapy within 6 months of their initial cancer diagnosis were identified in a commercial claims database for 1999-2000. Data for these individuals were linked to their employers' short-term disability records via unique encrypted personal identification numbers provided by employers. Patients with anaemia were identified by a diagnosis of anaemia or treatment with transfusion or erythropoietin alfa (EPO). Healthcare expenditure and short-term disability leave were observed for up to 6 months following initial cancer diagnosis and were summarised into monthly averages. Exponential conditional mean models and zero-inflated negative binomial models were used to analyse mean monthly healthcare expenditures and short-term disability days.. Twenty-five percent of the 619 newly diagnosed cancer patients treated with chemotherapy had anaemia. The presence of anaemia and longer length of transfusion therapy were associated with increased expenditures, while longer length of EPO treatment was associated with lower expenditures. The incremental costs due to anaemia among patients receiving chemotherapy were US$5,538 (year 2001 values) per month in the first 6 months following cancer diagnosis, 10.8% of which were costs related to short-term disability leave.. Anaemia in patients undergoing chemotherapy presents a substantial burden to employers and payers. The findings also suggest that patients with anaemia treated with erythropoietin alfa can achieve expenditure levels similar to those patients without anaemia.

Topics: Adult; Aged; Anemia; Cost of Illness; Erythropoietin; Female; Health Care Costs; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins

We previously showed that nutritional protein concentrations were predictive of outcome, whereas variables reflecting body composition and dialysis dose were not, in a 30-month prospective follow-up of 1,610 hemodialysis patients. Information on dialysis membrane and erythropoietin use had to be evaluated in an additional follow-up.. A subset of 650 patients from the initial cohort of 1,610 was analyzed for survival in a 2-year extension of follow-up. Detailed data were collected: demographics; cause of renal failure; time on dialysis therapy; type of membrane; erythropoietin treatment; body mass index (BMI); predialysis albumin, prealbumin, and bicarbonate levels; and outcome. Normalized protein catabolic rate (nPCR), dialysis adequacy, and lean body mass were computed from predialysis and postdialysis urea and creatinine values.. Patient characteristics were age of 61 +/- 16 years, 58% men, BMI of 22.7 +/- 4.4 kg/m2 , time on dialysis therapy of 102 +/- 73 months, and 8.8% had diabetes. Dialysis parameters were duration of 247 +/- 31 minutes, Kt/V of 1.4 +/- 0.3, and nPCR of 1.2 +/- 0.3 g/kg/d. Albumin level was 3.73 +/- 0.53 g/dL (37.3 +/- 5.3 g/L), and prealbumin level was 31 +/- 8 mg/dL. The survival rate was 78.7% after 2 years. Survival was influenced by age, presence of diabetes, use of high-flux membrane, and serum albumin level, but not other variables, including Kt/V and prealbumin level. Two-year variations in values for urea, creatinine, and weight were predictive of survival in univariate, but not multivariate, analyses.. In patients on dialysis therapy for a long period, better survival was observed when high-flux dialysis membranes were used.

Topics: Aged; Bicarbonates; Body Composition; Body Mass Index; Cardiovascular Diseases; Cause of Death; Cholesterol; Comorbidity; Creatinine; Diabetic Nephropathies; Erythropoietin; Female; Follow-Up Studies; Humans; Infections; Kidney Failure, Chronic; Life Tables; Male; Membranes, Artificial; Middle Aged; Neoplasms; Permeability; Prealbumin; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Protein-Energy Malnutrition; Renal Dialysis; Serum Albumin; Survival Analysis; Time Factors; Urea

Controversy continues to persist about the role of histopathology regarding diagnosis of polycythemia vera (PV). For this reason, a clinicopathological study was performed on 334 patients presenting with a sustained borderline to marked erythrocytosis (hemoglobin >17 g/dl in men and >15 g/dl in women). The aim was to elucidate the discriminating impact of bone marrow biopsy examinations in an independent fashion from laboratory parameters. According to morphological findings based on a semiquantitative evaluation of standardized features, cellularity, megakaryocytes (quantity, size, pleomorphous aspect, clustering, nuclear lobulation), eosinophils, cellular debris, perivascular plasmacytosis and iron-laden macrophages exerted a distinctive value. Comparison with clinical data and follow-up revealed that in only 13 patients (4%), histopathology failed to differentiate clearly between PV (208 patients) and secondary polycythemias (113 patients). In conclusion, certain sets of morphological parameters allow a distinction between autonomous and reactive polycythemias and therefore enhance significantly diagnostic validity.

Topics: Adult; Aged; Bone Marrow; Bone Marrow Cells; Bone Marrow Examination; Cell Count; Cell Size; Eosinophils; Erythropoietin; Female; Hematocrit; Humans; Iron; Macrophages; Male; Megakaryocytes; Middle Aged; Neoplasms; Organelles; Plasma Cells; Pneumonia; Polycythemia; Polycythemia Vera; Primary Myelofibrosis; Reticulin; Retrospective Studies; Sensitivity and Specificity; Smoking

Topics: Anemia; Erythropoietin; Humans; Neoplasms; Recombinant Proteins; Risk

It is well recognized that anemia-induced tumor hypoxia is associated with a reduced sensitivity of tumors to radiation and some forms of chemotherapy. Thus, the correction of lower hemoglobin (Hb) concentrations with recombinant human erythropoietin (rHuEPO) can play an essential role by improving tumor oxygenation. Based on evidence from a number of trials, treatment with rHuEPO will effectively ameliorate anemia and improve quality of life. However, one of the most essential prerequisites for achieving this benefit is the use of rHuEPO in agreement with the evidence-based ASCO/ASH-guidelines recommending a target Hb concentration of 12 g/dl (7.44 mmol/l).

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Comorbidity; Erythropoietin; Health Care Costs; Hemoglobins; Humans; Neoplasms; Practice Guidelines as Topic; Practice Patterns, Physicians'; Recombinant Proteins

The aim of this study was to evaluate the effectiveness and the impact of once-weekly administration of epoetin alfa (Ea) on the management of anaemia and on the quality of life (QOL) of cancer patients receiving chemotherapy. Eighty cancer patients with life expectancy > or = 24 weeks and haemoglobin (Hb) levels < 10.5 g/dL were studied. After an initial screening of patients' demographic and clinical characteristics, Ea 40000 U once a week was administered over a period of 4 months. In case of patients with Hb level exceeding > 14 g/dL or in case of non-response, the dosage was reconsidered. Every month, data regarding Hb levels, clinical variations, changes in the chemotherapy regimen and transfusion use since the last study visit, were evaluated. The Linear Analogue Scale Assessment scale was used for the evaluation of the QOL. The readmissions to hospital rates (P < 0.002) and the transfusion use rates (P < 0.003) were significantly decreased comparatively with baseline. A mean increase from baseline to the final Hb level (P < 0.001) was established, as well as a significant improvement in the functional ability, energy and in the overall QOL (P < 0.001). In conclusion, the treatment of cancer patients with Ea once-weekly is effective and safe, improving their haematological parameters and QOL.

Topics: Adult; Aged; Anemia; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins; Treatment Outcome

Topics: Anemia, Hypochromic; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Topics: Antineoplastic Agents; Clinical Trials as Topic; Erythropoietin; Humans; Neoplasms; Prognosis; Risk Assessment; Risk Factors; Survival Analysis; Treatment Outcome

Topics: Anemia; Clinical Trials as Topic; Disease Progression; Drug Administration Routes; Erythrocyte Count; Erythrocyte Transfusion; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Topics: Anemia; Antineoplastic Agents; Disease-Free Survival; Erythrocyte Count; Erythropoietin; Hemoglobinometry; Humans; Neoplasms; Practice Guidelines as Topic; Recombinant Proteins

Several recently published clinical trials in anaemic patients with cancer provide convincing evidence that the quality of life of such patients is considerably impaired and that a significant improvement in quality of life can be achieved if their anaemia is corrected by treatment with recombinant erythropoietin (epoetin alfa, Eprex). Findings of some of the major studies are summarised in this issue. These summaries have been prepared to make the findings more accessible to busy clinicians who may not have time to read longer reports in specialist journals but who need to understand the important clinical implications of this research.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Quality of Life; Recombinant Proteins; United Kingdom

Topics: Anemia; Clinical Trials as Topic; Erythropoiesis; Erythropoietin; Humans; Neoplasms

Topics: Activities of Daily Living; Adult; Aged; Erythropoietin; Frail Elderly; Geriatric Assessment; Humans; Life Expectancy; Medical Oncology; Neoplasms

Topics: Anemia; Breast Neoplasms; Erythropoietin; Humans; Neoplasms; Prognosis; Recombinant Proteins; Risk Factors; Survival Analysis

The objective of this observational study was the early evaluation of the impact, a week after the first administration of epoetin alfa 40000 U once weekly and i.v. dose of 62.5 mg sodium ferric gluconate for seven days in improving hemoglobin levels in cancer patients affected by mild/moderate or severe anemia during chemotherapy. Twenty patients affected by solid tumors who received epoetin alfa 40000 U once weekly and daily i.v. sodium ferric gluconate for one week were evaluated: 90% of the patients showed hemoglobin increase, with a median level of hemoglobin increase of 0.73 g/L from baseline, and 50% of them showing a hemoglobin increase > 1 gr/L. The treatment was well tolerated and no adverse event was observed. The early increase of hemoglobin level from baseline is interesting and suggestive for the possibility of achieving an adequate hemoglobin level with a short-term treatment. It is still necessary to further explore the real need of iron supplementation to maintain adequate erythropoiesis prior and during epoetin therapy.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Dietary Supplements; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Infusions, Intravenous; Iron; Male; Middle Aged; Neoplasms; Recombinant Proteins; Treatment Outcome

This retrospective observational survey assessed, in a routine clinical practice setting, the modalities of treatment with recombinant erythropoietic agents: alpha erythropoietic agents [epoetin alpha (Eprex) and darbepoetin alpha (Aranesp)] and epoetin beta (NeoRecormon). Evolution of haematological response parameters such as haemoglobin (Hb) during treatment of anaemic patients with cancer were contrasted for the different agents. Records of 125 consecutive adult cancer patients (42 epoetin alpha, 40 epoetin beta, 43 darbepoetin alpha) receiving chemotherapy and erythropoietic treatment for anaemia, and treated between September 2003 and February 2004, were analysed. Mean periods of observation of treatment were 103 days (epoetin alpha), 114 days (epoetin beta) and 95 days (darbepoetin alpha). The mean changes in maximum Hb level during treatment were 2.8 g/dl (epoetin alpha), 3.3 g/dl (epoetin beta) and 2.1 g/dl (darbepoetin alpha) (P=0.02, epoetin beta versus darbepoetin alpha). The proportions of patients achieving > or =1 g/ dl Hb increases were 85.7% (epoetin alpha), 87.5% (epoetin beta) and 79.1% (darbepoetin alpha). The mean cumulative doses administered to achieve these increases were 284, 722 IU; 201, 428 IU; and 208, 823 IU [dose calculated (based on equivalent peptide mass) using 1 microg darbepoetin alpha is equivalent to 200 IU epoetin], respectively. The proportions of patients achieving > or =2 g/dl Hb increases were 66.7% (epoetin alpha), 77.5% (epoetin beta) and 58.1% (darbepoetin alpha). This survey suggests that in real-life clinical conditions the available erythropoietic agents increase Hb effectively in anaemic patients with cancer, and that epoetin beta therapy may have therapeutic advantages over the other agents assessed.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Blood Transfusion; Darbepoetin alfa; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Retrospective Studies; Time Factors; Treatment Outcome

Earlier studies showing a negative impact of anaemia on quality of life (QOL) lack adequate adjustment for confounding factors such as disease stage and tumour response. We examined the impact of haemoglobin concentration on QOL scores of 745 multiple myeloma patients followed from diagnosis, adjusting for objective disease parameters. Data from two Nordic studies with the EORTC QLQ-C30 questionnaire were analysed using linear regression analysis. Haemoglobin was independently related only to fatigue at baseline (P = 0.001) and at 12 months (P = 0.010). In multivariate analysis, extent of skeletal disease was at least as strong a predictor for fatigue at diagnosis as haemoglobin and was also related to other important QOL scores such as physical functioning, role functioning, global QOL and pain (P < 0.001). At 12 months' follow-up, response to therapy was related to physical functioning (P < 0.001) and pain (P = 0.001). In conclusion, haemoglobin and extent of skeletal disease were both predictors for fatigue in patients with newly diagnosed multiple myeloma, but extent of skeletal disease was also associated with other important QOL scores. During follow-up, response to therapy emerged as an important predictor variable. When examining the effect of haemoglobin on QOL, it is essential to adjust for disease parameters and response to therapy in order not to overestimate the impact of haemoglobin on QOL. Our findings imply that uncontrolled studies on the effect of erythropoietin (EPO) in cancer patients may be making exaggerated claims for the effect of EPO on QOL.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Bone Diseases; Erythropoietin; Fatigue; Female; Hemoglobins; Humans; Male; Middle Aged; Multiple Myeloma; Neoplasms; Norway; Physical Endurance; Quality of Life; Regression Analysis; Surveys and Questionnaires; Treatment Outcome

To compare the cost-effectiveness of epoetin alfa (EPO) and darbepoetin alfa (DARB) for the treatment of chemotherapy-induced anemia (CIA), using dosing regimens approved by the FDA (EPO 40,000 U once weekly and DARB 2.25 U once weekly and DARB 2.25 mcg/kg once weekly).. The study compared published results of two double-blind, randomized, phase III trials one utilizing EPO (N = 166) and the other, DARB (N = 367). Patients in both trials similar baseline characteristics. Effectiveness was measured as the proportion of EPO or DARB patients who were successfully treated (i.e., did not require blood transfusion) during weeks 0-16 and 5-16, respectively. Estimated drug costs were presented in 2005 USD based on wholesale acquisition cost (WAC) and average drug utilization over 16 weeks. Cost-effectiveness was calculated as the estimated drug costs divided by transfusion effectiveness. Threshold analysis was used to determine the break-even point at which EPO and DARB had the same drug costs.. Estimated drug costs over 16 weeks were $9,039 for EPO and $13,555 for DARB. During weeks 5-16, 85% of EPO patients and 73% of DARB patients were successfully treated, resulting in average cost-effectiveness ratios of $106 for EPO and $186 for DARB per one per cent of successfully treated patients. A 33% reduction in DARB WAC was required to achieve the same drug costs as for EPO.. Utilizing FDA-approved doses, EPO was found to result in lower drug costs and better treatment success when compared to DARB. Hence, EPO is a dominant alternative compared to DARB for the treatment of CIA. The analyses presented here are not without limitations. Specifically, although the studies were comparable, patients were ultimately drawn from different populations.

Topics: Anemia; Antineoplastic Agents; Clinical Trials, Phase III as Topic; Darbepoetin alfa; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins

Topics: Anemia; Clinical Trials as Topic; Darbepoetin alfa; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Patient Selection; Recombinant Proteins

Anemia of patients with malignancy might have various reasons. No matter if its background is the underlying tumorous disease or chemo- and/or radiotherapy, it can cause fatigue, malaise, it certainly decreases the patients' quality of life and, furthermore, shortens their survival. Chronic hypoxia caused by anemia promotes tumor progression by several mechanisms e.g. by enhancing angioneogenesis by the production of VEGF. At the same time it decreases the efficacy of chemo- and radiotherapy. Therefore, prevention and/or correction of chemo/radiotherapy-induced anemia is a major goal of modern oncotherapy.

Topics: Anemia; Antineoplastic Agents; Chemotherapy, Adjuvant; Erythropoietin; Hematinics; Humans; Hypoxia; Neoplasms; Radiotherapy, Adjuvant; Survival Rate

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Drug Interactions; Erythropoietin; Humans; Neoplasms; Predictive Value of Tests; Recombinant Proteins

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Fatigue; Hemoglobins; Humans; Neoplasms; Quality of Life; Survival Analysis

Topics: Anemia; Blood Transfusion; Clinical Trials as Topic; Erythropoietin; Forecasting; Guidelines as Topic; Hematinics; Hemoglobins; Humans; Incidence; Neoplasms; Quality of Life; Treatment Outcome

Although previous studies have recognized that timely correction of anemia is desirable, no published research quantifies the association between the timeliness of the hemoglobin rise and patients' outcomes. This study evaluates whether anemic patients with cancer who are receiving chemotherapy and who experienced an early response to epoetin alfa (> or = 1 g/dL hemoglobin increase at the end of 4 weeks of treatment) experienced better clinical and drug utilization outcomes compared with patients who did not experience an early response. Three large, open-label, community studies of epoetin alfa for the treatment of chemotherapy-related anemia were retrospectively analyzed to assess the association of early hemoglobin response to subsequent transfusion requirements, subsequent hemoglobin response, quality of life, and epoetin alfa dosage administered over the study. Two epoetin alfa dosing regimens were evaluated: 10,000 units 3 times weekly with potential escalation to 20,000 units, and 40,000 units once weekly with potential escalation to 60,000 units. In all studies, patients who experienced an early hemoglobin response had statistically lower subsequent transfusion requirements, higher rates of subsequent hemoglobin response, shorter time to hemoglobin response, better improvements in quality of life scores, and lower average weekly epoetin alfa dose than patients who did not experience an early hemoglobin response. Similar proportions of patients experienced early response in the 3-times weekly and once-weekly epoetin alfa regimens. This ad hoc analysis found that early hemoglobin response to epoetin alfa therapy was associated with improved clinical benefits and drug utilization. Early hemoglobin response may therefore be considered as a desired goal of epoetin alfa therapies.

Topics: Aged; Anemia; Antineoplastic Agents; Blood Transfusion; Cohort Studies; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Multivariate Analysis; Neoplasms; Quality of Life; Recombinant Proteins; Retrospective Studies; Time Factors; Treatment Outcome

The cost of darbepoetin alfa versus that of epoetin alfa in a hospital setting was studied.. The study was an observational, retrospective review of the hospitalwide use of darbepoetin and epoetin during hospital admissions beginning in the period from January 2003 through April 2003. After the identification from daily charge reports of patients who used at least one of the study drugs during an admission, charts were requested for review. Drug product costs were determined from hospital purchasing information. Material and labor costs were combined to estimate drug administration costs. Total costs were calculated as the sum of drug product costs and administration costs.. A total of 429 epoetin records and 80 darbepoetin records were included. The two cohorts were similar with respect to demographic characteristics. With respect to costs, the only significant difference between cohorts was in daily administration costs, which were lower for patients receiving darbepoetin. Sensitivity analysis found lower costs for darbepoetin only after the dose-conversion ratio (DCR) was increased to above 256.74 units:1 microg. The overall DCR based on the median daily dose of each drug was 244.90 units:1 microg.. A cost-minimization study in a hospital showed no cost difference between treatment with epoetin and darbepoetin.

Topics: Anemia; Darbepoetin alfa; Drug Costs; Epoetin Alfa; Erythropoietin; Hemoglobins; Hospital Costs; Hospitals; Humans; Kidney Diseases; Length of Stay; Neoplasms; Recombinant Proteins

Topics: Anemia; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

To assess physician use of erythropoietin in cancer patients before publication of the American Society of Clinical Oncology/American Society of Hematology guidelines.. Questionnaires about erythropoietin use in practice and 12 hypothetical clinical scenarios involving patients with cancer were mailed to 2000 oncologists/hematologists in the United States and 19 other countries. Response rates were 30% in the United States and 25% internationally. Data on erythropoietin use for ovarian cancer were obtained from one clinical trial. Multivariate regression models assessed predictors of erythropoietin prescription.. Most physicians selected a hemoglobin level < or =10 g/dL as an upper threshold for erythropoietin use (36% to 51% of U.S. physicians and 21% to 32% of foreign physicians). Frequent erythropoietin use (defined as use in at least 10% of cancer patients) was higher in the United States than elsewhere (adjusted odds ratio [OR] = 5.8; 95% confidence interval [CI]: 2.5 to 13.4). Among U.S. physicians, those who said they used erythropoietin frequently were more likely to be in fee-for-service than managed care settings (OR = 2.2; 95% CI: 1.3 to 3.7). Those who reported never using erythropoietin practiced in countries that had lower annual per capita health care expenditures, lower proportions of privately funded health care, and a national health service (P <0.05 for all comparisons). Of 235 ovarian cancer patients who received topotecan, 38% (45/118) of U.S. patients and 2% (2/117) of European patients who developed grade 1 anemia (hemoglobin level between 10 and 12 g/dL) were treated with erythropoietin (P <0.01).. Financial considerations and a hemoglobin level <10 g/dL appear to influence erythropoietin use in the United States, whereas financial considerations alone determine erythropoietin use abroad.

Topics: Anemia; Antineoplastic Agents; Confidence Intervals; Cost Savings; Cross-Cultural Comparison; Drug Utilization; Erythropoietin; Fee-for-Service Plans; Female; Health Expenditures; Hemoglobinometry; Humans; Male; Managed Care Programs; Medical Oncology; Neoplasms; Odds Ratio; Ovarian Neoplasms; Practice Guidelines as Topic; Practice Patterns, Physicians'; Regression Analysis; Topotecan; United States

Epoetin alfa administered s.c. three times weekly or once weekly increases hemoglobin (Hb) levels, decreases transfusion requirements, and improves quality of life in anemic cancer patients receiving chemotherapy. This study assessed the feasibility of using higher initial doses of once-weekly epoetin alfa followed by less frequent maintenance doses to increase and then maintain adequate Hb levels in this population.. In this open-label, nonrandomized, pilot study, anemic (baseline Hb < or = 11 g/dl) cancer patients undergoing chemotherapy received initial doses of epoetin alfa of 60,000 U s.c. once weekly to increase Hb levels by at least 2 g/dl, followed by 120,000 U s.c. every 3 weeks to maintain Hb levels. The maximum treatment duration was 24 weeks.. The mean baseline Hb level was 10.1 +/- 0.8 g/dl (n = 20). Once-weekly dosing resulted in mean Hb level increases of 1.0 +/- 1.1 g/dl by week 4 and 2.9 +/- 1.9 g/dl by week 8; 86% and 79% of patients evaluable at week 8 and week 12, respectively, demonstrated increases of at least 2 g/dl (target Hb level of > or = 12 g/dl). Thirteen patients (65%) received at least one maintenance dose; the mean Hb level increased from 12.8 +/- 1.1 g/dl before starting maintenance therapy to 13.3 +/- 1.4 g/dl at the last maintenance week. Both dosage regimens were well tolerated.. Once-weekly epoetin alfa at a dose of 60,000 U effectively increased Hb levels by week 8; 86% of patients achieved rises of at least 2 g/dl or Hb levels > or = 12 g/dl. Moreover, epoetin alfa at doses of 120,000 U every 3 weeks maintained or increased Hb levels. Results from this pilot study suggest that higher initial once-weekly dosing of epoetin alfa followed by less frequent maintenance dosing appears to be feasible for treating anemia in cancer patients undergoing chemotherapy. Further evaluation of these and other epoetin alfa dosage regimens is warranted.

Topics: Adult; Anemia; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Pilot Projects; Practice Guidelines as Topic; Recombinant Proteins

Topics: Adult; Cardiovascular Diseases; Decision Making; Disease Progression; Epoetin Alfa; Erythropoietin; Female; Glomerulosclerosis, Focal Segmental; Hematinics; Humans; Kidney Failure, Chronic; Kidney Transplantation; Morbidity; Neoplasms; Pregnancy; Pregnancy Complications; Recombinant Proteins; Renal Dialysis; Renal Replacement Therapy; Risk Assessment; Uremia

The hypoxia-inducible factor-1 (HIF-1) transcription factor is an important regulator of tumor response to hypoxia that include increased angiogenesis, glycolytic metabolism, and resistance to apoptosis. HIF-1 activity is regulated by the availability of the HIF-1alpha subunit, the levels of which increase under hypoxic conditions. PX-478 (S-2-amino-3-[4'-N,N,-bis(2-chloroethyl)amino]phenyl propionic acid N-oxide dihydrochloride) is an inhibitor of constitutive and hypoxia-induced HIF-1alpha levels and thus HIF-1 activity. We report that PX-478 given to mice suppresses HIF-1alpha levels in HT-29 human colon cancer xenografts and inhibits the expression of HIF-1 target genes including vascular endothelial growth factor and the glucose transporter-1. PX-478 shows antitumor activity against established (0.15-0.40 cm(3)) human tumor xenografts with cures of SHP-77 small cell lung cancer and log cell kills up to 3.0 for other tumors including HT-29 colon, PC-3 prostate, DU-145 prostate, MCF-7 breast, Caki-1 renal, and Panc-1 pancreatic cancers. Large (0.83 cm(3)) PC-3 prostate tumors showed 64% regression, which was greater than for smaller tumors. The antitumor response to PX-478 was positively correlated with tumor HIF-1alpha levels (P < 0.02) and was accompanied by massive apoptosis. The results show that PX-478 is an inhibitor of HIF-1alpha and HIF-1 transcription factor activity in human tumor xenografts and has marked antitumor activity against even large tumor xenografts, which correlates positively with HIF-1alpha levels.

Topics: Animals; Antineoplastic Agents; Apoptosis; Area Under Curve; Blotting, Western; Cell Line, Tumor; Erythropoietin; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Mice, SCID; Monosaccharide Transport Proteins; Mustard Compounds; Neoplasm Transplantation; Neoplasms; Phenylpropionates; Time Factors; Transcription Factors; Vascular Endothelial Growth Factor A

Topics: Anemia; Cell Hypoxia; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Disease Models, Animal; Dose Fractionation, Radiation; Epoetin Alfa; Erythropoietin; Female; Head and Neck Neoplasms; Hematinics; Hemoglobins; Humans; Male; Meta-Analysis as Topic; Neoplasm Recurrence, Local; Neoplasms; Pelvic Neoplasms; Placebos; Prognosis; Radiotherapy Dosage; Recombinant Proteins; Retrospective Studies; Risk; Risk Factors; Time Factors; Treatment Outcome; Uterine Cervical Neoplasms

To evaluate the efficacy of darbepoetin alfa 200 microg subcutaneously every 2 weeks after therapeutic substitution for epoetin alfa.. Retrospective multicenter chart review.. Three US Oncology-affiliated outpatient sites.. Three hundred thirty anemic patients with nonmyeloid malignancies, of whom 174 had been treated previously with epoetin alfa (switched group) and 156 had not been treated recently with epoetin alfa (naive group).. Therapeutic substitution with darbepoetin alfa was started according to the US Oncology Pharmacy and Therapeutics Committee's recommended dosing guidelines: anemic patients with cancer received a starting dosage of darbepoetin alfa 200 microg every 2 weeks regardless of whether or not they had previously received epoetin alfa. Hematologic and darbepoetin alfa usage data were abstracted from consecutive medical records dated from May 2002-March 2003.. Median exposure to darbepoetin alfa was 10 weeks (25th quartile 6 wks, 75th quartile 17 wks) and 10 weeks (25th quartile 5 wks, 75th quartile 18 wks) for the naive and switched groups, respectively. The week before the switch to darbepoetin alfa, the 174 patients receiving epoetin alfa were administered the following weekly doses: less than 40,000 U (9%), 40,000 U (50%), or 45,000-90,000 U (41%). Mean hemoglobin level increased from baseline (wk 0) in both the naive and switched groups. The proportion of patients receiving a red blood cell transfusion in the darbepoetin alfa treatment phase was low (15% in each group). No variation in transfusion rates was observed across weight categories in patients who received a fixed dosage of darbepoetin alfa. Darbepoetin alfa was well tolerated. A detailed usage algorithm was validated by these results and is being used in these three US Oncology-affiliated practices.. A darbepoetin alfa starting dosage of 200 microg subcutaneously every 2 weeks administered according to US Oncology-recommended dosing guidelines is effective in treating chemotherapy-induced anemia in both epoetin alfa-naive patients and those switched from epoetin alfa.

Topics: Aged; Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hemoglobins; Humans; Injections, Subcutaneous; Male; Neoplasms; Practice Guidelines as Topic; Recombinant Proteins; Retrospective Studies; Therapeutic Equivalency; Time Factors; Weight Gain

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Darbepoetin alfa; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centres (FNCLCC), the 20 French cancer centres, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery.. To update the Standards, Options and Recommendations clinical practice guidelines for the use of recombinant erythropoietin (epoietin alpha and beta darbepoietin-alpha, EPO) in the management of anaemia in oncology. To define, on the basis of the critical appraisal of the best available evidence and expert agreement, the clinical situations in which the administration of rHuEPO is indicated, and those in which it is not indicated, except in the setting of randomised controlled trial.. The working group identified the questions requiring up-dating from the previous guideline. Medline and Embase were searched using specific search strategies from January 1999 to October 2002. Literature monitoring was performed to identify randomised clinical trials published between October 2002 to November 2003. In addition several Internet sites were searched in October 2002.. A total of 36 new references, corresponding to 30 randomised clinical trials, were identified. The role of rHuEPO is certain when the haemoglobin concentration is below 10 g/dL, but remains uncertain when the concentration is between 10 g/dL and 12 g/dL. When the haemoglobin concentration is between 12 g/dL and 14 g/dL there is no justification to use rHuEPO to prevent anaemia, except in the setting of autologous blood transfusion programmes before major surgery. No anti-anaemic treatment is justified if the haemoglobin concentration is higher than 14 g/dL, except in the setting of a randomised clinical trial.

Topics: Anemia; Erythropoietin; France; Hemoglobin A; Humans; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins

Clinical uses for recombinant human erythropoietin (rHuEPO) therapy continue to expand. Initial use was in anaemia associated with end-stage renal disease, but more recently there have been many reports of the benefits of erythropoietin in other clinical situations such as cancer-related anaemia. Recombinant erythropoietin reduces the need for blood transfusion and hence exposure to donor blood products as well as improving quality of life. We report four patients who were transfusion dependent, none of whom had licensed indications for the use of recombinant erythropoietin. Two patients had microangiopathic haemolytic anaemia secondary to mechanical valve haemolysis and were unsuitable for any further cardiac intervention. One patient had anaemia of chronic disease and anti-Vel red cell antibodies, making compatible blood transfusions difficult to obtain. The fourth patient had primary thrombocythaemia and developed transfusion-dependent anaemia secondary to myelosuppressive agents. All four patients had a relative deficiency in endogenous erythropoietin levels ranging between 7 and 41 IU/l. After commencing recombinant erythropoietin therapy, all had a response in haemoglobin of at least 1 g/dl with an overall improvement in their quality of life. We conclude that rHuEPO is a very convenient and useful form of treatment in transfusion-dependent anaemia and in some cases beyond the licensed indications.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Blood Group Antigens; Drug Approval; Erythropoietin; Female; Hemolysis; Humans; Kidney Failure, Chronic; Middle Aged; Neoplasms; Recombinant Proteins; Transfusion Reaction

Topics: Anemia; Erythrocyte Transfusion; Erythropoietin; Hematocrit; Humans; Neoplasms; Palliative Care; Prognosis; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Retrospective Studies; Survival Analysis

Topics: Anemia; Antineoplastic Agents; Depression; Erythropoietin; Fatigue; Humans; Neoplasms; Radiotherapy

Topics: Anemia; Breast Neoplasms; Erythropoietin; Female; Head and Neck Neoplasms; Humans; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins

Anemia is a common complication associated with cancer and cancer treatment. As many as 50% to 60% of cancer patients will develop this condition. Fatigue is a major symptom of anemia and is a primary complaint in patients with cancer. Fatigue can be debilitating for patients, reducing their ability to work, decreasing physical and emotional well-being, and interfering with cognitive ability, all of which can lead to anxiety and depression. Despite the high incidence of the disease and the extent of its impact on the cancer patient, anemia remains underdiagnosed and undertreated. Erythropoietic proteins offer a valuable alternative to standard transfusion therapy, and there is increasing evidence that, in addition to raising hemoglobin levels, these therapeutic agents can lead to improvements in quality of life and patient-reported outcomes. The impact of anemia correction on survival is under investigation; a body of evidence suggests a possible benefit, although this has recently been challenged. There is a strong need for increased awareness of cancer-related anemia and the consequences of its lack of treatment.

Topics: Anemia; Erythropoietin; Fatigue; Humans; Neoplasms; Quality of Life

Aranesp (darbepoietin alfa) is a biologically modified form of recombinant human erythropoietin (rHuEpo). Two additional carbohydrate-binding sites give Aranesp a half-life about three times that of rHuEpo. Extensive studies in adults and early studies in children indicate that Aranesp can be administered far less frequently than rHuEpo with an equivalent erythropoietic effect. This article reviews these studies and reports on the in vitro effects of Aranesp on human fetal and neonatal erythroid progenitors.

Topics: Adult; Anemia; Darbepoetin alfa; Erythropoietin; Humans; Infant, Newborn; Kidney Failure, Chronic; Neoplasms; Pediatrics; Randomized Controlled Trials as Topic; Technology, Pharmaceutical

Anemia in cancer patients is frequent but often underestimated. Anemia affects the health-related quality of life and impacts prognosis and outcome of therapy. Treatment options include the administration of hematopoietic growth factors and red blood cell transfusions. Blood transfusions result in rapid but often transient improvement of anemia. Administration of epoetin or darbepoetin alfa increases hemoglobin levels, decreases blood transfusions, and improves quality of life in patients with cancer. Presently, trials investigate whether treatment of anemic cancer patients with erythropoietin impacts on outcome of chemo- and/or radiotherapy and on overall survival. Oncologists must be aware of the clinical relevance of anemia and offer adequate treatment options to their patients. Supportive treatment of anemic cancer patients presenting anemia-related symptoms should be performed to reduce symptoms in cancer patients and optimize outcome to anticancer therapy.

Topics: Anemia; Blood Transfusion; Darbepoetin alfa; Erythrocyte Transfusion; Erythropoietin; Hematopoietic Cell Growth Factors; Hemoglobinometry; Humans; Neoplasms; Palliative Care; Prognosis; Recombinant Proteins

"The Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centres (FNCLCC), the twenty French cancer centres, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery.. To update the Standards, Options and Recommendations clinical practice guidelines for the use of recombinant erythropoietin (epoietin alpha and beta darbepoietin-alpha, EPO) in the management of anaemia in oncology for patient undergoing radiotherapy.. The working group identified the questions requiring up-dating from the previous guideline. Medline and Embase were searched using specific search strategies from January 1999 to October 2002. Literature monitoring was performed to identify randomised clinical trials published between October 2002 to November 2003. In addition several Internet sites were searched in October 2002.. There is no standard attitude for use of rHuEPO in patients undergoing radiotherapy. There is no evidence to support use of rHuEPO in patients with ENT cancer receiving radiotherapy alone. In patients undergoing curative radiotherapy, it is recommended to correct anaemia under I Og/dL using transfusion rather than rHuEPO. When the haemoglobin concentration is between 12g/dL and 14g/dL initial use of rHuEPO can be an option under certain conditions for radiochemotherapy if the risk of anaemia is high with the chemotherapy regimen used. Anaemic patients should be included in clinical trials to clarify the impact of rHuEPO in terms of local control of the tumour and survival.

Topics: Anemia; Erythropoietin; France; Hemoglobins; Humans; Interinstitutional Relations; Neoplasms; Practice Guidelines as Topic; Quality of Health Care; Radiotherapy; Recombinant Proteins

Topics: Advertising; Anemia; Darbepoetin alfa; Erythropoietin; Hematinics; Humans; Multicenter Studies as Topic; Neoplasms; Prognosis; Randomized Controlled Trials as Topic; Recombinant Proteins; United States; United States Food and Drug Administration

The objective of this retrospective observational cohort study was to compare the effectiveness of darbepoetin alfa with that of epoetin alfa in patients with chemotherapy-induced anemia using data from noncontemporaneous chart audits conducted at a community-based oncology practice.. For the first chart audit, data were collected from consecutive patients with nonmyeloid malignancies with diagnoses of chemotherapy-induced anemia and hemoglobin levels < or = 10.5 g/dl who were receiving concurrent chemotherapy and had at least 5 weeks of visits from July-September 2000. After therapeutic substitution of darbepoetin alfa for epoetin alfa for all patients with chemotherapy-induced anemia, data were collected from consecutive darbepoetin alfa-treated patients with diagnoses of chemotherapy-induced anemia and at least 8 weeks of visits from June-October 2002 (darbepoetin alfa was approved in July 2002).. Most (86%) of the 212 epoetin alfa-treated patients had received an initial dose of 40,000 U once weekly, and most (85%) of the 196 darbepoetin alfa-treated patients had received a fixed dose of either 100 microg once weekly (49%) or 200 microg every 2 weeks (36%). At 8 weeks, the mean change in hemoglobin level was 1.1 g/dl for the darbepoetin alfa patient group and 1.0 g/dl for the epoetin alfa patient group.. Utilization, dose escalation rates, and clinical outcomes were considered comparable for the darbepoetin alfa and epoetin alfa patient groups.. Darbepoetin alfa, 100 microg once weekly or 200 microg every 2 weeks, appears to be as effective as epoetin alfa, 40,000 U once weekly, for the treatment of chemotherapy-induced anemia in the clinical practice setting.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Retrospective Studies; Treatment Outcome

Topics: Anemia; Erythropoietin; Fatigue; Humans; Neoplasms; Nursing Assessment; Nursing Diagnosis; Recombinant Proteins; Syndrome

Research into reducing the side effects of anthracyclines and optimizing patient care and quality of life is constantly evolving. This program took a look at ways that oncology nurses can reduce the toxicities of conventional and novel chemotherapy regimens as well as addressing the erythropoietic agents used to treat patients with anemia.

Topics: Anemia; Anthracyclines; Antineoplastic Agents; Erythropoietin; Hematinics; Humans; Neoplasms; Nurse's Role; Oncology Nursing; Patient Care; Quality of Life; Total Quality Management

Anemia in cancer patients is associated with reduced quality of life and local failure after radiation treatment. However, the use of erythropoietin to correct cancer anemia and to improve radiation efficacy was disappointing. Erythropoietin-receptor signaling mainly acts via activation of STAT 5, but also crossactivates the antiapoptotic transcription factor NF-kappaB. This causes neuroprotection against oxidative stress and implies radioprotection. In order to investigate possible radioprotective effects of erythropoietin-receptor signaling, we used an in vitro model system employing HeLa TetOff cells, stably transfected with an expression vector for the erythropoietin-receptor gene. Using electrophoretic mobility shift assays, we could demonstrate strong activation of NF-kappaB by erythropoietin-receptor signaling in HeLa cells. Activation of NF-kappaB did not require degradation of IkappaBalpha and was not prevented by proteasome inhibition. Furthermore, stimulation with erythropoietin resulted in a 50% increased clonogenicity of erythropoietin-receptor-expressing cells but did not alter radiation sensitivity itself. As most human tumors express erythropoietin receptor, we advocate a restricted use erythropoietin to patients suffering from erythropoietin-receptor-expressing cancers.

Topics: Apoptosis; Cell Line, Tumor; Cell Survival; DNA-Binding Proteins; DNA, Complementary; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Erythropoietin; HeLa Cells; Humans; I-kappa B Proteins; Milk Proteins; Neoplasms; NF-kappa B; NF-KappaB Inhibitor alpha; Radiation Tolerance; Receptors, Erythropoietin; Signal Transduction; STAT5 Transcription Factor; Trans-Activators

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Humans; Iron; Iron-Dextran Complex; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins

Topics: Anemia, Iron-Deficiency; Bone Marrow; Chronic Disease; Cytokines; Erythropoiesis; Erythropoietin; Hematologic Tests; Humans; Inflammation; Iron; Neoplasms

Darbepoetin alfa, a novel erythropoiesis-stimulating protein, is a glycosylation analog of recombinant human erythropoietin (rHuEPO) with two additional N-linked carbohydrates. Used to treat anemia of cancer, chemotherapy, and kidney disease, it has a three-fold longer serum half-life and increased in vivo activity, but decreased receptor-binding activity. Glycosylation analogs with altered N-linked carbohydrate content were compared with rHuEPO to elucidate the relationship between carbohydrate content and activity.. EPO glycosylation analogs and rHuEPO were expressed and, in some cases, purified from Chinese hamster ovary cells and carbohydrate characterized by Western blotting. Assays were performed to compare in vitro receptor binding and in vivo activity of rHuEPO, darbepoetin alfa, and analogs.. Reduced receptor binding of darbepoetin alfa could be accounted for entirely by increased sialic acid content and not by carbohydrate-related stearic hindrance or by amino acid differences. Shapes of dose-response curves, maximal responses in proliferation and colony assays, and magnitude and duration of downstream signaling events were comparable in vitro for rHuEPO and darbepoetin alfa. The in vivo response correlated with the number of N-linked carbohydrates. The number of carbohydrates was a more significant determinant for in vivo activity than position. The differences in in vivo erythropoietic activity among glycosylation analogs were more evident with increased time following administration in exhypoxic polycythemic mice.. Carbohydrate increases persistence of EPO, resulting in a prolonged and increased biological response in vivo, and overcoming reduced receptor-binding activity.

Topics: Anemia; Animals; Carbohydrate Metabolism; Carbohydrates; Cell Proliferation; CHO Cells; Colony-Forming Units Assay; Cricetinae; Darbepoetin alfa; Dose-Response Relationship, Drug; Erythropoietin; Female; Gene Expression; Glycosylation; Half-Life; Hematopoietic Stem Cells; Humans; Kidney Diseases; Mice; Neoplasms; Polycythemia; Protein Binding; Protein Processing, Post-Translational; Receptors, Erythropoietin; Recombinant Proteins; Signal Transduction

Topics: Anemia; Animals; Cell Hypoxia; Clinical Trials as Topic; Disease Models, Animal; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Topics: Anemia; Clinical Trials as Topic; Erythropoietin; Humans; Neoplasms; Risk Factors; Thromboembolism; Treatment Outcome

Topics: Anemia; Antineoplastic Agents; Cancer Care Facilities; Erythropoietin; Fatigue; Humans; Neoplasms; Practice Guidelines as Topic

These guidelines propose a treatment algorithm in which patients are evaluated regularly for fatigue using a brief screening instrument, and are treated as indicated by their fatigue level. The algorithm's goal is to identify and treat all patients with fatigue that causes distress or interferes with their daily activities or functioning. Management of fatigue begins with primary oncology team members who perform the initial screening and either provide basic education and counseling or expand the initial screening to a more focused evaluation for moderate or higher levels of fatigue. At this point the patient is assessed for current disease and treatment status, a review of body systems, and an in-depth fatigue evaluation. In addition, the patient is assessed for the presence of seven treatable factors known to contribute to fatigue: pain, emotional distress, sleep disturbance, anemia, alterations in nutrition, deconditioning, and comorbidities. If any of these conditions are present, they should be treated according to practice guidelines, with referral to other care professionals as appropriate, and the patient's fatigue should be reevaluated regularly. If none of the seven factors are present or the fatigue is unresolved, selection of appropriate fatigue management and treatment strategies is considered within the context of the patient's clinical status: receiving active cancer treatment, receiving disease-free long-term follow-up, or receiving care at the end of life. Management of fatigue is cause-specific when conditions known to cause fatigue can be identified and treated. When specific causes, such as infection, fluid and electrolyte imbalances, or cardiac dysfunction, cannot be identified and corrected, nonpharmacologic and pharmacologic treatment of the fatigue should be considered. Nonpharmacologic interventions may include a moderate exercise program to improve functional capacity and activity tolerance, psychosocial programs to manage stress and increase support, restorative therapies to decrease cognitive alterations and improve mood state, and nutritional and sleep interventions for patients with disturbances in eating or sleeping. Pharmacologic therapy may include drugs, such as antidepressants for depression or erythropoietin for anemia. A few clinical reports of the use of psychostimulants suggest the need for further research on these agents as potential treatment modalities in managing fatigue. Effective management of cancer-related

Topics: Antineoplastic Agents; Erythropoietin; Fatigue; Humans; Mass Screening; Neoplasms; Practice Patterns, Physicians'; Quality of Life; United States

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Europe; Humans; Neoplasms; Patient Advocacy; Practice Guidelines as Topic; Recombinant Proteins

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Darbepoetin alfa; Erythropoietin; Humans; Neoplasms

Topics: Anemia; Erythropoietin; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Topics: Anemia; Erythropoietin; Hemoglobins; Humans; Neoplasms; Recombinant Proteins; Survival Rate

Topics: Androgens; Anemia; Drug Therapy, Combination; Erythropoietin; Humans; Hypogonadism; Male; Neoplasms; Recombinant Proteins

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Topics: Anemia; Autoimmune Diseases; Clinical Trials as Topic; Doping in Sports; Erythropoietin; Humans; Kidney Diseases; Myelodysplastic Syndromes; Neoplasms; Recombinant Proteins; Red-Cell Aplasia, Pure; Treatment Outcome; Uremia

In addition to the chief function of erythropoietin (Epo) in promoting erythropoiesis, some other roles have been found in the brain and uterus. We have reported that signalling pathways of Epo and Epo receptor (EpoR) are involved in the tumourigenesis of ovarian and uterine cancers. To determine whether Epo plays a similar role in other malignancies, we studied the expression of Epo in several malignant human cell lines. We found that 24 malignant human cell lines examined express Epo and EpoR regardless of their origins, types, genetic characteristics and biological properties and secrete a very small amount of Epo individually and that most of them respond to hypoxic stimuli by enhanced secretion of Epo. To determine whether the Epo-EpoR pathway operates in tumours of these cell lines, we transplanted several cell lines into nude mice and confirmed the presence of Epo-responsive sites in xenografts in which the phosphorylation of the STAT5 (signal transducer and activator of transcription) is detectable. Furthermore, in nude mice we blocked the Epo signalling in xenografts of two representative cell lines, stomach choriocarcinoma and melanoma, by i.p. injections of EpoR antagonist and found inhibition of angiogenesis and survival of tumour cells leading to destruction of tumour masses and disturbances of phosphorylation of STAT5. In contrast, Epo mimetic peptide promotes angiogenesis and tumour cell survival. These findings suggest that Epo is indispensable for the growth and viability of malignant tumour and also that the deprivation of Epo signalling may be a promising therapy for human malignancy.

Topics: Cell Division; Erythropoietin; Humans; Neoplasms; Neovascularization, Pathologic; Receptors, Erythropoietin; Signal Transduction; Transplantation, Heterologous; Tumor Cells, Cultured

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hemoglobinometry; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Structure-Activity Relationship; Treatment Outcome

This retrospective case-series review studied the effectiveness of epoetin alfa in community oncology practices, which until now has not been well documented.. We reviewed the medical records of 118 cancer patients treated between 1999 and 2001 with cyclic chemotherapy plus epoetin alfa in 27 US community-based oncology practices. Two analysis sets were examined: one including all patients (n=118) and one including only those patients with no concurrent events impacting hemoglobin data interpretation (n=73). Efficacy of epoetin alfa was evaluated by hemoglobin response (aS2 g/dl increase in hemoglobin from baseline) at weeks 12 and 16, the time to hemoglobin response, and change in hemoglobin concentrations from baseline at specific time points.. After 12 weeks of treatment, 43% (95% confidence interval [CI], 33-54%) of patients had a hemoglobin response, and the proportion of responders further rose to 61% (95% CI, 49-72%) after 16 weeks. The median time to response was 92 days (lower 95% confidence limit, 74 days; upper bound not estimable). Hemoglobin increased from baseline at all time points evaluated during epoetin alfa treatment, with a mean increase of 1.1 g/dl (95% CI, 0.77-1.4 g/dl) by the last observation.. These results indicate that epoetin alfa is effective in community practice, but most patients take longer than 3 months to respond. Because slow responses may negatively impact on the quality of life in these patients, alternative treatment approaches providing faster and perhaps better responses may provide greater clinical benefit.

Topics: Aged; Community Health Services; Drug Evaluation; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Medical Oncology; Middle Aged; Neoplasms; Recombinant Proteins; Retrospective Studies; Time Factors

To explore the clinical significance of serum erythropoietin (EPO) detection in patients with cancer-related anemia for improving the life quality of the cancer patients in advanced stage with repeated chemotherapy.. The serum EPO levels were determined in 38 cases of cancer-related anemia with enzyme-linked immunosorbent assay (ELISA).. In 24 patients, the serum EPO level was elevated above the normal range, and lowered EPO level was detected in only 1 cases.. Normal or elevated serum EPO level in patients with cancer-related anemia indicates strong abilities of the patients in self regulation, having important clinical implications for the use of EPO.

Topics: Adolescent; Adult; Aged; Anemia; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Practice Guidelines as Topic; Recombinant Proteins

Topics: Anemia; Drug Administration Schedule; Erythropoietin; Humans; Neoplasms; Time Factors

Topics: Anemia, Aplastic; Erythropoiesis; Erythropoietin; Humans; Neoplasms; Recombinant Proteins; Red-Cell Aplasia, Pure

A line of transgenic mice overexpressing erythropoietin was created. These mice retained their capacity to reduce their gastro-intestinal absorption of iron and to regulate the changes in their iron metabolism and they could serve as a model for the in vivo study of iron homeostasis and erythropoiesis. NEW INDICATIONS FOR RECOMBINANT HUMAN ERYTHROPOIETIN: After chronic terminal kidney failure, the treatment of chronic dialysed kidney failure patients and patients treated with azathioprine or patients having undergone surgery and requiring transfusion, other indications have been proposed. Such as anaemia in children following inadequate production of endogenous erythropoietin and/or direct inhibition of the erythroid cell line in the bone marrow or anaemia during pregnancy and, since the Sixties, anaemia during cancer. TO ASSESS THE PHYSIOPATHOLOGY OF ANEMIA:In anaemic patients suffering from a malignant blood disease, it would be useful to calculate the relationship between the predicted and observed rates of erythropoietin as well as the transferin serum receptors.

Topics: Adult; Anemia, Aplastic; Animals; Child; Erythropoiesis; Erythropoietin; Female; Humans; Male; Mice; Mice, Transgenic; Neoplasms; Pregnancy; Receptors, Transferrin; Recombinant Proteins; Red-Cell Aplasia, Pure; Treatment Outcome

IMPROVED QUALITY OF LIFE WITH EPOETIN BETA: In a study against a placebo, there was evidence that the quality of life scores were significantly improved in patients treated with epoetin beta, whether they exhibited a solid tumour or a malignant lymphoma. The same was noted in children with cancer exhibiting severe neoplasia and treated with chemotherapy. The efficacy and tolerance to treatment were equivalent, whatever the administration regimen. IN PATIENTS SUFFERING FROM MYELODYSPLASTIC SYNDROMES: A particular entity among malignant blood diseases, myelodysplastic syndromes are at the origin of anaemia against which repeated transfusions and growth factors are proposed with varying results and disadvantages, and against which erythropoietin may be moderately effective (a mean of 25% in non-selected cohorts of patients). DEPENDING ON THE PROTOCOLS OF ERYTHROPOIETIN ADMINISTRATION IN CASES OF MYELODYSPLASTIC SYNDROMES: Recombinant human erythropoietin, irrespective of its concentration in myelodysplastic cell culture, does not appear capable of restoring normal erythropoiesis. The influence of prolonged treatment is not admitted by all. The effects of the addition of growth factors (notably G-CSF) are obvious but some are controversial because of the costs and the prolonged duration of such treatments.

Topics: Adult; Anemia, Aplastic; Blood Transfusion; Child; Erythropoiesis; Erythropoietin; Hemoglobinometry; Humans; Myelodysplastic Syndromes; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Red-Cell Aplasia, Pure; Treatment Outcome

THE DEBATE: Although some believe that rHu-EPO should not be widely used in malignant affections, others think that because of the varied impact of these anaemia, its wider use should be recommended. FOR A TARGET USE: Various observations (influence of the degree of extension of the myelomas to the skeleton and response to specific treatment in the case of myeloma, whatever the haemoglobin concentration, degree of prevention of rHu-EPO chemo-induced anaemia) are in favour of its use in selected patients. FOR A WIDER USE: The benefits of treatment with rHu-EPO are not limited to the symptomatology of anaemia but extend to its potential complications in the most fragile patients. Other than the risks of infection, the heavy costs of transfusions must also be taken into account.

Topics: Anemia, Aplastic; Blood Transfusion; Cost-Benefit Analysis; Erythropoietin; Hemoglobinometry; Humans; Multiple Myeloma; Neoplasms; Prognosis; Recombinant Proteins; Red-Cell Aplasia, Pure

Topics: Anemia, Aplastic; Blood Transfusion; Erythropoietin; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Red-Cell Aplasia, Pure

Anemia is a multifactorial problem in patients with human immunodeficiency virus (HIV) infection, cancer, and hepatitis C virus (HCV) infection. New insights regarding anemia symptoms and quality of life (QOL) have prompted reassessment of traditional triggers for anemia treatment to increase hemoglobin (Hb) and improve QOL. In HIV-positive patients, anemia is independently associated with disease progression and survival. Many HIV-positive patients receiving highly active antiretroviral therapy (HAART) still develop mild to moderate anemia and associated QOL impairment. Epoetin alfa effectively increases Hb and improves QOL in these patients. Many HIV-positive patients are coinfected with HCV. Standard HCV therapy (interferon alfa/ribavirin) can cause anemia that may result in treatment alterations and compromised virologic outcome. Epoetin alfa therapy in anemic HCV patients increases Hb levels and may provide other benefits. Neuroprotective effects of epoetin alfa in preclinical models of central nervous system disorders have recently been demonstrated, implying a new therapeutic role for this cytokine.

Topics: Anemia; Central Nervous System Diseases; Epoetin Alfa; Erythropoietin; Hepacivirus; Hepatitis C; HIV; HIV Infections; Humans; Neoplasms; Recombinant Proteins

Anemia commonly occurs in patients with cancer or human immunodeficiency virus (HIV) infection as a result of the disease, its treatment, or both. The negative impact of anemia on patient quality of life (QOL), functional status, and treatment outcomes underscores the need for its correction in these patients. In anemic patients with cancer or HIV infection, treatment with epoetin alfa increases hemoglobin (Hb) levels, decreases transfusion requirements, and improves QOL. In both settings, the gains in overall QOL have been significantly and directly related to increases in Hb, with maximum QOL gains in the range of Hb levels of 11-13 g/dL, supporting the need to achieve and maintain Hb levels > or =12 g/dL in an effort to preserve and maximize QOL benefits. A potential survival benefit has also been associated with correction of anemia in patients with HIV infection--and possibly in those with cancer as well.

Topics: Anemia; Clinical Trials as Topic; Disease Progression; Epoetin Alfa; Erythropoietin; HIV; HIV Infections; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Topics: Anemia; Breast Neoplasms; Cell Division; Erythropoietin; Female; Humans; Male; Neoplasms; Neovascularization, Pathologic; Receptors, Erythropoietin; Recombinant Proteins

Previous trials of recombinant human erythropoietin (rHuEpo) therapy after autologous hematopoietic stem cell transplantation have administered very high doses of i.v. rHuEpo starting on day 1 and continuing for 1-2 months until erythroid engraftment and have shown no benefit of rHuEpo therapy. We sought to establish a more effective use of rHuEpo in this setting.. In this report, we show in a first cohort of 45 lymphoma or myeloma patients undergoing peripheral blood stem cell transplant (control group) that endogenous erythropoietin levels are high for the degree of anemia during the first 3 weeks after transplant but become adequate or slightly decreased thereafter. We thus enrolled 41 consecutive similar patients in a trial of rHuEpo therapy at a dose of 500 units/kg/week started on day 30 after the transplant.. The 12-week probability of achieving hemoglobin (Hb) levels of 13 g/dl was 87% in rHuEpo-treated patients versus 14% in controls (P = 0.0001). Mean Hb levels were significantly higher in the rHuEpo group than in the control group from day 42 through day 150 after transplant (Ps of <0.05 to <0.001). Two of 41 patients in the rHuEpo group versus 12 of 45 patients in the control group had Hb levels of <9 g/dl between day 42 and day 100 after the transplant (P = 0.0078).. Anemia after autologous peripheral blood stem cell transplant is exquisitely sensitive to rHuEpo when therapy is started soon after engraftment. This is the first convincing report showing that rHuEpo is effective in this setting. Our data set the stage for a more rational use of rHuEpo after autologous hematopoietic stem cell transplantation and should renew interest in erythropoietin therapy in this setting. Prospective, randomized trials should investigate the impact of rHuEpo therapy on transfusion requirements and quality of life.

Topics: Adolescent; Adult; Aged; Anemia; Blood Transfusion; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms; Recombinant Proteins; Stem Cell Transplantation; Time Factors; Transplantation, Autologous

Topics: Antibodies, Monoclonal; Apoptosis; Cell Membrane Permeability; Drug Delivery Systems; Drug Therapy, Combination; Erythropoietin; Humans; Neoplasms; ras Proteins; Receptor, ErbB-2; Recombinant Proteins; Signal Transduction

Topics: Anemia; Antineoplastic Agents; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Neovascularization, Pathologic; Recombinant Proteins

Darbepoetin alfa is the second erythropoietic protein to be approved for the treatment of chemotherapy-induced anemia (CIA). In the clinical setting, darbepoetin alfa can be administered less frequently than epoetin alfa with similar efficacy. Practice patterns and outcomes associated with the use of darbepoetin alfa and epoetin alfa in the clinical setting have not been reported.. This study compared practice patterns and clinical outcomes of the use of darbepoetin alfa and epoetin alfa for CIA at oncology practices in the United States.. This was a multicenter retrospective cohort study. Data were abstracted from the medical charts of consecutive patients who began darbepoetin alfa treatment between August 1 and October 4, 2002, or epoetin alfa treatment between April 1 and July 31, 2002, and were receiving concurrent chemotherapy. These data were used to determine the initial dose and dosing schedule, dose changes, and changes in hemoglobin concentrations after 4, 8, and 12 weeks of treatment, adjusted for red blood cell (RBC) transfusions, and the incidence of RBC transfusions over time. To minimize potential bias, the study protocol defined specific end points and prespecified analytic techniques for assessing clinical outcomes with the 2 agents.. The records of 1391 patients from 16 community and hospital outpatient oncology clinics were abstracted. Of these, 1293 patients (93.0%) received only 1 erythropoietic agent (darbepoetin alfa, 735 [56.8%]; epoetin alfa, 558 [43.2%]); the remainder received both agents. In the patients who received darbepoetin alfa, most (553 [75.2%]) received an initial dosage of 200 microg q2wk. A similar proportion (414 [74.2%]) received epoetin alfa at an initial dosage of 40,000 U qwk. As these were the regimens for the majority of patients whose records were abstracted, the results reported here are for these patients. The dose was increased in 63 darbepoetin alfa recipients (11.4%) and 58 epoetin alfa recipients (14.0%) at a median of 7 weeks. After 12 weeks, the 2 groups had an identical mean imputed change from baseline in hemoglobin concentration (1.0 g/dL), and the incidence of RBC transfusions during treatment was also similar between groups (darbepoetin alfa, 44553 [8.0%]; epoetin alfa, 39414 [9.4%]).. Darbepoetin alfa 200 microg q2wk was used as a standard regimen for CIA at the 16 US oncology practices participating in this study. It appeared to be as effective as epoetin alfa 40,000 U qwk, with a reduced frequency of dosing.

Topics: Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Darbepoetin alfa; Drug Administration Schedule; Drug Utilization Review; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Practice Patterns, Physicians'; Recombinant Proteins; Retrospective Studies

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase III as Topic; Darbepoetin alfa; Erythropoiesis; Erythropoietin; Humans; Lung Neoplasms; Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Reproducibility of Results; Treatment Outcome

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Child; Child Welfare; Erythropoietin; Humans; Neoplasms

Anemia occurs frequently in children with cancer, but there is little information quantifying the incidence of anemia or treatment. A survey was conducted in 1998 in Europe by The Research Partnership with the objective of determining the incidence of anemia, identifying the hemoglobin triggers that initiated anemia treatment, and the current anemia treatment options available to clinicians.. The survey was conducted in the 10 largest pediatric oncology centers each in France, Germany, Italy, Spain, and the UK, and in the 8 largest centers in both Belgium and The Netherlands. Telephone interviews with the most senior physician available in the institution were used to collect data, which included the numbers of patients treated or under follow-up, cancer types, and treatment practices for anemia.. Data were collected for 25,093 patients. Over 80% of patients were anemic (WHO: hemoglobin

Topics: Adolescent; Anemia; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Epoetin Alfa; Erythropoietin; Europe; Female; Health Surveys; Hematinics; Humans; Incidence; Infant; Infant, Newborn; Male; Neoplasms; Recombinant Proteins

Anemia resulting from cancer or its treatment is an important clinical problem increasingly treated with the recombinant hematopoietic growth factor erythropoietin. To address uncertainties regarding indications and efficacy, the American Society of Clinical Oncology and the American Society of Hematology developed an evidence-based clinical practice guideline for the use of epoetin in patients with cancer. The guideline panel found good evidence to recommend use of epoetin as a treatment option for patients with chemotherapy-associated anemia with a hemoglobin (Hgb) concentration below 10 g/dL. Use of epoetin for patients with less severe anemia (Hgb level below 12 g/dL but never below 10 g/dL) should be determined by clinical circumstances. Good evidence from clinical trials supports the use of subcutaneous epoetin thrice weekly (150 U/kg) for a minimum of 4 weeks. Less strong evidence supports an alternative weekly (40 000 U/wk) dosing regimen, based on common clinical practice. With either administration schedule, dose escalation should be considered for those not responding to the initial dose. In the absence of response, continuing epoetin beyond 6-8 weeks does not appear to be beneficial. Epoetin should be titrated once the hemoglobin concentration reaches 12 g/dL. Evidence from one randomized controlled trial supports use of epoetin for patients with anemia associated with low-risk myelodysplasia not receiving chemotherapy; however, there are no published high-quality studies to support its use for anemia in other hematologic malignancies in the absence of chemotherapy. Therefore, for anemic patients with hematologic malignancies it is recommended that physicians initiate conventional therapy and observe hematologic response before considering use of epoetin.

Topics: Anemia; Clinical Trials as Topic; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Evidence-Based Medicine; Hematinics; Humans; Neoplasms; Quality Assurance, Health Care; Recombinant Proteins

Anemia resulting from cancer, or its treatment, is an important clinical problem increasingly treated with the recombinant hematopoietic growth factor erythropoietin. To address uncertainties regarding indications and efficacy, the American Society of Clinical Oncology and the American Society of Hematology developed an evidence-based clinical practice guideline for the use of epoetin in patients with cancer. The guideline panel found good evidence to recommend use of epoetin as a treatment option for patients with chemotherapy-associated anemia with a hemoglobin level less than 10 g/dL. Use of epoetin for patients with less severe anemia (hemoglobin < 12 g/dL but never below 10 g/dL) should be determined by clinical circumstances. Good evidence from clinical trials supports the use of subcutaneous epoetin thrice weekly (150 U/kg tiw) for a minimum of 4 weeks. Less strong evidence supports an alternative weekly (40,000 U/wk) dosing regimen, based on common clinical practice. With either administration schedule, dose escalation should be considered for those not responding to the initial dose. In the absence of response, continuing epoetin beyond 6 to 8 weeks does not appear to be beneficial. Epoetin should be titrated once the hemoglobin concentration reaches 12 g/dL. Evidence from one randomized controlled trial supports use of epoetin for patients with anemia associated with low-risk myelodysplasia not receiving chemotherapy; however, there are no published high-quality studies to support its use for anemia in other hematologic malignancies in the absence of chemotherapy. Therefore, for anemic patients with hematologic malignancies, it is recommended that physicians initiate conventional therapy and observe hematologic response before considering use of epoetin.

Topics: Anemia; Erythropoietin; Evidence-Based Medicine; Humans; Neoplasms; Practice Guidelines as Topic; Societies, Medical

Topics: Anemia; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Research Design

Myelosuppression is a common side effect in elderly patients undergoing chemotherapy. Neutropenia and anemia cause considerable morbidity, may increase mortality, and can result in a worse outcome of treatment in elderly patients compared to younger patients with comparable type and stage of disease. The availability and proven efficacy of hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO) have had a considerable impact on supportive care in cancer patients: Several randomized trials have demonstrated a reduction of neutropenia and the frequency of severe infections in elderly patients treated with G-CSF following myelotoxic chemotherapy compared with patients without growth factor support. Both for G-CSF and for recombinant human erythropoietin (rHu-EPO) several studies have demonstrated the safety and effectiveness of these molecules in elderly patients with regard to increasing hemoglobin concentrations, improving quality of life (rHu-EPO), and neutrophil recovery. Although a positive effect of the use of growth factors on overall survival in elderly cancer patients is not yet proven, a reduction of chemotherapy-induced side effects could clearly be shown. The National Comprehensive Cancer Network (NCCN) of cancer centers has recommended that all patients aged 70 years and older treated with CHOP or cytotoxic chemotherapy of comparable intensity should receive prophylactic G-CSF administration, and that the hemoglobin concentration be maintained at >or=12 g/dl in elderly patients undergoing chemotherapy.

Topics: Aged; Anemia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Neoplasms; Neutropenia; Prednisone; Recombinant Proteins; Vincristine

(1) The standard treatment for symptomatic anaemia due to cytotoxic chemotherapy is blood transfusion. (2) The licensing terms for epoetin alfa have been extended to cover the treatment of anaemia induced by all cytotoxic drugs, no longer only by platinum salts. The licensing terms for epoetin beta have been extended to cover some haematological malignancies. (3) The clinical file on epoetin alfa contains data from 8 placebo-controlled double-blind trials in patients with anaemia. Four trials showed a significant reduction (of 12-35%) in the number of patients transfused during the second and third months of treatment with epoetin alfa. (4) Quality of life was mentioned in only two trial reports. In one, the score was significantly better on epoetin alfa than on placebo, but the practical repercussions of this difference are unclear. In the other trial there was no significant difference between the groups. (5) The clinical file on epoetin beta contains data only from unblended dose-finding studies showing a favourable impact on the haemoglobin level and transfusion requirements. (6) The preventive effect of the two epoetins has not been compared with that of alternative treatments. (7) The main known risks of epoetin are arterial hypertension and thrombosis. Stimulation of tumour growth cannot be ruled out. (8) Epoetin beta has a practical advantage, in that it can be stored for a few days at room temperature. (9) In practice, epoetin is the standard treatment of anaemia after chemotherapy, outside emergency situations.

Topics: Anemia; Clinical Trials as Topic; Drug Approval; Epoetin Alfa; Erythropoietin; France; Hematinics; Humans; Neoplasms; Recombinant Proteins

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Research Design

Evaluation of the mechanism of anemia in cancer patients might help to select patients for the more efficient use of erythropoietin (EPO, a growth factor for erythroid precursor cells). For this, we investigated whether the production of EPO responds to anemia and the bone marrow responds to EPO appropriately, and whether chronic inflammation is inhibitory to erythropoiesis in anemic cancer children. Serum levels of EPO, soluble transferrin receptor (sTfR), tumor necrosis factor (TNF)-alpha, and erythrocyte sedimentation rate (ESR) in anemic cancer children were measured by enzyme-linked immunosorbent assay and then the correlation coefficients between those parameters and hemoglobin (Hb) were determined. Both in leukemia and in solid tumor patients, there were significant inverse correlations between Hb and EPO (leukemia: tau=-0.547, p<0.0001; solid tumor: tau=-0.591, p<0.0001), and between sTfR and EPO (leukemia: tau=-0.223, p<0.05; solid tumor: tau=-0.401, p<0.05). In contrast, sTfR showed a correlation with Hb in leukemia (tau=0.216, p<0.05) but not in solid tumor patients. sTfR was suppressed in 53% of anemic episodes of leukemia and 78% of those of solid tumor patients. Our results suggest that in cancer children, the EPO production is not defective and chronic inflammation is not inhibitory to erythropoiesis. Rather, the defective erythropoiesis itself is thought to be responsible for the anemia.

Topics: Anemia; Blood Sedimentation; Bone Marrow; Child; Erythropoiesis; Erythropoietin; Female; Humans; Male; Neoplasms; Receptors, Transferrin; Solubility; Tumor Necrosis Factor-alpha

Topics: Anemia; Blood Transfusion; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Medical Oncology; Neoplasms; Practice Guidelines as Topic; Quality of Life; Recombinant Proteins; United States; United States Agency for Healthcare Research and Quality

Topics: Anemia; Clinical Trials as Topic; Darbepoetin alfa; Drug Evaluation, Preclinical; Erythropoietin; Half-Life; Humans; Neoplasms; Recombinant Proteins

Topics: Anemia, Hemolytic; Antineoplastic Agents; Bone Marrow Purging; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Humans; Incidence; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Treatment Outcome

Topics: Blood Donors; Blood Transfusion, Autologous; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Fees, Pharmaceutical; Hematinics; HIV Infections; Hypertension, Renal; Neoplasms; Premedication; Preoperative Care; Recombinant Proteins; Renal Insufficiency

The debate on rationalisation vs. rationing of health care interventions is of great importance for the shaping of social and health care policies. Nevertheless, concrete evaluations mostly deal with health interventions in the grey zone between rationing--withholding effective measures--and rationalisation--avoiding ineffective interventions. The assessment of erythropoietin in tumour anaemia is presented as an example: the results of the treatment of tumour-induced anaemia with EPO are partly unsatisfactory. Only 50-60% of anemic tumor-patients respond to EPO; of these responders 20-30% still require transfusions. The assessment presents the evidence for an "appropriate" application of erythropoietin in tumour anaemia and proposes standard values for a limited access and use of EPO. Additionally the assessment reveals what is known as the benefit of this treatment, and what is questionable. Applying the results of the assessment to clinical practice can be considered as "explicit rationing" according to effectiveness criteria.

Topics: Anemia; Cost-Benefit Analysis; Erythropoietin; Germany; Health Care Rationing; Health Policy; Humans; National Health Programs; Neoplasms; Rationalization

Topics: Animals; Erythropoiesis; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

Recently, recombinant human erythropoietin (rhEPO) was introduced for the management of anemia in malignancy. To identify an indicator for a favourable response to rhEPO, 28 anaemic cancer patients undergoing chemotherapy and treated with rhEPO were evaluated.. Patients were classified into responder (16 of 28, 57%) and nonresponder (12 of 28, 43%) groups according to their responses to rhEPO therapy (response being defined as an increase in Hb level of > 2 g/dl from baseline without blood transfusion).. Treatment with rhEPO showed significant improvements in the red blood cell (RBC) count, haemoglobin (Hb), packed cell volume (PCV), and reticulocyte count (ret. count) after 4 weeks. Upon analysing the baseline value of the EPO level and the corrected ret.count in these two groups, we found that the ratio of the EPO level and the corrected ret.count (EPO/ret.count) demonstrated a statistical significance (P = 0.03) in the prediction of response to rhEPO therapy. This ratio showed a sensitivity of 87.5%, specificity of 66.7%, and overall accuracy of 78.6%.. Our study suggested that the baseline ratio of EPO/ret.count should be used as an indicator for a favourable response to rhEPO therapy.

Topics: Adult; Aged; Anemia; Erythrocyte Indices; Erythrocytes; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Prognosis; Recombinant Proteins; Reticulocyte Count

Topics: Anemia; Blood Transfusion; Clinical Trials as Topic; Erythropoietin; Humans; Neoplasms; Outcome Assessment, Health Care; Practice Guidelines as Topic; Recombinant Proteins

The level of serum erythropoietin (EPO) is inappropriately decreased in cancer patients and has been advocated as the main cause of their anemia. In cancer patients, chemotherapy results in a cumulative anemia severe enough to require transfusion. We investigated the changes in serum EPO, hemoglobin, ceruloplasmin, and copper levels in cancer patients receiving chemotherapy. There was a weak but significant inverse relationship between hemoglobin and log[EPO] (r = -0.41; P < .001). Observed/expected serum EPO ratios decline with repeated chemotherapy indicating inadequate EPO response for the degree of anemia. There was no difference in the severity of anemia and in the degree of EPO response between platinum- and non-platinum-treated patients. Ceruloplasmin, copper, and ferritin levels did not change during chemotherapy. Our results suggest that the EPO response is inadequate for the degree of anemia and justifies the use of recombinant human EPO in cancer patients receiving chemotherapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Anemia; Antineoplastic Agents; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms

Anaemia is a common complication of cancer and cancer therapies, and fatigue is one of the most common symptoms of anaemia, disrupting functional performance and reducing overall quality of life. The positive effects of treating renal patients with recombinant human erythropoietin are well documented. This case report series details the specific effects of fatigue on individual patients with cancer and their way of life, and describes their significant improvement in lifestyle following the reversal of anaemia using recombinant human erythropoietin, epoetin alfa.

Topics: Aged; Anemia; Epoetin Alfa; Erythropoietin; Fatal Outcome; Female; Hematinics; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins

Topics: Erythropoietin; Humans; Neoplasms

Anemia is a frequent complication of cancer and its treatment. A defect in erythropoietin production has been advocated as being the main cause of anemia in cancer patients. We studied serum erythropoietin levels in 74 patients with solid tumors and in a control group consisting of 20 otherwise healthy individuals without any malignancy, who have only iron deficiency anemia. Serum erythropoietin levels were measured by enzyme immunoassay in cancer patients without anemia (n=34), and in anemic cancer patients (n=40); either receiving chemotherapy (n=21) or not (n=19). Anemic cancer patients were found to have decreased response of erythropoietin for a given hemoglobin level (mean, 40.1+/-34.7 u/ml), compared with the patients having only iron deficiency anemia (mean, 69.7+/-68.6 u/ml) (P<0.05). In patients with iron deficiency anemia having no malignancy, erythropoietin response was remarkably high and inversely correlated with the level of hemoglobin (r=-0.69; P=0. 05). Although there was no correlation between hemoglobin and erythropoietin response in cancer anemia (r=-0.07), serum levels of erythropoietin were found to be higher in anemic cancer patients (mean, 40.1+/-34.7 u/ml), compared with cancer patients with normal hemoglobin values (mean, 19.96+/-18.4 u/ml). There was not any statistically significant difference between erythropoietin levels in anemic cancer patients with or without chemotherapy (mean, 43. 7+/-37.7 u/ml and 41.9+/-30.08 u/ml respectively; P>0.05). No difference in serum erythropoietin levels were noted in patients treated with cisplatin or non-cisplatin containing regimens (mean, 48.36+/-33.12 u/ml and 38.55+/-43.52 u/ml, respectively; P>0.05). In this study, we demonstrated that anemia in cancer patients was caused by blunted erythropoietin response, rather than its quantitative deficiency. Serial measurements, however, should be considered in patients receiving chemotherapy.

Topics: Adolescent; Adult; Aged; Anemia; Anemia, Iron-Deficiency; Antineoplastic Combined Chemotherapy Protocols; Case-Control Studies; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms

Topics: Anemia, Hypochromic; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Erythropoietin; Female; Hemoglobins; Humans; Male; Neoplasms; Recombinant Proteins; Treatment Outcome

Topics: Anemia; Antineoplastic Agents; Cost-Benefit Analysis; Erythrocyte Transfusion; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Treatment Failure

Topics: Aged; Anemia; Antineoplastic Agents; Blood Transfusion; Epoetin Alfa; Erythropoietin; Europe; Evidence-Based Medicine; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Practice Patterns, Physicians'; Quality of Life; Recombinant Proteins; Treatment Outcome; United States

Topics: Anxiety; Consumer Product Safety; Drug Industry; Erythropoietin; False Positive Reactions; Fatigue; Humans; Marketing of Health Services; Mass Screening; Neoplasms; Prostate-Specific Antigen; United States; United States Food and Drug Administration; Vaginal Smears

Platinum chemotherapy has been shown to have potent antineoplastic activity against various tumours, especially testicular, bladder, ovarian, head and neck cancers. This activity is accompanied by side-effects of nephrotoxicity and cumulative myelosuppression, the latter frequently presenting as severe anaemia. Cisplatin and carboplatin nephrotoxicity might lower erythropoietin (Epo) secretion and, by this mechanism, contribute to the anaemia that follows therapy with this chemotherapeutic agent. The aim of the present work is to study the plasma immunoerythropoietin and haemoglobin levels of cancer patients treated with platinum or 5-fluorouracil-based chemotherapy.. Plasma was obtained from 25 patients who were about to receive chemotherapy for advanced malignancy: 15 treated with cisplatin or carboplatin and 10 with nonplatinum drugs. Blood was collected on the first day (before drug administration) and around day 15 of every chemotherapy course. Complete blood count, creatinine and immunoreactive Epo levels were also measured in 22 healthy volunteers.. An increase in Epo levels occurred following every course of 5-FU or platinum based chemotherapy in patients with steady concentrations of creatinine and decreased levels of haemoglobin (Hb). In particular, we observed an increase after about 15 days of the chemotherapy treatment and the Epo levels declined toward normal just before the following course. This phenomenon was evident in every course.. Our results suggest that chemotherapy administration, using the current standards of hydration and forced diuresis, slightly lowered Hb levels but did not depress Epo production, both in 5-FU and in platinum treated subjects.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cisplatin; Colorectal Neoplasms; Erythropoietin; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasms

At the recent EHA meeting in Birmingham, UK, an expert audience of haematologists and oncologists were polled using keypad technology on current thinking and treatment practices in anaemia in cancer patients. More than 76% of the audience thought that anaemia had a significant negative impact on the quality of life of cancer patients. The majority (> 60%) would institute treatment on the basis of appropriate symptoms rather than haemoglobin level, although among those who would use haemoglobin levels, there was no consensus on the concentration at which they would start treatment. The majority of respondents (54%) chose not to use the serum erythropoietin level as a guide as to when to institute therapy with recombinant human erythropoietin (rHuEPO) but, of those who would use it, 55% would use onlythe haemoglobin or haematocritto identify those responding within thefirst 2-4weeks of treatment. The remainder of the session used three case studies to investigate current treatment practices.

Topics: Anemia; Attitude of Health Personnel; Erythropoietin; Health Care Surveys; Hemoglobins; Humans; Neoplasms; Practice Patterns, Physicians'; Quality of Life; Recombinant Proteins

Topics: Anemia; Antineoplastic Agents; Child; Child, Preschool; Epoetin Alfa; Erythropoietin; Humans; Infant; Infant, Newborn; Infant, Premature; Iron; Kidney Failure, Chronic; Neoplasms; Radiotherapy; Recombinant Proteins

This study analyses the factors affecting mobilisation and engraftment in autologous peripheral blood progenitor cell transplantation according to the number of CD34(+) re-infused.. A total of 190 patients underwent mobilisation with G-CSF alone (n=113) or in combination with chemotherapy (n=77). A total of 116 patients (61%) were autografted with <2 x 10(6) CD34(+) cells/kg and 74 patients were transplanted with >2 x 10(6) CD34(+) cells/kg. Rates of granulocyte and platelet recovery were estimated using the product-limit method of Kaplan-Meier and compared using a log-rank test. The Cox regression model was used for the multivariate analysis of factors influencing engraftment. Differences between cohorts were evaluated by one-way ANOVA or Mann-Whitney tests, and multivariate analysis was performed using a stepwise lineal regression.. Neutrophil and platelet engraftment was significantly longer with <2 x 10(6)/CD34(+)/kg (12 vs 10 days, P=0.014 and 16 vs 13 days, P=0.0001 respectively). Platelet recovery was affected by exposure to alkylating agents (P=0.04), refractory disease (P=0.02) and AML (P=0.0001), but only the last two variables remained significant in Cox regression (P<0.01). Granulocyte engraftment was longer in CML (univariate, P=0.04) and in refractory disease (multivariate, P=0.02). In patients re-infused with >2 x 10(6)/CD34(+)/kg, the Cox model did not identify prognostic factors for haematopoietic recovery.. Although mobilisation schedules and disease status influenced not only the yield of progenitor cells, but also the engraftment kinetics, the number of CD34(+) re-infused was the main predictor of haematopoietic recovery. While engraftment succeeded in most of the cases, the re-infusion of >2 x 10(6)/CD34(+)/kg resulted in significantly shorter recovery times.

Topics: Adolescent; Adult; Aged; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Blood Cell Count; Caspase 14; Caspases; Cerebral Hemorrhage; Cohort Studies; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Erythropoietin; Etoposide; Female; Graft Survival; Granulocyte Colony-Stimulating Factor; Hematologic Neoplasms; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Hydroxyurea; Infections; Leukapheresis; Life Tables; Male; Middle Aged; Neoplasms; Proportional Hazards Models; Transplantation Conditioning; Transplantation, Autologous

Although the recombinant granulocyte colony-stimulating factor (G-CSF) is a good CD34 cell mobilizer, the effects of G-CSF mobilization on the immune effector function of the individual is not always optimal. We studied the functional and phenotypic properties of peripheral blood stem cells (PBSC) collected from 15 cancer patients mobilized with G-CSF plus recombinant erythropoietin (EPO).. The patients received EPO (300 U/kg) and (G-CSF 1 microg/kg) per day as mobilizing cytokines and an autologous graft product was collected with at least daily apheresis procedures until a target number of CD34 cells and mononuclear cells were obtained. Mononuclear cells from the first four PBSC collections were tested for their natural killer (NK), activated NK and lymphokine activated killer (LAK) cytotoxicity in vitro against K562 and Raji tumor target cells.. There was a significant increase in NK, activated NK and LAK cytotoxicity in EPO + G-CSF mobilized cells when compared to mononuclear cells from premobilization blood baseline values. Although there was no increase in CD3+ T cells, there was a significant increase in myeloid cells (CD14+), B-cells (CD20+) and NK cells (CD56+) following mobilization. There was no difference in T cell response to the mitogens PHA and Con-A, but there was an increase in B-cell response to PWM following mobilization. Thus, the combination of EPO + G-CSF not only mobilized hematopoietic precursor cells but also increased the number of immune effector cells in the PBSC collections.

Topics: Adult; Blood Component Removal; Cell Division; Cell Size; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells; Humans; Immunophenotyping; Killer Cells, Lymphokine-Activated; Killer Cells, Natural; Leukocytes, Mononuclear; Male; Middle Aged; Mitogens; Neoplasms; Tumor Cells, Cultured

Parvovirus B19 is the only member of the Parvoviridae family known to cause disease in humans. Owing to the high level of cell tropism the virus can only replicate in proliferating and differentiating erythroid precursor cells, which are present in human bone marrow and foetal liver. As human bone marrow is very difficult to obtain, an alternative in vitro system for the propagation of B19 virus has been developed, based on the application of mobilized haemapoietic progenitor (apheresis) cells. These cells are routinely harvested from cancer patients after treatment with recombinant human granulocyte/macrophage colony-stimulating factor. Replication of parvovirus B19 in vitro is possible in these cells after stimulation with erythropoietin. Therefore, this system is an easily, accessible alternative to the use of human bone marrow in parvovirus B19 infection assays.

Topics: Blood Component Removal; Blotting, Southern; DNA Replication; DNA, Viral; Erythropoietin; Genome, Viral; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells; Humans; Leukocytes, Mononuclear; Neoplasms; Parvovirus; Recombinant Proteins; Tumor Cells, Cultured; Virus Cultivation

Topics: Erythropoietin; Hemoglobinometry; Hemoglobins; Humans; Hypoxia; Neoplasms; Oxygen

Topics: Bone Neoplasms; Breast Neoplasms; Combined Modality Therapy; Diphosphonates; Erythropoietin; Female; Humans; Male; Neoplasm Metastasis; Neoplasms; Pilot Projects; Radiotherapy

Topics: Anemia; Antineoplastic Agents; Cost-Benefit Analysis; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Cancer is often associated with chronic anemia which frequently requires blood transfusions. This study was performed to assess the efficacy and safety of r-HuEPO therapy in children with cancer.. Twenty-five patients under 18 years of age with solid malignant tumors were treated with 150 U/kg/day of r-HuEPO 5 times weekly for 12 weeks. Response was defined as an increase of the baseline hemoglobin level by at least 2 g/dl. r-HuEPO patients were compared to 25 matched historical controls.. Response was achieved in 72% of r-HuEPO patients. Hemoglobin level increased from 9.8 +/- 0.6 g/dl at baseline to 12.4 +/- 1.7 g/dl at the end of treatment in the r-HuEPO group and increased from 9.5 +/- 0.7 g/dl to 9.6 +/- 1.4 g/dl in the control group (P < .001, Student's t-test). Only 16% of patients receiving r-HuEPO required blood transfusions vs 96% of control patients (P < .001, Student's t-test), with mean units of blood transfused per patient being 0.35 in the r-HuEPO group and 3.56 in controls (P < .001, Student's t-test). There was a statistically significance improvement in Karnofsky's index in r-HuEPO patients. No adverse reaction related to r-HuEPO therapy was observed.. r-HuEPO is a safe and effective means of increasing hemoglobin level and reducing blood requirements in children with solid malignant tumors receiving chemotherapy.

Topics: Adolescent; Anemia; Child; Child, Preschool; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Male; Neoplasms; Recombinant Proteins

Epoetin alfa is being used to treat patients with symptomatic anemia of cancer and to prevent or postpone chemotherapy-induced anemia in cancer treatment. As only approximately 50% of unselected anemic cancer patients respond sufficiently to epoetin alfa treatment, careful patient selection according to reliable prediction criteria is of great importance. Predictions of response to epoetin alfa treatment are based either on the degree of blunted erythropoietin response to the anemic condition or on indicators of responsiveness during the early treatment phase. The most accurate predictions of responsiveness, however, are derived from combinations of predictive factors. Combinations of synergistically acting hematopoietic growth factors, particularly epoetin alfa and granulocyte colony-stimulating factor, are beneficial to selected patients with myelodysplastic syndrome and may prolong survival in certain cases. Correction of anemia in cancer patients is particularly important because highly significant correlations have been reported between hemoglobin levels and quality of life in these patients.

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Myelodysplastic Syndromes; Neoplasms; Patient Selection; Quality of Life; Recombinant Proteins

Even with the reservations that exist regarding the accuracy of tools to measure quality of life, there is little doubt that epoetin has dramatically improved the quality of life in patients with the anemia of chronic renal failure. Patients feel better and have increased energy levels, greater capacity for physical exercise, fewer symptoms of lethargy and tiredness, improved memory and concentration, and less angina and breathlessness. Cardiac, sexual, and cognitive functions all improve, and quality of life assessments suggest enhancements in both physical and social aspects of well-being. Furthermore, circumstantial evidence suggests that treatment with epoetin is quite likely to reduce cardiovascular morbidity and mortality in patients with renal anemia. While chronic anemia has common characteristics irrespective of the etiology, the implications on quality of life in patients with chronic renal failure vary in a number of ways from those in patients with cancer.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Neoplasms; Quality of Life; Recombinant Proteins

High-dose chemotherapy (HDCT) with bone marrow transplantation (BMT) is associated with the development of significant anemia. The anemia is caused mainly by myelosuppression, although gastrointestinal-, genitourinary-, and phlebotomy-induced blood loss may also contribute. The number of red blood cell units transfused during the first 30 days following HDCT depends on the chemotherapy used, the underlying disease, and whether BMT was allogeneic, autologous, and used either peripheral blood stem cell or bone marrow support. Epoetin alfa has been used to treat the anemia that develops in the HDCT setting. Controlled studies in patients with both hematologic malignancies and solid tumors who were given epoetin alfa following HDCT have shown that red blood cell transfusion requirements decrease in patients receiving allogeneic BMT. Results using epoetin alfa in patients receiving autologous BMT have been disappointing. Alternatively, combination therapy with granulocyte colony-stimulating factor and epoetin alfa has been effective in mobilizing stem cell and committed myeloid/erythroid precursors before HDCT, but has not resulted in a lower red blood cell transfusion requirement after HDCT. Administration of epoetin alfa before HDCT while the bone marrow is still responsive to growth factors may be a new strategy with which to decrease the anemia in this setting.

Topics: Anemia; Antineoplastic Agents; Bone Marrow Transplantation; Epoetin Alfa; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hematinics; Humans; Neoplasms; Recombinant Proteins

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Many investigators believe that cytokines have exclusive control over proliferation and differentiation in stroma-free hematopoietic cultures. Although cytokines are indeed necessary, other culture parameters such as oxygen (O2) tension can greatly influence both hematopoietic cell proliferation and differentiation. We investigated the effects of cytokine combinations and O2 tension on the expansion of megakaryocyte (size and number of CD41a+ cells and number of colony-forming units-megakaryocyte [CFU-Mk]), granulocyte (CD15+ cells and CFU-granulocyte monocyte [CFU-GM]), and erythrocyte (hemoglobin+ cells and burst-forming units-erythrocyte [BFU-E]) lineages. Peripheral blood CD34+ cells were cultured in serum-free medium with interleukin (IL)-3, stem cell factor (SCF), and various combinations of thrombopoietin (TPO), erythropoietin (EPO), and/or granulocyte-colony stimulating factor (G-CSF). The effects of TPO, EPO, and G-CSF on Mks, erythrocytes, and granulocytes, respectively, were dependent on the O2 tension. Thrombopoietin-containing cultures under a gas phase of 20%) O2 tension produced 1.4- to 2.2-fold more Mks than those under 5% O2. The increase in Mk size with TPO was also much greater under 20% O2. Similarly, 2.1- to 2.4-fold more hemoglobin-containing cells were produced in EPO-containing cultures under 20% vs. 5% O2. In contrast, approximately twice as many CD15+ cells were produced in G-CSF-containing cultures under 5% vs. 20%) O2. The numbers of CFU-Mk in TPO-containing and CFU-GM in G-CSF-containing cultures were larger under 5% O2. Although the O2 tension had no effect on BFU-E production in EPO-containing cultures, BFU-E production under 5% O2 in cultures without EPO was equal to that in EPO-containing cultures. Our data also suggest that TPO, EPO, and G-CSF elicit stimulatory cross-lineage effects in the presence of IL-3 and SCF, and that these effects, too, are often dependent on O2 tension.

Topics: Cell Count; Cell Division; Cell Lineage; Cells, Cultured; Culture Media, Serum-Free; Cytokines; Drug Interactions; Erythrocytes; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocytes; Hematopoiesis; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells; Humans; Interleukin-3; Megakaryocytes; Neoplasms; Oxygen; Partial Pressure; Stem Cell Factor; Thrombopoietin

A defect in erythropoietin (EPO) production has been advocated as being the main cause of anemia presented at time of diagnosis or during treatment by adults with solid tumors. On the basis of this defect, anemic cancer patients, both adults and children, have been treated with recombinant human EPO (rHuEPO). To further elucidate the pathophysiology of anemia in children with cancer, we measured serum soluble transferrin receptor (sTfR), a quantitative marker of erythropoiesis, and serum EPO at time of diagnosis and during chemotherapy in children suffering from solid tumor or leukemia. We determined serum EPO in 111 children (55 leukemia, 56 solid tumors) at time of diagnosis. In the last 44 patients (23 leukemia and 21 solid tumors), sTfR levels were also measured. Serum EPO together with sTfR levels were also determined in 60 children receiving chemotherapy (29 leukemia, 31 solid tumors). These results were compared with those obtained from appropriate control groups. In all patients, we found a highly significant correlation between the logarithm of EPO (log[EPO]) and the hemoglobin (Hb) level. In all subsets of patients, sTfR levels were inappropriately low for the degree of anemia. Neither leukemic nor solid tumor groups showed a significant inverse relationship between log(sTfR) and the Hb level as would be expected in anemic patients with appropriate marrow response. Thus, in children with cancer, anemia is associated with a decreased total bone marrow erythropoietic activity which, in contrast to what has been reported in anemic cancer adults, is not related to defective EPO production.

Topics: Adolescent; Anemia; Bone Marrow Cells; Child; Child, Preschool; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Female; Hemoglobins; Humans; Infant; Leukemia; Male; Neoplasms; Receptors, Transferrin

Topics: Anemia; Antineoplastic Agents; Cisplatin; Erythropoietin; Humans; Kidney Tubules; Neoplasms

To evaluate prospectively the effectiveness of epoetin alfa as an adjunct to chemotherapy in patients with cancer based on changes in quality-of-life parameters and hemoglobin levels, and to correlate these changes with antitumor response.. Two thousand three hundred seventy patients with nonmyeloid malignancies who received chemotherapy were enrolled onto this study from 621 US community-based practices. Patients received epoetin alfa 10,000 U three times weekly, which could be increased to 20,000 U three times weekly depending on the hemoglobin response at 4 weeks. Treatment continued for a maximum of 16 weeks in patients who showed evidence of hematologic response.. Two thousand two hundred eighty-nine patients (97%) were eligible for efficacy analyses. Epoetin alfa therapy was associated with improved quality-of-life parameters; these improvements correlated significantly with hemoglobin levels and were independent of tumor response. Provider-reported Karnofsky performance scores did not correlate with the improved quality-of-life changes. Epoetin alfa therapy was also associated with a significant increase in hemoglobin levels and decrease in transfusion use. Tumor type, chemotherapy agent/regimen, prior chemotherapy, baseline hemoglobin level, and baseline erythropoietin level were not predictive of a positive response to treatment. Epoetin alfa was well tolerated.. Epoetin alfa appears to have a beneficial impact on patient-reported functional capacity and quality of life in patients with cancer who received chemotherapy independent of tumor response. Concordantly, epoetin alfa appeared to increase hemoglobin levels and decrease transfusion use. Patients responded across all tumor types. The results suggest that epoetin alfa effectively improves functional outcomes in patients with cancer who receive chemotherapy.

Topics: Aged; Blood Transfusion; Drug Administration Schedule; Drug Resistance; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobin A; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Quality of Life; Recombinant Proteins; Sex Factors

Topics: Anemia; Erythropoietin; Humans; Neoplasms; Recombinant Proteins; Renal Insufficiency

Topics: Anemia; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Topics: Aged; Anemia; Erythropoietin; Humans; Middle Aged; Neoplasms; Recombinant Proteins

Advanced cancer is commonly associated with significant anemia which worsens with the administration of cytotoxic drugs. Erythropoietin (EPO) levels in these patients are usually inappropriately low for the degree of anemia. We evaluated the effect of subcutaneous administration of recombinant human erythropoietin (r-HuEPO) on hematologic parameters and transfusion requirements in anemic cancer patients who were receiving platinum-based chemotherapy. Baseline studies included complete hemogram, reticulocyte count, serum iron, TIBC, ferritin and determination of performance status and quality of life (QOL). Twenty-three patients, 13 females, 10 males with mean age 52 years received 150 units/kg of r-HuEPO three times weekly for a minimum of 10 weeks. They also received supplemental iron. Ovarian cancer was the commonest underlying malignancy. Most of the patients received platinum-based combination chemotherapy. Mean duration of r-HuEPO therapy was 12.6 weeks. Average baseline reticulocyte count was 1.8% which increased to 7.0% after one week therapy. Eight patients had normalization of hemoglobin values. Another eight patients improved their hemoglobin by at least 2 g/dl, however, hemoglobin values remained below the normal range. Two patients had only slight increase in hemoglobin but never required blood transfusion. Three patients who were transfusion dependent had decrease in the transfusion requirements. Two patients had no significant benefit. In most patients response was evident within 2 weeks. All responders had improvement in QOL. No significant toxicity was observed. We conclude that r-HuEPO, given subcutaneously, is highly effective in amelioration of anemia and prevention of or reduction in transfusion requirements in cancer patients receiving platinum-based chemotherapy.

Topics: Activities of Daily Living; Anemia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Cisplatin; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Injections, Subcutaneous; Iron; Lung Neoplasms; Male; Middle Aged; Neoplasms; Ovarian Neoplasms; Quality of Life; Recombinant Proteins; Reticulocyte Count

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

In an effort to obtain defined culture conditions for ex vivo expansion of hematopoietic stem and progenitor cells which avoid the supplementation of serum, we cultured human CD34(+) hematopoietic progenitor cells in a chemically defined, serum-free medium in the presence of hematopoietic growth factors (HGFs), stem cell factor (SCF), interleukin (IL)-1beta, IL-3, IL-6, and erythropoietin (EPO). A medium, SFM-1, was prepared according to a protocol previously optimized for semisolid progenitor cell assays containing Iscove's Modified Dulbecco's Medium (IMDM) plus cholesterol, bovine serum albumin, transferrin, nucleotides and nucleosides, insulin, and beta-mercaptoethanol. In static cultures seeded with CD34(+)-enriched progenitor cells isolated from human peripheral blood, a mean 76.6-fold expansion of total nucleated cells and a mean 4.6-fold expansion of colony-forming cells (CFC) was recorded after 14 days. Morphological analysis of the expanded cells revealed formation of myeloid, erythroid, and megakaryocytic cells. Flow cytometric analysis indicated that CD34(+) antigen expressing cells were maintained to a limited degree only, and cell populations expressing surface markers for myeloid (CD33, CD14, and CD15) and megakaryocytic (CD41a) lineages predominated. Within SFM-1, bovine serum albumin (BSA), cholesterin, and transferrin represented the most critical components needed for efficient total cell and CFC expansion. Addition of autologous patient plasma (APP) or fetal calf serum (FCS) to SFM-1 resulted in inferior cell amplification and CFC formation compared to controls in SFM-1, indicating that the components used in SFM-1 could replace exogenous serum. Four commercially available serum-free media resulted in either comparable or lower total cell and CFC yields as SFM-1. The transplantation potential of CD34(+) cells after culture in SFM-1 was assayed using limiting dilution analysis on preformed irradiated bone marrow stroma and revealed maintenance of long-term bone marrow culture initiating cell (LTCIC) levels during the culture period. These data indicate that HGF-supported multilineage ex vivo expansion of human CD34(+) hematopoietic progenitor cells is feasible using an IMDM-based culture medium which contains a restricted number of additives, resulting in analogous or improved yields of both primitive and differentiated cells compared to previously established protocols. We suggest that this culture protocol is of advantage when working

Topics: Animals; Antigens, CD; Antigens, CD34; Biomarkers; Bone Marrow Cells; Cattle; Cell Culture Techniques; Cell Division; Culture Media, Serum-Free; Erythropoietin; Granulocyte Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Interleukins; Neoplasms; Serum Albumin, Bovine; Stem Cell Factor; Stromal Cells

The transplantation of polymer encapsulated myoblasts genetically engineered to secrete erythropoietin (Epo) may obviate the need for repeated parenteral administration of recombinant Epo as a treatment for chronic renal failure, cancer or AIDS-associated anemia. To explore this possibility, the human and mouse Epo cDNAs under the control of the housekeeping mouse PGK-1 promoter were transfected into mouse C2C12 myoblasts, which can be terminally differentiated upon exposure to low serum-containing media. Pools releasing 150 IU human Epo per 10(6) cells per day and 390 IU mouse Epo per 10(6) cells per day were selected. Polyether-sulfone (PES) capsules loaded with approximately 200,000 transfected myoblasts from these pools were implanted on the dorsal flank of DBA/2J, C3H and C57BL/6 mice. With human Epo secreting capsules, only a transient increase in the hematocrit occurred in DBA/2J mice, whereas no significant response was detected in C3H or C57BL/6 mice. On the contrary, all mice implanted with capsules releasing mouse Epo increased their hematocrit over 85% as early as 7 days after implantation and sustained these levels for at least 80 days. All retrieved implants released Epo and contained well preserved myoblasts. Moreover most capsules were surrounded by a neovascularization. Mice transplanted with nonencapsulated C2C12 cells releasing mouse Epo showed only a transitory elevation of their hematocrit reflecting the poor engraftment of injected myoblasts. These results indicate that polymer encapsulation of genetically engineered myoblasts is a promising approach for the long-term delivery of bioactive molecules, allowing the resolution of the shortcomings of free myoblast transfer.

Topics: Acquired Immunodeficiency Syndrome; Analysis of Variance; Anemia; Animals; Antibodies, Monoclonal; Capsules; Cell Line; Erythropoietin; Female; Genetic Engineering; Genetic Therapy; Genetic Vectors; Hematocrit; Humans; Injections, Intramuscular; Kidney Failure, Chronic; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred DBA; Muscle, Skeletal; Neoplasms; Time Factors; Transfection

To study the impact of Procrit (epoetin alfa; Amgen Inc, Thousand Oaks, CA) on quality of life, transfusion requirements, and hemoglobin in anemic cancer patients receiving chemotherapy.. More than 500 community-based oncologists enrolled 2,342 patients with malignancies undergoing cytotoxic chemotherapy in an open-label study. Patients were treated with epoetin alfa 150 U/kg three times weekly, which could be doubled if the therapuetic response was judged inadequate. Total treatment was up to 4 months.. Of the 2,342 patients enrolled, data were available for 2,030 patients. Of the 2,030, 1,047 patients completed all 4 months of epoetin alfa therapy. Epoetin alfa was associated with significant increases in mean self-rated scores for energy level, activity level, and overall quality of life; these improvements correlated with the magnitude of the hemoglobin increase and were independent of tumor response. In addition, epoetin alfa was associated with a significant increase in mean hemoglobin and with a significant decrease in the proportion of patients requiring transfusions (baseline to final value, P < .001). Epoetin alfa was well tolerated.. Epoetin alfa is effective in improving the functional status and quality of life in anemic cancer patients receiving chemotherapy, as well as increasing hemoglobin level and decreasing transfusion requirements. Improvement in functional status can be attributed to an increase in hemoglobin level, demonstrating that quality of life in this group of patients can be improved by aggressively treating anemia. Further studies will be required to define the optimal doses and schedules for epoetin alfa.

Topics: Anemia; Blood Transfusion; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins; Renal Dialysis

Topics: Cell Hypoxia; DNA-Binding Proteins; Erythropoietin; Gene Expression Regulation; Homeostasis; Humans; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Neoplasms; Nuclear Proteins; Oxygen Consumption; Receptors, Aryl Hydrocarbon; Transcription Factors

The improvement of tumor control rates and improved survival times of radiotherapy patients result in an increasing importance of radiation side effects in normal tissues.. Possibilities for the modulation of normal tissue reaction by stimulation of tissue regeneration, or by interference with general pathogenetic pathways which are not specific for radiation damage, are illustrated by a number of examples.. Increasing knowledge about the pathogenesis of normal tissue radiation responses are expected to significantly improve the efficacy of prophylactic means and possibilities for conservative management of side effects of radiation therapy. Novel approaches may be developed if the so-called "humoral radiation pathology" is taken into consideration in addition to the cellular effects of radiation.

Topics: Erythropoietin; Growth Substances; Humans; Neoplasms; Radiation Injuries; Radiotherapy; Survival Rate

1) Does erythropoietin (EPO) reduce the need for transfusion of red blood cells in patients receiving chemotherapy for a nonhematologic cancer? 2) Does the administration of EPO improve the quality of life of these cancer patients?. To make recommendations regarding the use of EPO to reduce the need for transfusion of red blood cells in patients receiving chemotherapy for a nonhematologic cancer.. First transfusion requirement from the start of chemotherapy is the main outcome of interest. Quality of life and costs are also considered.. Evidence was selected and reviewed by 5 members of the Ontario Cancer Treatment Practice Guidelines Initiative (OCTPGI) and the Systemic Treatment Program Committee (STPC). Drafts of this document have been circulated to and reviewed by members of the STPC. The STPC comprises medical oncologists, pharmacists, supportive care personnel and administrators. No community representative participated in the development of this practice guideline.. Eleven randomized controlled trials (RCTs), most placebo-controlled, were available for review. A meta-analysis was performed with 8 trials that shared a clinically relevant outcome measure. Only 1 trial assessed quality of life.. The meta-analysis showed a relative risk for transfusion among EPO patients of 0.64 (95% confidence interval 0.53-0.78), which translates into a 36% relative reduction in the proportion of patients requiring transfusion (p = 0.00001). Reduction in transfusion requirements was similar across strata defined by methodological quality, EPO dose, hematologic status, tumour type at trial entry and chemotherapy regimen. In the 1 trial that assessed quality of life, EPO was associated with improved quality of life.. Hypertension has been noted rarely in EPO-treated cancer patients. The RCTs did not report adverse effects in EPO-treated patients compared with control patients during the follow-up period. Long-term adverse effects are unknown. EPO is more costly than transfusion, but formal cost-effectiveness studies are unavailable.. For patients receiving chemotherapy for nonhematologic cancer in whom symptoms of anemia are expected and in whom transfusion of red blood cells is not considered an acceptable treatment option, EPO can be recommended as a safe, effective treatment alternative. The evidence in support of using EPO is stronger for patients receiving platinum-based chemotherapy regimens that for those receiving non-platinum-based regimens. CLINICAL PRACTICE GUIDELINE DATE: Apr. 4, 1997.

Topics: Anemia; Antineoplastic Agents; Drug Costs; Erythrocyte Transfusion; Erythropoietin; Follow-Up Studies; Humans; Hypertension; Meta-Analysis as Topic; Neoplasms; Outcome Assessment, Health Care; Platinum Compounds; Quality of Life; Randomized Controlled Trials as Topic; Risk Factors

Topics: Anemia; Antineoplastic Agents; Cisplatin; Double-Blind Method; Erythrocyte Volume; Erythropoietin; Follow-Up Studies; Hemoglobins; Humans; Hypertension; Kidney; Neoplasms; Recombinant Proteins

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Blood Transfusion; Breast Neoplasms; Child; Child, Preschool; Combined Modality Therapy; Cost-Benefit Analysis; Epoetin Alfa; Erythropoietin; Female; Humans; Middle Aged; Neoplasms; Recombinant Proteins; Risk Assessment

Thrombopoietin, the ligand for the c-mpl receptor, promotes proliferation and maturation of megakaryocytes. An ELISA using a chimaeric receptor, mpl-IgG, for capture, and rabbit antibody to thrombopoietin for detection was developed for the quantitation of thrombopoietin in human serum or plasma. This ELISA preferentially detects full-length thrombopoietin compared to the bioactive N-terminal half of the molecule which has homology to erythropoietin. Thrombopoietin was not detected (< 0.16 ng/ml) in 88/89 healthy individuals. However, elevated thrombopoietin concentrations of up to 3 ng/ml were detected in 59/63 thrombocytopenic patients, including cancer patients following chemotherapy. In cancer patients receiving chemotherapy with (n = 12) or without (n = 6) peripheral blood progenitor cell transplantation, thrombopoietin concentrations varied inversely with platelet counts throughout the treatment period. In general, patients who received myeloablative chemotherapy on days -7 to -2 and peripheral blood progenitor cell transplantation on day 0 had high thrombopoietin levels (0.6-2.9 ng/ml) around day 5. Low platelet counts (< 20 x 10(9)/l) occurred between days 4 and 9. Patients who received high-dose chemotherapy on day 1 (equivalent to day -7 for transplantation patients) to day 6 without transplantation had high thrombopoietin concentrations (1.4-2.3 ng/ml) around day 13 and low platelet counts occurred between days 7 and 17.

Topics: Adult; Aged; Antineoplastic Agents; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Neoplasms; Platelet Count; Thrombocytopenia; Thrombopoietin

Topics: Anemia; Chronic Disease; Elective Surgical Procedures; Erythropoietin; Humans; Inflammation; Neoplasms; Preoperative Care; Recombinant Proteins

Topics: Acquired Immunodeficiency Syndrome; Anemia; Drug Resistance; Erythropoietin; Humans; Infections; Kidney Failure, Chronic; Neoplasms; Recombinant Proteins

The two sample analysis of covariance model is considered where the regression lines are found not to be parallel. There are two analyses often utilized in this case. One is to obtain a standard confidence interval for the covariate value where the two lines intersect, and the other is to find a simultaneous confidence region for the difference between the regression lines. The asymptotic robustness to heteroscedasticity of the regressions' errors of the coverage probability of each of these two confidence procedures is considered. When the sample sizes are approximately equal, and the covariate means and the covariate variances are similar between the samples, the unequal regression variances are shown to have little effect on the asymptotic coverage probabilities of these two confidence procedures. Discussions concerning the effects of unequal sample sizes and inequitably distributed covariate values are also presented. These results are illustrated in application to a clinical trial of recombinant human erythropoetin versus placebo to treat patients with anemia secondary to advanced cancer, who were not receiving chemotherapy.

Topics: Analysis of Variance; Anemia; Controlled Clinical Trials as Topic; Erythropoietin; Humans; Mathematics; Models, Statistical; Neoplasms; Recombinant Proteins; Regression Analysis

Adoptive immunotherapy with tumor-infiltrating lymphocytes (TILs) causes regression of some human tumors. However, the sustained proliferation and antitumor activity of TILs requires the coadministration of potentially toxic amounts of interleukin-2 (IL-2). In an effort to overcome the requirement by T cells for IL-2, we have introduced alternative growth factor receptors that use the relatively nontoxic cytokine erythropoietin (Epo) as a ligand. In our model system, the coexpression of chimeric receptors consisting of the extracellular portion of the Epo receptor (EpoR) and the intracellular portions of the IL-2 receptor subunits, beta and gamma, conferred Epo responsiveness on a T-cell line. By contrast, cells expressing the wild-type EpoR did not proliferate in response to Epo. This suggested that Epo binding caused the activation of an IL-2 signal pathway mediated by the chimeric receptors. This approach can be used to minimize toxicity and potentially improve cancer immunotherapy with TILs.

Topics: Animals; Base Sequence; Cell Line; Erythropoietin; Genetic Vectors; Humans; Immunotherapy, Adoptive; Interleukin-2; Lymphocytes, Tumor-Infiltrating; Mice; Molecular Sequence Data; Neoplasms; Receptors, Erythropoietin; Receptors, Interleukin-2; Recombinant Fusion Proteins; Retroviridae; Signal Transduction; T-Lymphocytes; Transfection

Patients with cancer often develop significant anemia, which traditionally has been successfully managed by transfusion. Although substantially safer than in the past, transfusions continue to carry a variety of risks. The recent licensing of erythropoietin now provides a second treatment option, which indicates a need to reassess the use of transfusion to manage anemia in these patients.. A 12-month retrospective chart review of all patients receiving outpatient transfusions at a large institution was used to identify patients with solid tumors (including lymphoma) requiring transfusions for any cause. Transfusions were considered as aberrations if they necessitated unusual laboratory monitoring or resulted in clinical evidence of a transfusion reaction. Patient charges proximately related to the transfusion were calculated.. A total of 219 patients requiring transfusions were identified, with 483 transfusion episodes and the use of 812 units of red cells to manage anemia (mean, 3.71 units/patient). A total of 100 aberrations were recorded. Twenty-two (10%) of 219 patients had a positive antibody screen that required further work-up; transfusion reactions occurred in 19 patients (8.7%).. Careful assessment by hematologists and oncologists of the risk:benefit ratio of erythropoietin and transfusion in patients with cancer is urged.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Blood Transfusion; Child; Child, Preschool; Cost-Benefit Analysis; Erythropoietin; Humans; Middle Aged; Neoplasms; Retrospective Studies; Risk Factors; Transfusion Reaction

Topics: Anemia; Erythropoietin; Hemoglobins; Humans; Neoplasms; Recombinant Proteins; Reticulocyte Count

Erythropoietin (EPO) levels in plasma from 124 clinically anemic dogs were determined by in vivo bioassay. In 81 anemic dogs with normal renal function, the concentration of plasma EPO showed a close correlation with the hemoglobin concentration. The plasma EPO level was obviously decreased in 43 anemic dogs with renal failure. Of these dogs with renal failure, 17 showed no detectable plasma EPO and resulted in the death of these dogs. In the remaining 26 dogs having detectable plasma EPO, the plasma concentration rate of EPO related to blood urea nitrogen and serum creatinine values.

Topics: Anemia; Animals; Blood Urea Nitrogen; Creatinine; Dog Diseases; Dogs; Erythropoietin; Female; Hemoglobins; Male; Neoplasms; Regression Analysis; Renal Insufficiency

Umbilical cord blood (UCB) and mobilized peripheral blood (MPB) provide an alternate source to bone marrow for transplantation. Expansion in vitro of stem/progenitor cell populations from these sources may provide adult-sized grafts otherwise not attainable because of the limited cell numbers available in the case of UCB or because of numerous rounds of apheresis required for sufficient MPB cells. We asked whether continuous perfusion culture could be employed in ex vivo expansion to produce clinically relevant numbers of stem/progenitor cells from these sources. To evaluate MPB, 1-10 million leukocytes, from patients who had received either granulocyte colony-stimulating factor (G-CSF) or cyclophosphamide and granulocyte-macrophage colony-stimulating factor (GM-CSF), were inoculated into bioreactors, with or without irradiated, allogeneic stroma. The growth factor combination in the perfusion medium consisted of interleukin-3 (IL-3), stem cell factor (SCF), GM-CSF and erythropoietin (Epo). Under the best conditions tested, total cell numbers, granulocyte-macrophage colony-forming units (CFU-GM), and long-term culture-initiating cell (LTC-IC) populations were expanded by about 50-, 80-, and 20-fold, respectively, over 14 days. At low cell inocula (1 million), the presence of stroma enhanced the expansion of total cells and CFU-GM but not of LTC-IC. When SCF was not included in the medium, both total cells and CFU-GM expanded to a much lesser extent, but again the expansion of LTC-IC was not affected. At the higher cell inoculum (10 million), expansions of total cells and CFU-GM were equivalent with or without stroma. To evaluate UCB, cells were placed into bioreactors with or without irradiated, allogeneic stroma, and the bioreactors were perfused with medium containing the four standard growth factors. After 6-14 days, in several independent experiments, 20-24 million cells were harvested from bioreactors perfused with SCF-containing medium, irrespective of the presence or absence of preformed stroma. Similarly, in reactors perfused with SCF-containing medium (with or without stroma), an average 40- to 60-fold expansion of CFU-GM was obtained, yielding an average of 1.5-1.8 x 10(5) CFU-GM per reactor. Harvested cells were thus up to 40-fold enriched in CFU-GM in comparison to the inoculum. In the absence of SCF, cell expansions averaged 1.5- to 2-fold, and CFU-GM were expanded only 10- to 14-fold by day 14. As before, the presence of preformed stroma did

Topics: Adult; Blood Cells; Bone Marrow; Cell Count; Cell Differentiation; Connective Tissue; Culture Techniques; Drug Synergism; Erythropoietin; Fetal Blood; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoiesis; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cells; Humans; Infant, Newborn; Interleukin-3; Neoplasms; Perfusion; Stem Cell Factor

Anemia is common in cancer patients and may require treatment for symptomatic palliation. Transfusion has been the mainstay of therapy, but is not without risk. Because erythropoietin levels in cancer-related anemia are inadequate for the degree of anemia, recombinant human erythropoietin has been studied to treat the anemia. Results from these studies are encouraging.

Topics: Anemia; Blood Transfusion; Clinical Trials as Topic; Combined Modality Therapy; Cost-Benefit Analysis; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Anemia is common in patients with cancer and is often exacerbated by myelosuppressive chemotherapy. If severe enough, the anemia may require red blood cell transfusion for symptomatic palliation. However, blood transfusion will never be completely safe. Inconvenience and acute transfusion reactions are a problem and there is still a small risk of hepatitis. In selected patients with cancer-related anemia, recombinant human erythropoietin is another option to consider for the symptomatic patient.

Topics: Anemia; Blood Transfusion; Clinical Trials as Topic; Costs and Cost Analysis; Erythropoietin; Humans; Neoplasms; Recombinant Proteins; United States

Topics: Anemia; Blood Transfusion; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Topics: Anemia; Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Hypoxia; Cytokines; Erythropoietin; Humans; Interleukin-1; Neoplasms; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

Topics: Anemia; Biomarkers; Biopterins; Erythropoietin; Ferritins; Hemoglobins; HIV Infections; Humans; Interferon-gamma; Leukemia; Neoplasms; Neopterin; Reference Values

Topics: Acquired Immunodeficiency Syndrome; Anemia; Arthritis, Rheumatoid; Autoimmune Diseases; Blood Donors; Erythropoietin; Hematologic Diseases; Humans; Kidney Failure, Chronic; Neoplasms; Recombinant Proteins

To provide sufficient numbers of peripheral blood progenitor cells (PBPCs) for repetitive use after high-dose chemotherapy, we investigated the ability of hematopoietic growth factor combinations to expand the number of clonogenic PBPCs ex vivo. Chemotherapy plus granulocyte colony-stimulating factor (G-CSF) mobilized CD34+ cells from 18 patients with metastatic solid tumors or refractory lymphomas were cultured for up to 28 days in a liquid culture system. The effects of interleukin-1 beta (IL-1), IL-3, IL-6, granulocyte-macrophage-CSF (GM-CSF), G-CSF, macrophage-CSF (M-CSF), stem cell factor (SCF), erythropoietin (EPO), leukemia inhibitory factor (LIF), and interferon-gamma, as well as 36 combinations of these factors were tested. A combination of five hematopoietic growth factors, including SCF, EPO, IL-1, IL-3, and IL-6, was identified as the optimal combination of growth factors for both the expansion of total nucleated cells as well as the expansion of clonogenic progenitor cells. Proliferation peaked at days 12 to 14, with a median 190-fold increase (range, 46- to 930-fold) of total clonogenic progenitor cells. Expanded progenitor cells generated myeloid (colony-forming unit-granulocyte-macrophage), erythroid (burst-forming unit-erythroid), as well as multilineage (colony-forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte) colony-forming units. The number of multilineage colonies increased 250-fold (range, 33- to 589-fold) as compared with pre-expansion values. Moreover, the absolute number of early hematopoietic progenitor cells (CD34+/HLA-DR-; CD34+/CD38-), as well as the number of 4-HC-resistant progenitors within expanded cells increased significantly. Interferon-gamma was shown to synergize with the 5-factor combination, whereas the addition of GM-CSF significantly decreased the number of total clonogenic progenitor cells. Large-scale expansion of PB CD34+ cells (starting cell number, 1.5 x 10(6) CD34+ cells) in autologous plasma supplemented with the same 5-factor combination resulted in an equivalent expansion of progenitor cells as compared with the microculture system. In summary, our data indicate that chemotherapy plus G-CSF-mobilized PBPCs from cancer patients can be effectively expanded ex vivo. Moreover, our data suggest the feasibility of large-scale expansion of PBPCs, starting from small numbers of PB CD34+ cells. The number of cells expanded ex vivo might be sufficient for repetitive use after high-dose chemotherapy an

Topics: Antigens, CD; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cell Division; Cells, Cultured; Colony-Forming Units Assay; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Growth Inhibitors; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Ifosfamide; In Vitro Techniques; Interferon-gamma; Interleukin-1; Interleukin-3; Interleukin-6; Interleukins; Kinetics; Leukemia Inhibitory Factor; Lymphokines; Lymphoma; Macrophage Colony-Stimulating Factor; Neoplasms; Recombinant Proteins; Stem Cell Factor; Vincristine

Topics: Anemia; Anemia, Refractory; Blood Preservation; Blood Transfusion, Autologous; Erythropoiesis; Erythropoietin; Hematologic Diseases; Humans; Inflammation; Neoplasms; Receptors, Erythropoietin; Recombinant Proteins; Renal Dialysis

Topics: Adult; Drug Utilization; Erythropoietin; Humans; Neoplasms; Orthopedics

To analyze the relationship between serum erythropoietin levels and hemoglobin levels in elderly patients with anemia of chronic disorders related to cancer or acute infection when compared with anemic patients with iron deficiency.. Prospective survey with comparison groups.. Tertiary care center.. An elderly group aged 70 and above (mean 84, range 70-96) was divided into subgroups of 45 with anemia of chronic disorders (23 with cancer and 22 with acute infection), 24 with iron-deficiency anemia, and 27 with no anemia. Thirty non-anemic younger adults were also studied.. Serum erythropoietin (radioimmunoassay), complete blood count, serum iron, B12, folate and ferritin, liver and kidney function tests, blood gas analyses, and bacteriological and radiological tests.. The serum erythropoietin levels were significantly lower in the elderly non-anemic hospitalized group than in the healthy younger group. A significant negative relationship between the log serum erythropoietin and hemoglobin levels was found in patients with iron deficiency, but not in the other groups. For any given hemoglobin level, the response of erythropoietin was significantly higher in anemic patients with iron deficiency when compared with the neoplastic and infectious group.. Erythropoietin response to anemia is blunted in elderly patients with anemia of chronic disorders related to cancer or acute infection. Erythropoietin level is lower in non-anemic elderly inpatients than in healthy younger persons.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anemia; Anemia, Hypochromic; Case-Control Studies; Chronic Disease; Erythropoietin; Female; Hemoglobins; Hospitalization; Humans; Infections; Male; Neoplasms; Prospective Studies

Topics: Adult; Aged; Aged, 80 and over; Anemia; Blood Transfusion; Chronic Disease; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Neoplasms; Pilot Projects; Quality of Life; Recombinant Proteins

Topics: Cisplatin; Erythropoietin; Ferritins; Humans; Iron; Neoplasms

Topics: Erythropoietin; Humans; In Vitro Techniques; Neoplasms; Neoplastic Stem Cells; Recombinant Proteins; Tumor Cells, Cultured

Topics: Acquired Immunodeficiency Syndrome; Arthritis, Rheumatoid; Erythropoietin; Forecasting; Humans; Neoplasms; Postoperative Care

Topics: Anemia; Blood Transfusion; Erythropoietin; Hematocrit; Humans; Neoplasms

Topics: Blood Donors; Blood Transfusion, Autologous; Contraindications; Erythropoietin; Health Services Misuse; Humans; Neoplasm Recurrence, Local; Neoplasms; Recombinant Proteins; Risk Factors; Transfusion Reaction

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Erythropoietin; Humans; Neoplasms; Recombinant Proteins

Mild to moderate anemia associated with malignant disease can contribute to the overall morbidity in patients with cancer. Because this anemia has been linked to a blunted erythropoietin response, recombinant human erythropoietin (r-HuEPO) was assessed as a means to correct it and provide some degree of palliation. Three different patient populations were studied: one population not administered chemotherapy, a second population administered chemotherapy that did not include cisplatin, and a third population administered chemotherapy that included cisplatin. In all patient populations, r-HuEPO increased hematocrit values compare with placebo. In the two chemotherapy-treated populations, r-HuEPO decreased blood transfusion requirements after the first month of therapy. Patient-rated energy levels, ability to engage in daily activity, and overall quality of life improved in patients who responded to r-HuEPO therapy with an increase in hematocrit values of 6 percentage points or more. Thus, it appears that r-HuEPO may be a useful adjunct for palliation and treatment of anemia in patients with cancer.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Cisplatin; Erythropoietin; Female; Hematocrit; Humans; Male; Middle Aged; Neoplasms; Quality of Life; Recombinant Proteins; Treatment Outcome

Serum immunoerythropoietin (SIE) levels were studied of 25 randomly chosen cancer patients undergoing cisplatin-based chemotherapy and ten head and neck cancer patients who were studied prospectively before and during cisplatin-based therapy. The SIE levels were determined by standard radioimmunoassay, and the results were interpreted relative to erythropoietin levels and hematocrits of 17 aplastic or nutritionally anemic patients who were believed to have a normal erythropoietin response. Of the 25 randomly chosen patients, SIE levels were inappropriately low in four patients. In this population, there was a greater likelihood of erythropoietin deficiency in the patients with a hematocrit less than 30% compared with those with higher values (P less than 0.001), although there was no correlation between SIE level and the amount of cisplatin these patients received or their degree of renal impairment. Of the ten head and neck cancer patients, five were found to have inappropriately low SIE levels before therapy, and two additional patients had a decrease of SIE levels during therapy, in one patient to an abnormally low level. The anemia associated with malignancy was concluded to be in part associated with a relative erythropoietin deficiency, and in certain individuals, cisplatin therapy may contribute to that deficiency.

Topics: Adult; Aged; Anemia; Carcinoma, Non-Small-Cell Lung; Cisplatin; Cohort Studies; Erythropoietin; Female; Head and Neck Neoplasms; Hematocrit; Humans; Lung Neoplasms; Lymphoma; Male; Middle Aged; Neoplasms; Ovarian Neoplasms; Prospective Studies

Immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells results in significant tumor regression in patients with advanced cancer. We have investigated the kinetics of circulating erythroid (BFU-E) and granulocytic-macrophage (CFU-GM) progenitors after IL-2 therapy in 11 cancer patients, mainly affected by metastatic melanoma and renal cell carcinoma. Administration of IL-2 from day 1 through day 5 constantly induced a dramatic decrease of the number of circulating BFU-E and CFU-GM, which then showed a striking rebound (up to values fourfold and sevenfold higher, respectively, than the pretherapy levels) on discontinuation of IL-2, ie, from day 5 through day 10. A similar kinetic pattern was observed during and after the second cycle of IL-2 administration. 3[H]-thymidine killing experiments showed that the cycling activity of the progenitors was virtually unmodified in the rebound phases. To explore the mechanism(s) underlying this kinetic pattern, we have analyzed the plasma concentration of several hematopoietic growth factors, including IL-1 beta, IL-3, IL-4, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, and erythropoietin (Ep). No modifications in the levels of IL-3, GM-CSF, or IL-1 beta were observed, whereas a pronounced increase of IL-6 and G-CSF concentration was monitored, starting at day 3 and peaking at day 5 of treatment (a parallel, but modest, increase of Ep level was also observed). The elevation of IL-6 and G-CSF concentration is directly correlated with and may, at least in part, underlie the subsequent rebound of circulating hematopoietic progenitors. Furthermore, the increase in IL-4 level observed at day 10 of therapy may mediate the eosinophilia gradually starting at this stage of treatment.

Topics: Adult; Aged; Carcinoma, Renal Cell; Cell Count; Erythroid Precursor Cells; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Granulocytes; Growth Substances; Hematopoietic Stem Cells; Humans; Immunotherapy, Adoptive; Interleukin-2; Interleukin-6; Kidney Neoplasms; Kinetics; Macrophages; Male; Melanoma; Middle Aged; Neoplasms

Topics: Anemia; Blood Banks; Blood Transfusion, Autologous; Erythrocyte Transfusion; Erythropoietin; Hemoglobins; Humans; Neoplasms; Preoperative Care; Recombinant Proteins