epoetin-alfa and Neoplasms

Biosimilars are biologic drug products that are highly similar to reference products in analytic features, pharmacokinetics and pharmacodynamics, immunogenicity, safety, and efficacy. Biosimilar epoetin received Food and Drug Administration (FDA) approval in 2018. The manufacturer received an FDA nonapproval letter in 2017, despite receiving a favorable review by FDA's Oncologic Drugs Advisory Committee (ODAC) and an FDA nonapproval letter in 2015 for an earlier formulation. We discuss the 2018 FDA approval, the 2017 FDA ODAC Committee review, and the FDA complete response letters in 2015 and 2017; review concepts of litigation, naming, labeling, substitution, interchangeability, and pharmacovigilance; review European and U.S. oncology experiences with biosimilar epoetin; and review the safety of erythropoiesis-stimulating agents. In 2020, policy statements from AETNA, United Health Care, and Humana indicated that new epoetin oncology starts must be for biosimilar epoetin unless medical need for other epoetins is documented. Empirical studies report that as of 2012, reference epoetin use decreased from 40%-60% of all patients with cancer with chemotherapy-induced anemia to <5% of such patients because of safety concerns. Between 2018 and 2020, biosimilar epoetin use varied, increasing to 81% among one private insurer's patients covered by Medicare whose cancer care is administered with Oncology Analytics and to 41% with the same private insurer's patients with cancer covered by commercial health insurance and administered by the private insurer, to 0% in several Veterans Administration Hospitals, increasing to 100% in one large county hospital in California, and with yet-to-be-reported data from most oncology settings. We conclude that biosimilar epoetin appears to have overcome some barriers since 2015, although current uptake in the U.S. is variable. Pricing and safety considerations for all erythropoiesis-stimulating agents are primary determinants of biosimilar epoetin oncology uptake. IMPLICATIONS FOR PRACTICE: Few oncologists understand substitution and interchangeability of biosimilars with reference drugs. Epoetin biosimilar is new to the market, and physician and patient understanding is limited. The development of epoetin biosimilar is not familiar to oncologists.

Topics: Aged; Anemia; Antineoplastic Agents; Biosimilar Pharmaceuticals; Epoetin Alfa; Humans; Medicare; Neoplasms; United States

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

Biologics are widely used to manage the side effects of cancer treatment (e.g., epoetin alfa is used to treat chemotherapy-induced anemia [CIA] and granulocyte colony-stimulating factors [G-CSFs] are used to treat chemotherapy-induced neutropenia [CIN]). As several patents for biologics used in cancer treatment have expired, a number of companies have developed supportive care biosimilars (e.g., epoetin alfa biosimilar, filgrastim biosimilar, pegfilgrastim biosimilar).. The objective of this study was to synthesize current evidence on the efficacy and safety of supportive care biosimilars compared with their reference biologics in oncology.. We searched PubMed, Embase, the Cochrane library, ClinicalTrials.gov, ISI Web of Science and several Chinese databases from their inception dates to December 31, 2018 for randomized controlled trials (RCTs) or comparative observational studies that compared the efficacy and safety of supportive care biosimilars and their reference biologics in oncology. We pooled results separately for RCTs and observational studies, as such studies involve different patient populations and are designed differently. We pooled binary outcomes using risk ratios (RR) with confidence intervals (CIs) and continuous outcomes using weighted mean differences (WMD) with 95% CIs, then conducted subgroup and sensitivity analyses. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the quality of evidence.. We identified 28 studies that compared biosimilars of G-CSF or epoetin alfa: one RCT and five cohort studies (total N = 2816) of epoetin alfa biosimilars, and 13 RCTs and 9 cohort studies (total N = 23,043) of G-CSF biosimilars [corrected]. Despite involving different populations, RCTs and observational studies comparing biosimilars and reference biologics indicated similar efficacy and safety results. Overall, there was no statistically significant difference in any efficacy or safety outcomes between any biosimilars and their corresponding original biologics (all p > 0.05). The quality of GRADE evidence of efficacy and safety outcomes was moderate or low. Findings were robust for all prespecified subgroup and sensitivity analyses.. Existing evidence suggests highly comparable efficacy and safety profiles for supportive care biosimilars and their reference biologics in oncology.

Topics: Anemia; Antineoplastic Agents; Biosimilar Pharmaceuticals; Chemotherapy-Induced Febrile Neutropenia; Epoetin Alfa; Filgrastim; Hematologic Agents; Humans; Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome

While prescribing biosimilars to patients naive to a biologic treatment is a well-accepted practice, switching clinically stable patients from an originator to a biosimilar is an issue for clinicians. Well-designed clinical trials and real-world data which study the consequences of switching from an originator biologic treatment to its biosimilar alternative are limited, especially for monoclonal antibodies. Areas covered: A systematic literature review was conducted on PubMed to identify evidence of the consequences of switching from original biologics to biosimilars. References of included papers were also scrutinized. After a title-, abstract- and full text screening, out of the 153 original hits and 77 additional ones from screening the references, 58 papers (12 empirical papers, 5 systematic reviews and 41 non-empirical papers) were included. Expert opinion: Preventing patients on biologic medicines from switching to biosimilars due to anticipated risks seems to be disproportional compared to the expected cost savings and/or improved patient access. Indeed, it is the opinion of the authors that the concern of switching to biosimilars is overhyped.

Topics: Anemia; Biosimilar Pharmaceuticals; Databases, Factual; Epoetin Alfa; Health Care Costs; Humans; Inflammatory Bowel Diseases; Kidney Failure, Chronic; Neoplasms; Red-Cell Aplasia, Pure; Rheumatic Diseases; Risk

Biosimilar drugs are biologic drugs clinically similar to the reference products. They correspond to a generic approach applied to biologic agents. Biosimilars are aimed to provide cheaper drugs by enhancing the concurrency. The approval of biosimilars is abbreviated when compared to that of the reference biologics but includes clinical trials (distinguishing them from the generics). Current available biosimilars in oncology are filgrastim and epoietin alpha. In the next future, will be launched rituximab and trastuzumab. In France, the development of biosimilars is faced with many hurdles that necessitates a better information of physicians and a greater price discount in the out-patient setting. More globally, harmonisation of recommendations particularly concerning extrapolation of indications and nomenclature are needed for a better acceptance.

Topics: Biosimilar Pharmaceuticals; Epoetin Alfa; Filgrastim; Forecasting; France; Humans; Neoplasms; Rituximab; Trastuzumab

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 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 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

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

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 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

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 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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; 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

Erythropoiesis-stimulating agents (ESAs) epoetin alfa (EA) and darbepoetin alfa (DA) increase hemoglobin (Hb) levels and reduce red blood cell (RBC) transfusion requirements in patients with cancer chemotherapy-associated anemia (CAA). Extended-interval ESA dosing (administration less than once weekly) is common with DA, but previous studies suggested that EA might also be administered less often than weekly. In this multicenter prospective trial, 239 CAA patients with Hb <10.5 g/dL were randomized to receive EA 40,000 U subcutaneously once weekly ("40K" arm), EA 80,000 U every 3 weeks ("80K"), EA 120,000 U every 3 weeks ("120K" arm), or DA 500 mcg every 3 weeks ("DA"), for 15 weeks. The primary endpoint was the proportion of patients achieving Hb ≥ 11.5 g/dL or increment of Hb > 2.0 g/dL from baseline without transfusion. Secondary endpoints included transfusion requirements, adverse events (AEs), and patient-reported outcomes (PROs). There were no significant differences between treatment arms in the proportion of patients achieving Hb response (68.9% for 40K, 61.7% for 80K, 65.5% for 120K, and 66.7% for DA; P > 0.41 for all comparisons) or requiring RBC transfusion, but the median Hb increment from baseline was higher in the 40K and DA arms compared to the two extended dosing EA arms, and Hb response was achieved soonest in the weekly EA arm. There were no differences in PROs or AEs. The FDA-approved schedules tested-weekly EA 40,000 U, and every 3 week DA 500 mcg-are reasonable standards for CAA therapy.

Topics: Aged; Aged, 80 and over; Anemia; Darbepoetin alfa; Epoetin Alfa; Female; Hematinics; Hemoglobins; Humans; Male; Neoplasms

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

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 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The aim of the study was to evaluate in real-life conditions the effectiveness and safety of a biosimilar of epoetin alfa (Retacrit®) in chemotherapy-induced anemia and the impact of iron supplementation.. This was a longitudinal, observational, prospective study of 12-16 weeks conducted in 195 French centers. The primary endpoint was the achievement of target Hb (with an increase of Hb ≥1 g/dL) or an increase of Hb ≥2 g/dL, in the absence of transfusion in the previous 3 weeks.. 2,076 patients (women, 50.6%; mean age, 67.0 years) with malignant diseases (solid tumors, 79.8%; lymphomas, 12.7%; multiple myeloma, 6.6%) were analyzed. A total of 655 patients received oral iron (40.5%), intravenous iron (58.9%), or both (0.6%). At inclusion, 10.0% and 18.2% of patients without and with iron supplementation had serum ferritin <100 μg/L, respectively. Transferrin saturation (TSAT) ≤20% was more frequent in patients with supplementation (76.6%) than without supplementation (33.9%). The mean weekly doses of epoetin alfa biosimilar and planned duration of treatment were comparable regardless of iron supplementation. The primary endpoint was achieved in 70.5% and 70.2% of patients without and with iron supplementation, respectively. Three (0.1%) serious thromboembolic events related to treatment with epoetin alfa biosimilar were reported.. Epoetin alfa biosimilar was effective and well tolerated for treating chemotherapy-induced anemia. Patients in subgroup with iron supplementation had lower TSAT at inclusion compared to subgroup without supplementation. Comparable mean Hb levels were achieved in both subgroups. The rate of patients with iron supplementation through the intravenous route was however insufficient.

Topics: Aged; Anemia; Antineoplastic Agents; Biosimilar Pharmaceuticals; Dietary Supplements; Epoetin Alfa; Female; Ferritins; Hematinics; Humans; Iron; Neoplasms; Prospective Studies; Recombinant Proteins; Transferrins

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

Since the approval and availability of the first biosimilar in 2015 in the United States (US), evidence regarding the post-marketing safety of cancer supportive care biosimilars remains limited.. The aim was to explore the adverse event (AE) reporting patterns and detect disproportionate reporting signals for cancer supportive care biosimilars in the US compared to their originator biologics.. The US Food and Drug Administration Adverse Event Reporting System database (January 1, 2004-March 31, 2020) was used to identify AE reports for filgrastim, pegfilgrastim, and epoetin alpha by type of product (originator biologics vs. biosimilars) and report characteristics. Plots of AE reports against years were used to reveal the reporting patterns. Disproportionality analyses using reporting odds ratios (RORs) were conducted to detect differences in serious and specific AEs between studied drugs and all other drugs. Breslow-Day tests were used to determine homogeneity between the originator biologic-biosimilar pair RORs for the same AE.. Total numbers of AEs for all studied biosimilars increased after marketing. More AE reports were from female patients for all of the studied drugs. More AEs for originator biologics and filgrastim biosimilar were reported by health professionals, while the highest proportion of reports came from consumers for pegfilgrastim and epoetin alpha biosimilars (29% and 44.1%, respectively). Signals of disproportionate reporting in serious AEs were detected for a pegfilgrastim biosimilar (Fulphila. Our findings support the similarity in the signals of disproportionate reporting between cancer supportive care originator biologics and biosimilars, except for Fulphila

Topics: Biosimilar Pharmaceuticals; Databases, Factual; Epoetin Alfa; Female; Humans; Neoplasms; United States; United States Food and Drug Administration

Switching between different erythropoiesis-stimulating agents (ESAs) during the first year of therapy is frequent (15-20%), much more so toward reference products than biosimilars. The objectives of this study were to investigate the frequency and identify the potential predictors of switching between biosimilar and originator ESAs during the first year of treatment in patients with chronic kidney disease (CKD), or chemotherapy-related anemia from six large Italian geographic areas in the years 2009-2015.. A retrospective cohort study was conducted using six Italian regional claims databases (≥ 13 million inhabitants) during 2009-2015. Among incident epoetin users, the frequency of single, multiple, and backward switch during the first year of treatment was evaluated. Using frailty Cox models, potential predictors of first switch were identified. All analyses were stratified by the main indications for use.. Among 102,240 incident epoetin users, 15,853 (15.5%) switched to another epoetin during the first year of therapy; only 18% of these switched to biosimilars. Single switch was more common (62.2% of the switchers) than multiple (23.5%) or backward switch (14.3%). In cancer, the cumulative number of transfusions and iron preparations dispensed, as well as hyperparathyroidism, were predictors of switching. In CKD, the cumulative number of transfusions, number of vitamin A/D preparations dispensed, and CKD severity increased the probability of switching.. Switching between ESAs was frequent in both CKD and cancer patients. The number of cumulative transfusions and severity of disease seemed to affect the switch.

Topics: Aged; Anemia; Biosimilar Pharmaceuticals; Cohort Studies; Databases, Factual; Epoetin Alfa; Erythropoiesis; Female; Hematinics; Humans; Italy; Male; Neoplasms; Proportional Hazards Models; Renal Insufficiency, Chronic; Retrospective Studies

To evaluate the benefit/risk profile of epoetin α biosimilar with the erythropoiesis-stimulating agents (ESAs) originators when administered to naïve patients from clinical practice.. Population-based observational cohort study.. All residents in the Lazio Region, Italy, with chronic kidney disease (CKD) or cancer retrieved from the Electronic Therapeutic Plan (ETP) Register for ESA between 2012 and 2014.. Overall, 13 470 incident ESA users were available for the analysis, 8161 in the CKD and 5309 in the oncology setting, respectively.. ESAs identified through the ATC B03XA were divided into 3 groups: (1) biosimilars; (2) epoetin α originator and (3) other originators. Patients were exposed to ESAs from the date of activation of the ETP, until the end of a 6-month follow-up period.. Effectiveness (all-cause mortality and blood transfusion) and safety (major cardiovascular events, blood dyscrasia). A composite outcome including all-cause mortality, blood transfusion and major cardiovascular events was predefined. HRs of any outcome were estimated through Cox regression.. We found no differences between patients on biosimilars or all originators with regard to the risk estimates of all-cause mortality, blood transfusion, major cardiovascular events and blood dyscrasia in the CKD setting. The composite outcome confirmed these results (biosimilars vs epoetin α originators: adjusted HR=1.02, 95% CI 0.78 to 1.33; biosimilars vs other originators: adjusted HR=1.09, 95% CI 0.85 to 1.41). Comparable risk estimates were observed between biosimilars and all originators in the oncology setting.. In both settings, our findings are suggestive of no difference between biosimilars and originators on relevant effectiveness and safety outcomes. This study may contribute to settling future drug policy for the health services and provides reassurance on the approval pathway for biosimilars. The oncology setting merits further research, taking into account tumour types, tumour stage and anticancer chemotherapy administered.

Topics: Anemia; Biosimilar Pharmaceuticals; Blood Transfusion; Cardiovascular Diseases; Cause of Death; Epoetin Alfa; Erythropoiesis; Female; Hematinics; Humans; Italy; Male; Neoplasms; Proportional Hazards Models; Renal Insufficiency, Chronic; Risk Assessment; Treatment Outcome

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

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

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 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

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

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

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

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

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

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

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

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

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: 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

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

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

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

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

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

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

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

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

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; Clinical Trials as Topic; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Safety; Survival Analysis

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

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; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

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

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

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Hemoglobins; Humans; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

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

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

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

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

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

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

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

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

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins

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

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

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 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; Animals; Cell Hypoxia; Clinical Trials as Topic; Disease Models, Animal; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Recombinant Proteins

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

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

Topics: Anemia; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Practice Guidelines as Topic; Recombinant Proteins

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; 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

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

Topics: Anemia; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins; Research Design

(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

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: 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

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: 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: Anemia; Antineoplastic Agents; Child; Child, Preschool; Epoetin Alfa; Erythropoietin; Humans; Infant; Infant, Newborn; Infant, Premature; Iron; Kidney Failure, Chronic; Neoplasms; Radiotherapy; Recombinant Proteins

Topics: Anemia; Antineoplastic Agents; Cost-Benefit Analysis; Epoetin Alfa; Erythropoietin; Humans; 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

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

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: 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

Topics: Adenocarcinoma; Animals; Blood; Carcinoma; Carcinoma, Hepatocellular; Epoetin Alfa; Erythropoietin; Growth Substances; Humans; Iron; Iron Isotopes; Liver Extracts; Liver Neoplasms; Liver Neoplasms, Experimental; Lymphoma; Neoplasms; Neoplasms, Experimental; Radiometry; Rats

Topics: Adenocarcinoma; Blood Cell Count; Carcinoma, Renal Cell; Epoetin Alfa; Erythropoietin; Geriatrics; Humans; Kidney Neoplasms; Lung Neoplasms; Mercaptopurine; Neoplasm Metastasis; Neoplasms; Neoplasms, Second Primary; Nephrectomy

Topics: Epoetin Alfa; Erythropoietin; Gout; Humans; Kidney Diseases; Liver Diseases; Neoplasms; Polycythemia Vera; Thyroid Diseases

Topics: Aged; Epoetin Alfa; Erythropoietin; Humans; Neoplasms; Polycythemia; Polycythemia Vera