Epoetin alfa and darbepoetin alfa for the treatment of chemotherapy-related anemia in cancer patients in Sweden: Comparative analysis of drug utilization, costs, and hematologic response

A retrospective chart review was performed at 3 Swedish hospitals to evaluate the utilization, outcomes, and cost of using epoetin alfa or darbepoetin alfa to treat cancer patients with chemotherapy-related anemia. Data on dosage, duration of treatment, hematologic response, red blood cell transfusions, and healthcare resource consumption were collected and analyzed at various time points following the initiation of drug therapy. A significantly faster hematologic response and increase in hemoglobin were observed in patients treated with epoetin alfa. Dosages used in clinical practice appeared to be lower than those recommended by Swedish treatment guidelines. There were no significant differences in resource utilization or healthcare costs between the 2 treatment groups. By day 112, the mean treatment cost per patient, in Swedish kronors (SEK), was SEK74,701 (~US$9800 or E8300) with epoetin alfa and SEK85,285 (~US$11,000 or E9500) with darbepoetin alfa. Drug acquisition and administration accounted for 81 % and 67% of the total cost of epoetin alfa and darbepoetin alfa therapy, respectively; the remainder of the total cost was for hospitalization and transfusions.     

Darbepoetin alfa in lung cancer patients on chemotherapy: a retrospective comparison of outcomes in patients with mild versus moderate-to-severe anaemia at baseline

Goals Currently, there is some debate concerning the haemoglobin level at which treatment of anaemia with erythropoiesis-stimulating agents should be initiated in cancer patients on chemotherapy. We report several analyses of data from a phase III trial of darbepoetin alfa versus placebo, comparing outcomes for patients with mild and moderate-to-severe anaemia.Patients and methods Data were obtained from a phase III trial of darbepoetin alfa versus placebo in anaemic patients with lung cancer receiving chemotherapy (n=314). Outcomes were compared for patients with baseline haemoglobin 10–11 g/dl and <10 g/dl.Results Darbepoetin alfa significantly reduced transfusions compared with placebo, irrespective of haemoglobin level at treatment initiation. For patients with baseline haemoglobin <10 g/dl, 31% and 59% of those receiving darbepoetin alfa and placebo, respectively, required a transfusion from week 5 to the end of the treatment phase (P<0.038). For patients with baseline haemoglobin 10 g/dl, the proportions were 15% and 41%, respectively (P<0.001). Darbepoetin alfa also improved fatigue compared with placebo in both haemoglobin categories.Conclusions These findings show that initiating treatment at haemoglobin levels both <10 g/dl and 10–11 g/dl results in substantial clinical benefits, supporting the use of erythropoietic therapy also in patients with mild anaemia.J. Vansteenkiste is the beneficiary of the Amgen Fund in Supportive Cancer Care at the Catholic University, Leuven, Belgium.This work was supported by Amgen Inc., Thousand Oaks, California, USA     

Darbepoetin alfa in the treatment of chemotherapy-induced anaemia

Background: Darbepoetin alfa is an erythropoiesis-stimulating agent (ESA), with a longer half-life than previous recombinant human erythropoietins. After its initial development for anaemia due to renal insufficiency, an extensive clinical trial program has defined its role in cancer patients. Objective/methods: Review of the initial registration studies, further development and recent progress, guidelines for use in clinical practice (EORTC, ASCO/ASH), and specific focus on recent safety concerns. Results: Darbepoetin alfa significantly decreases the number of red blood cell transfusions in patients with chemotherapy-induced anaemia, and has been shown to improve health-related quality of life in several studies. The prolonged half-life allows a prolonged dosing interval. Administration every three weeks, a suitable schedule to synchronise with day 1 of many chemotherapy regimens, is as efficient as the initially registered weekly administration. Recent data strongly suggest that the addition of intravenous iron improves haemoglobin response rates. The use of these agents in clinical practice has to be according to the guidelines. Recent safety data reported a negative effect on survival when ESAs were used to treat anaemia that was either not chemotherapy related, or when used to maintain high levels of haemoglobin and prevent anaemia. All of these studies were not in accordance with existing guidelines, while safety data from clinical trials using ESAs according to the guidelines remain reassuring. Conclusion: Darbepoetin alfa has a well defined place in the treatment of chemotherapy-induced anaemia, and is safe when used in line with existing guidelines. Recent safety signals on cancer outcomes in studies not in accordance with these guidelines illustrate the need for further research into the complex interaction between anaemia and tumour hypoxia in cancer patients.     

Darbepoetin alfa: a new approach to the treatment of chemotherapy-induced anaemia

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

Patient and caregiver time burden associated with anaemia treatment in different patient populations

Goals 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.Materials and methods 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.Results 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.Conclusions Reducing the number of clinic visits needed for anaemia treatment by using darbepoetin alfa may benefit patients.     

Unit dosing of darbepoetin alfa for thetreatment of anemia in patients with end-stage renal disease being switched from recombinant human erythropoietin: Results of a phase IIIb, 27-week, multicenter, open-label study in Greek patients

Background:

Darbepoetin alfa is an erythropoietis-stimulating glycoprotein with a ∼3-fold longer t1/2 and greater biological activity compared with recombinant human erythropoietin (rHuEPO).

Objective:

The objective of this study was to evaluate the efficacy andtolerability of long-term (24-week) darbepoetin alfa treatment in maintaining hemoglobin (Hb) concentrations in the target range of 10 to 13 g/dL in patients undergoing dialysis; the patients were switched from rHuEPO to a less-frequent dosing regimen of darbepoetin alfa without an increase in dose.

Methods:

In this Phase IIlb, open-label, multicenter study, patients withend-stage renal disease (ESRD) undergoing dialysis who were receiving rHuEPO BIW or TIW at baseline were switched to darbepoetin alfa QW; patients receiving rHuEPO QW were switched to darbepoetin alfa Q2W Administration of darbepoetin alfa was by the same route as previous rHuEPO administration (IV or SC). Patients received darbepoetin alfa for 24 weeks, including a 20-week drug titration period followed by a 4-week, stable-dose evaluation period. The mode, dose, and frequency of administration of darbepoetin alfa were compared with those of baseline rHuEPO. Tolerability assessment was based on spontaneous reporting and laboratory tests (hematology, vital sign measurement, iron status, and biochemistry).

Results:

The study comprised 173 patients who were divided into 2 groups by route of administration (IV group, n = 146; SC group, n = 27). Mean (SE) adjusted increases in Hb concentration from baseline to the evaluation period for patients receiving darbepoetin alfa QW were 0.94 (0.32) g/dL and 0.38 (0.30) g/dL for the IV or SC routes, respectively (P = 0.004 and NS, respectively). For patients receiving darbepoetin alfa Q2W the mean (SE) adjusted increases in Hb concentration were 0.08 (0.53) g/dL and 0.48 (0.35) g/dL for the IV and SC routes, respectively (both, P = NS). No significant differences in IV/SC dose ratio were observed between the 2 routes of administration. In addition, no increases in darbepoetin alfa dose were observed. The most commonly reported adverse events were hypertension (8 patients [5%]) and vascular access thrombosis (4 [2%]). The incidence of treatment-related adverse events was 6 (3%).

Conclusions:

Darbepoetin alfa effectively maintained Hb concentrations within the target range without an increase in dose, even at a reduced dosing frequency. Overall, darbepoetin alfa was well tolerated.     

Darbepoetin alfa in anemia of myelodysplastic syndromes: present and beyond

Importance of the field: Anemia is the leading clinical manifestation in myelodysplastic syndromes (MDS), significantly altering quality of life. Darbepoetin alfa has recently been added to the armentarium of erythropoiesis stimulating agents (ESAs) for the treatment of anemia in MDS.

Areas covered in this review: We review here the efficacy and safety data on the use of darbepoetin alfa in the management of anemia in MDS patients. Published reports covering the period from 2005 till today were reviewed, as well as updated guidelines on the use of ESAs.

What the reader will gain: Darbepoetin alfa administered, during correction phase, once a week or at longer intervals, yielded erythroid response rates comparing favourably with those obtained with recombinant human erythropoietin (rHuEPO) in lower-risk MDS. During maintenance phase, intervals between injections can be further increased in many responders. Quality of life was consistently improved in responders and the drug was overall well tolerated.

Take home message: Those results, together with recent studies showing improved long-term outcomes in responders, support the use of darbepoetin, among other ESAs, for the treatment of anemia of lower-risk MDS, as recommended by international guidelines.     

The National Anaemia Action Council, Inc.: the primary North American resource for anaemia education and research

The mission of the National Anaemia Action Council, Inc. (NAAC) is to raise the awareness of health care professionals and the public regarding the prevalence, symptoms, consequences and under-treatment of anaemia. This editorial illustrates the goals and objectives of NAAC, and depicts past, present and future educational and research projects and findings. NAAC resources in anaemia-related education and research are described in detail.     

Hemoglobin Stability and Patient Compliance With Darbepoetin Alfa in Peritoneal Dialysis Patients After the Implementation of the Prospective Payment System

PurposeSince the Centers for Medicare & Medicaid Services implemented the End-Stage Renal Disease Prospective Payment System, dialysis providers have increasingly focused on balancing resource utilization and quality outcomes for the treatment of anemia in patients undergoing peritoneal dialysis. Limited data exist regarding anemia management outcomes for these patients in US-based dialysis centers after the implementation of the new payment system.MethodsThis was a retrospective, observational, cohort study of stable PD patients with end-stage renal disease who received darbepoetin alfa for anemia management over a 15-month period (April 1, 2011–June 29, 2012). The medication was administered by staff in the home-training unit instead of being self-administered at home. The primary end point was mean quarterly hemoglobin (Hb) levels. Variability in Hb levels was assessed over the 5 quarters by using repeated measures ANOVA to test for differences in the observed mean SDs.FindingsIn the 139 adult patients on stable peritoneal dialysis and meeting the eligibility criteria, mean (SD) Hb level by quarter was 10.8 (1.2) g/dL in quarters 2 and 3 of 2011, 10.5 (1.1) g/dL in quarter 4 of 2011, and 10.4 (1.1) g/dL in quarters 1 and 2 of 2012. Hb levels were stable (mean SDs, 0.58–0.72) over the 5 quarters of the study. Patient compliance with attendance for all scheduled home training unit visits was 84%.ImplicationsPD patients who underwent darbepoetin alfa administration and twice-monthly laboratory testing in the home-training unit had stable Hb levels. Despite more frequent center visits compared with a home-administered approach, patient compliance was high.     

The background and methodology of the Anaemia Cancer Treatment (A.C.T.) study: a global retrospective study of practice patterns and outcomes in the management of anaemia in cancer patients and their congruence with evidence-based guidelines

Goal The benefit of supportive care with erythropoiesis-stimulating agents (ESAs) for patients with cancer-related anaemia is well known. However, the European Cancer Anaemia Survey (ECAS, data from 2001) showed that about 60% of cancer patients with anaemia do not receive any treatment. Since ECAS, evidence-based guidelines have provided recommendations for ESA use, but it is not known to what extent current treatment patterns follow these guidelines. To address this issue, the Anaemia Cancer Treatment (A.C.T.) study was initiated. The background to the development of the A.C.T. study and study methodology are described. Materials and methods The A.C.T. study is a global, retrospective, pharmacoepidemiologic study of at least 2,560 medical records of anaemic patients with cancer who were previously treated with an ESA from a minimum of 186 centres. Records from patients aged greater than or equal to 18 years with a diagnosis of solid tumour or myeloma or lymphoma and who were started on ESAs 3–12 months before inclusion and followed for 8–10 weeks will be eligible. Factors associated with ESA non-responsiveness will also be evaluated. Main results Completion of the European phase of the study is anticipated in late 2007 with the rest of the world closing in late 2007 or early 2008. Publication of findings is anticipated in 2008. Conclusions By examining the extent to which anaemia management in clinical practice is congruent with best practice guidelines, the A.C.T. study will provide a further foundation for the development of evidence-based supportive cancer care.     

Cancer disclosure: experiences of Iranian cancer patients

This study explored Iranian patients' experiences of cancer disclosure, paying particular attention to the ways of disclosure. Twenty cancer patients were invited to participate in this qualitative inquiry by research staff in the clinical setting. In-depth, semistructured interview data were analyzed through content analysis. The rigor of the study was established by principles of credibility, transferability, dependability, and confirmability. Four themes emerged: the atmosphere of non-disclosure, eventual disclosure, distress in knowing, and the desire for information. Non-disclosure was the norm for participants, and all individuals involved made efforts to maintain an atmosphere of non-disclosure. While a select few were informed of their diagnosis by a physician or another patient, the majority eventually became aware of their diagnosis indirectly by different ways. All participants experienced distress after disclosure. The participants wanted basic information about their prognosis and treatments from their treating physicians, but did not receive this information, and encountered difficulty accessing information elsewhere. These challenges highlight the need for changes in current medical practice in Iran, as well as patient and healthcare provider education.     

Incidence, pathophysiology and treatment of cervical cancer

Cervical cancer is the third most common cancer affecting women. While not in itself a sexually transmitted disease, cervical cancer is linked to the presence of the human papilloma virus, which is sexually transmitted. Survival rates are significantly higher where diagnosis is early, and a national screening programme has reduced mortality in the UK. However, uptake is low in some groups and nurses have a role in increasing uptake.     

肺癌患者血浆纤维蛋白原、D-二聚体水平与预后的相关性研究

目的:探讨肺癌患者血浆纤维蛋白原、D-二聚体水平与预后的相关性。方法:测定60例肺癌患者(肺癌组)及20例健康体检者(对照组)血浆纤维蛋白原、D-二聚体水平并进行对比分析。结果:肺癌组血浆纤维蛋白原、D-二聚体水平高于对照组(P<0.05),肺癌组血浆纤维蛋白原、D-二聚体水平与病理类型、肿瘤大小、TNM分期之间无明显关系。肺癌患者血浆纤维蛋白原、D-二聚体水平与生存期呈显著负相关。结论:肺癌患者血液处于高凝状态,血浆纤维蛋白原、D-二聚体水平与患者的预后密切相关。抗凝治疗对控制肺癌患者病情的发展及预后可能有重要的临床意义。     

Incidence and prognosis of cancer associated with bilateral venous thrombosis: a prospective study of 103 patients

Summary.  Background : A strong association between bilateral deep vein thrombosis (DVT) and cancer had been found in one retrospective study. To confirm this finding, consecutive patients with an objective diagnosis of bilateral DVT were followed over 12 months. Patients and methods : One-hundred and three patients, hospitalized for bilateral DVT, were included in the study. Twenty-six patients (25.2%) were already known to have a cancer, 26 (25.2%) had a previous history of venous thromboembolic disease, 44 (42.7%) had a symptomatic pulmonary embolism. The patients were scheduled to be prospectively followed up at 3, 6 and 12 months as outpatients. Information on recurrence, evidence of a new overt cancer and the cause of death were recorded for all patients. Results : A new cancer was diagnosed in 20 (26%) of the 77 patients without known cancer at admission. The risk of cancer was significantly more important in idiopathic thrombosis than in patients with secondary thrombosis (40.5% vs. 12.5%; odds ratio 4.8, 95% confidence interval 1.4, 18.8). Seventy percent of the cancers discovered had already spread. Age, gender, presence of pulmonary embolism, recurrence and location of the thrombosis were not statistically associated with the risk of cancer. The 1-year survival rates of patients with a previously known cancer and patients with a newly discovered cancer were, respectively, 26% and 35% ( P =  0.33). Conclusion : Bilateral DVT is a significant risk indicator of malignancy. Cancer is present in 45% of patients with bilateral DVT and is associated with a poor prognosis.     

TURBT术后吡柔比星灌注治疗对浅表性膀胱癌患者VEGF、FGF、MMPs及预后的影响

目的探讨尿道膀胱肿瘤电切术(TURBT)术后吡柔比星灌注治疗对浅表性膀胱癌患者血管内皮生长因子(VEGF)、成纤维细胞生长因子(FGF)、基质金属蛋白酶(MMPs)及预后的影响。方法选取2015年3月至2016年10月我院泌尿科收治的92例浅性膀胱癌患者,按照随机数字表法分为试验组(46例,TURBT+吡柔比星灌注治疗)与对照组(46例,TURBT)。比较两组患者治疗前、后的血清相关因子水平及预后情况。结果治疗后,两组的VEGF、a FGF、b FGF、MMP-2、MMP-9水平均降低,且试验组明显低于对照组,差异具有统计学意义(P<0.05)。治疗后24、36个月,试验组的生存率均显著高于对照组,差异具有统计学意义(P<0.05)。治疗后12、24、36个月,试验组的复发率均显著低于对照组,差异具有统计学意义(P<0.05)。试验组的不良反应总发生率为8.70%,明显低于对照组的23.91%,差异具有统计学意义(P<0.05)。结论浅表性膀胱癌患者TURBT术后吡柔比星灌注治疗,能够显著降低血清相关因子水平,改善预后效果,且安全性更高,值得临床推广应用。     

Diagnostic workup of cancer in patients with new-onset anaemia: a Danish cohort study in general practice

BackgroundAnaemia is associated with adverse outcomes, including increased morbidity and all-cause mortality. Diagnostic workup of patients with anaemia is essential to detect underlying disease, especially undiagnosed malignancy.ObjectiveTo describe the cancer-relevant diagnostic workup in patients with new-onset anaemia detected in general practice. An additional aim was to analyse associations between patient characteristics and the diagnostic workup.DesignObservational population-based cohort study using electronic laboratory and register data.SettingDanish general practice.SubjectsPatients aged 40–90 years with new-onset anaemia (no anaemia in the preceding 15 months) detected in general practice. Patients were identified in Danish laboratory information systems and nationwide registries in 2014–2018.Main outcome measuresWe measured the proportion of patients receiving predefined diagnostic investigations, that is, cancer patient pathway, colonoscopy, gastroscopy, computerised tomography (CT) scan, faecal test for haemoglobin, and bone marrow examination within three months of the anaemia index date.ResultsWe included 59,993 patients, and around half of the patients with ‘iron deficiency anaemia’, ‘anaemia of inflammation’, or ‘combined inflammatory iron deficiency anaemia’ had no cancer-relevant diagnostic investigations performed. Patients aged 60–79 years and patients with severe anaemia were more likely to have investigations performed, while patients with comorbidity were less likely to have investigations performed.ConclusionAround half of the patients with anaemia subtypes that may indicate underlying cancer had no cancer-relevant diagnostic investigations performed. This may represent missed diagnostic opportunities. Future interventions are needed to improve the diagnostic workup of cancer in patients with anaemia, for example, laboratory alert systems and clinical decision support.

KEY POINTS

• The general practitioners are often the first to detect anaemia and its underlying disease (e.g. undiagnosed malignancy).
• Large-scale studies are needed on the diagnostic workup of patients with anaemia in general practice in relation to an underlying malignancy.
• This study shows that the majority of patients with anaemia had no cancer-relevant diagnostic investigations performed, which may cause diagnostic delay.
• Interventions seems needed to improve the diagnostic workup of cancer in these patients to ensure timely diagnosis.

     

The incidence,risk factors and prognostic implications of venous thromboembolism in patients with gastric cancer

Summary. Background: Data on venous thromboembolism (VTE) in gastric cancer (GC) are very scarce. Objective: To investigate the incidence, risk factors and prognostic implications of VTE in Asian GC patients. Methods: Prospective databases containing clinical information on GC patients (n = 2,085) were used. Results: The 2‐year cumulative incidences of all VTE events were 0.5%, 3.5% and 24.4% in stages I, II–IV(M0) and IV(M1), respectively. Advanced stage, older age and no major surgery were independent risk factors for developing VTE. When the VTE cases were classified into extremity venous thrombosis (EVT), pulmonary thromboembolism (PTE) or intra‐abdominal venous thrombosis (IVT), IVTs (62%) were more common than EVTs (21%) or PTEs (17%). Although peri‐operative pharmacologic thromboprophylaxis was not routinely administered, the VTE incidence after major surgery was only 0.2%. During chemotherapy, EVT/PTE developed more frequently than IVT (54% vs. 19%); however, during untreated or treatment‐refractory periods, IVT developed more frequently than EVT/PTE (69% vs. 36%). In multivariate models, the development of EVT/PTE was a significant predictor of early death when compared with no occurrence of VTE (P < 0.05). However, IVT did not affect survival. Conclusion: This is the largest study that specially focused on VTE in GC and the VTE incidence in Asian GC patients was first demonstrated. Considering the low incidence of post‐operative VTE development, the necessity of peri‐operative pharmacologic thromboprophylaxis should be evaluated separately in Asian patients. The clinical situation of the development of EVT/PTE and IVT differed. Only EVT/PTE had an adverse effect on survival and IVT had no prognostic significance.