Multivariate regression analyses of data from a randomised,double-blind,placebo-controlled study confirm quality of life benefit of epoetin alfa in patients receiving non-platinum chemotherapy

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.     

Improvement in quality of life for cancer patients treated with epoetin alfa

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.     

Darbepoetin alfa: potential role in managing anemia in cancer patients

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

Epoetin alfa in platinum-treated ovarian cancer patients: results of a multinational, multicentre, randomised trial

This multicentre, open-label, controlled clinical trial assessed the effects of epoetin alfa treatment on haematologic and quality of life (QOL) parameters in 182 anaemic (Hb< or = 12 g dl(-1)) ovarian cancer patients receiving platinum chemotherapy. Patients were randomised 2 : 1 to receive epoetin alfa 10,000-20 000 IU three times weekly plus best standard treatment (BST) or BST only. Main study end points were changes from baseline in haemoglobin (Hb) level, transfusion requirements, and QOL. For the epoetin alfa group, mean Hb increased by 1.8 g dl(-1) by weeks 4-6 and was significantly increased from baseline through study end (P<0.001). The mean change in Hb from baseline was significantly (P<0.001) greater for epoetin alfa than BST patients at all post-baseline evaluations. Significantly fewer epoetin alfa than BST patients required transfusion(s) after the first 4 weeks of treatment (7.9 vs 30.5%; P<0.001). Also, significant (P< or = 0.04) differences favouring the epoetin alfa group over the BST group were found for all three median CLAS scores (Energy Level, Ability to Do Daily Activities, Overall QOL) and the median average CLAS score during chemotherapy. These findings support use of epoetin alfa to increase Hb levels, reduce transfusion use, and improve QOL in anaemic ovarian cancer patients receiving platinum chemotherapy.     

Epoetin alfa therapy for patients with hematologic malignancies and mild anemia

Anemia has been reported in approximately 40%-70% of patients with hematologic malignancies, with severity depending on the type and stage of disease and whether the patient has received myelosuppressive chemotherapy. Growing evidence supports the role of epoetin alfa in correcting anemia and improving quality of life (QOL) in patients with hematologic malignancies. Clinical practice guidelines recommend the use of epoetin alfa in patients with cancer-related anemia (including patients with hematologic malignancies) and hemoglobin levels < or =10 g/dL. Epoetin alfa treatment is optional for patients with cancer-related anemia and hemoglobin levels>10 g/dL and <12 g/dL, depending on clinical circumstances. A prospective, open-label, randomized trial evaluating hematologic response, transfusion use, and QOL after immediate or delayed epoetin alfa treatment in mildly anemic patients (hemoglobin< or =12 g/dL) undergoing chemotherapy for chronic lymphocytic leukemia, multiple myeloma, or lymphoma was recently completed. Study objectives included determining any correlation between changes in hemoglobin level and QOL and assessing any correlation between QOL measures and health care resource use. Interim results suggest that epoetin alfa treatment in patients with hematologic cancers and hemoglobin< or =12 g/dL who are receiving chemotherapy increases hemoglobin, functional capacity, well-being, work and productivity, and health resource use. Further evaluation of alternative epoetin alfa dosing schedules and use of epoetin alfa in treating anemia in patients with specific hematologic malignancies is ongoing.     

The impact of weekly dosing of epoetin alfa on the haematological parameters and on the quality of life of anaemic cancer patients

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.     

Hepcidin在恶性血液病贫血患者中的表达及临床意义

目的:探讨铁调素(hepcidin)在恶性血液病贫血患者中的表达,并对hepcidin与白细胞介素6 (interleukin-6,IL-6)、血红蛋白(hemoglobin,Hb)、血清铁和铁蛋白表达水平进行相关性分析。方法:收集80例恶性血液病贫血患者外周血,分别检测hepcidin、IL-6、Hb、血清铁和铁蛋白的表达水平,并以30例健康人群作为对照;使用SPSS 21.0软件对实验结果进行统计学分析。结果:恶性血液病贫血患者血清中hepcidin、IL-6、Hb、血清铁和铁蛋白的表达量分别为(61.93±19.98) μg/L、(5.56±1.17) ng/L、(96.68±12.35) g/L、(9.85±1.09) μmol/L和329.42(299.70~459.06) μg/L;健康对照组相对应的表达量分别为(21.35±7.38) μg/L、(2.52±1.28) ng/L、(140.07±7.71) g/L、(19.95±4.25) μmol/L和95.72(76.56~131.42) μg/L,两组差异均具有统计学意义(P<0.01)。恶性血液病男性贫血患者中hepcidin、IL-6和Hb的表达量均高于女性患者(P<0.05);中度贫血患者hepcidin、IL-6和铁蛋白的表达量均高于轻度贫血患者,Hb和血清铁表达量低于轻度贫血患者(P<0.01)。线性回归分析结果显示hepcidin与Hb、血清铁含量呈负相关,与IL-6、铁蛋白含量呈正相关(P<0.05)。结论:Hepcidin在恶性血液病贫血患者中高表达,并与贫血程度相关,提示hepcidin在恶性血液病贫血发生中具有重要作用。     

Epoetin alfa therapy increases hemoglobin levels and improves quality of life in patients with cancer-related anemia who are not receiving chemotherapy and patients with anemia who are receiving chemotherapy.

PURPOSE: To evaluate efficacy, safety, and quality of life (QOL) changes with epoetin alfa therapy for anemia in patients with nonmyeloid malignancies. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Weekly epoetin beta maintains haemoglobin levels and improves quality of life in patients with non-myeloid malignancies receiving chemotherapy

Objective: This study was aimed at investigating the effectiveness andsafety of once-weekly epoetin beta for anaemic cancer patientsreceiving chemotherapy. Methods: A total of 104 patients with a haemoglobin level of 11.0 g/dLwere enrolled. Patients received a once-weekly subcutaneousdose of 36 000 IU epoetin beta for 12 weeks. If the increasein the haemoglobin level was <1.0 g/dL after 6 weeks, ora red blood cell transfusion was required between days 15 and42, the dose of epoetin beta was increased to 54 000 IU fromthe subsequent week. The primary endpoint was the percentageof patients who achieved a haemoglobin increase of 2.0 g/dL;the haemoglobin response rate. Quality of life (QOL) was assessedusing the Functional Assessment of Cancer Therapy-Anaemia (FACT-An)questionnaire. Results: The haemoglobin response rate was 66.3% among the 98 patients(breast cancer: n = 25; malignant lymphoma: n = 21; ovariancancer: n = 20; lung cancer: n = 15; other cancers: n = 17)assessable for a haemoglobin response. Thirty-nine patients(39.8%) required a dose escalation to 54 000 IU. At the endof the study, QOL assessable patients (n = 96) showed a meanimprovement in the FACT-An total fatigue subscale score (FSS)of 0.3 points from baseline. Patients with a haemoglobin responsehad a mean change in the total FSS of +3.2, compared with –3.4for patients without a haemoglobin response. No serious adverseevent of epoetin beta was observed. Conclusions: Epoetin beta administered at an initial dose of 36 000 IU once-weeklywas well tolerated, with increased haemoglobin levels and improvedQOL in anaemic cancer patients receiving myelosuppressive chemotherapy.     

Darbepoetin alfa for the treatment of cancer-related anemia: an update

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

Darbepoetin alfa in the treatment of anemia in cancer patients undergoing chemotherapy

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

Effect of epoetin alpha therapy on cognitive function in anaemic patients with solid tumours undergoing chemotherapy

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.     

c-FLIP mRNA 在恶性血液病中的表达及其意义

目的：探讨C—FLIPmRNA在恶性血液病中的表达及其意义。方法：用采用半定量逆转录聚合酶链反应（RT—PCR）检测42例恶性血液病骨髓单个核细胞C—FLIPmRNA的表达。包括急性白血病（AL）27例，其中初治21例及复发和完全缓解（CR）后AL各3例、慢性粒细胞性白血病（CML）5例、慢性中性粒细胞性白血病（CNL）1例和慢性淋巴细胞性白血病（CLL）4例，多发性骨髓瘤（MM）3例，骨髓增生异常综合征-难治性贫血伴原始细胞增多2型（MDS—RAEB-2）2例。结果：在初治和复发AL、初治CML、CNL、CLL、MDS—RAEB-2、MM中C—FLIPmRNA均呈异常增高表达，初治AL中c—FLIPmRNA的表达与复发AL比较差异无统计学意义（P〉0．05），其FAB各亚型之间的表达差异亦无统计学意义（P〉0．05）。初治AL与CLLC—FLIPmRNA的表达显著高于初治CML（P〈0．001），但初治AL与初治CLLE魄磋淠呒统计学意义（P〉0．05）。MDS—RAEB-2、MMC—FLIPmRNA的表达与AL的cFLIPmRNA表达均无统计学差异（P〉0．05）。对照组和CR后AL均为阴性表达。C—FLIPmRNA的表达与初治AL患者年龄、性别、初诊白细胞数、LDH以及核型、免疫表型无关。初治未达CR的AL患者其c—FLIPmRNA表达高于CR者，但并无统计学意义（尸〉0．05）。结论：恶性血液病C—FLIPmRNA的表达异常增高。C—FLIPmRNA能反映恶性血液病骨髓细胞的凋亡抑制情况，并与恶性血液病的类型、疾病状态、临床疗效和预后密切相关。     

Changes in mortality associated with different hematologic malignancies during the pandemic in the United States

Patients with hematologic malignancies are at increased risk of adverse COVID-19 outcomes; nonetheless, only sparse population-based data are available on mortality related to hematologic cancers during the pandemic. Number of deaths and age-standardized mortality rates for specific hematologic malignancies selected either as the underlying cause of death (UCOD), or mentioned in death certificates (multiple causes of death-MCOD) were extracted from the US National Center for Health Statistics, CDC WONDER Online Database. Joinpoint analysis was applied to identify changes in mortality trends from 1999 to 2021, and to estimate the annual percent change with 95% Confidence Intervals (CI) across time segments. Among the most common malignancies, chronic lymphocytic leukemia showed marked peaks in the monthly number of deaths attributed to COVID-19 during epidemic waves; acute myeloid leukemia showed the least variation, and non-Hodgkin lymphoma and multiple myeloma were characterized by an intermediate pattern. Age-standardized death rates relying solely on the UCOD did not show significant variations during pandemic years. By contrast, rates based on MCOD increased by 14.0% (CI, 10.2–17.9%) per year for chronic lymphocytic leukemia, by 5.1% (CI, 3.1–7.2%) for non-Hodgkin lymphoma and by 3.2% (CI, 0.3–6.1%) per year for multiple myeloma. Surveillance of mortality based on MCOD is warranted to accurately measure the impact of the COVID-19 pandemic and of other epidemics, including seasonal flu, on patients with hematologic malignancies, and to assess the effects of vaccination campaigns and other preventive measures.     

A randomized, multicenter study of subcutaneous and intravenous darbepoetin alfa for the treatment of chemotherapy-induced anemia.

BACKGROUND: This randomized, open-label study evaluated the efficacy, safety and pharmacokinetics of darbepoetin alfa administered intravenously (i.v.) or subcutaneously (s.c.) in chemotherapy-induced anemia. PATIENTS AND METHODS: Patients received darbepoetin alfa i.v. (n=59) or s.c. (n=59) at a dose of 4.5 mug/kg once weekly for 6 weeks (correction phase) followed by 4.5 mug/kg once every 3 weeks for the remainder of the 18-week treatment period (maintenance phase). RESULTS: During the correction phase, the mean [95% confidence interval (CI)] change in hemoglobin (intention-to-treat) was 1.1 (0.6-1.5) g/dl in the i.v. group and 1.3 (0.9-1.7) g/dl in the s.c. group; using available data, the mean change was 1.4 (1-1.9) g/dl and 1.6 (1.2-2) g/dl, respectively. The percentage (95% CI) of patients maintaining hemoglobin (i.e. average decrease < or =0.5 g/dl) during the maintenance phase was similar between the i.v. (82%; 95% CI 66% to 92%) and s.c. (80%; 95% CI 66% to 90%) groups. Thirty-five per cent (95% CI 20% to 50%) of patients in the i.v. group and 32% of patients in the s.c. group (95% CI 18% to 45%) received red blood cell transfusions during week 5 to the end of the treatment period. Darbepoetin alfa was well tolerated in both groups. No significant difference (P=0.36) in weekly darbepoetin alfa serum concentrations was observed between groups. CONCLUSIONS: Darbepoetin alfa can be administered i.v. or s.c. at equal doses for the treatment of anemia in this setting.     

A clinical model for quality of life assessment in cancer patients receiving chemotherapy

Background:The pattern of symptoms experienced by cancer patientsduring chemotherapy is very complex. Consequently, quality of life (QOL)assessment has to be carefully planned to capture clinically relevant changes. Patients and methods:A clinical model of changes in symptomsexperienced by symptomatic metastatic patients during several courses ofchemotherapy has been developed. The model differentiates cancer-relatedsymptoms, acute side-effects, chronic side-effects and symptoms not relatedto cancer. The model was used to predict changes in each of these four symptomgroups. Three time points were selected (post-cycle 2, pre-cycle 3, post-cycle5) and an appropriate window around each time point was set. The modelpredictions were tested empirically with 56 patients with advanced ovariancancer who completed the EORTC QLQ-C30 plus disease specific items during asix-cycle course of chemotherapy. Results:The changes observed in the sample were in accordancewith the changes predicted by the clinical model. Results from patients whodid not complete the questionnaire within the specified time windows tendedto dilute the findings from the group who did. Conclusions:A clinical model is useful in the planning of QOLassessments in order to capture clinically relevant effects. Such models alsofacilitate the interpretation of QOL studies, particularly when cyclicshort-term effects and chronic side-effects are overlaid on disease symptoms,as is the case with chemotherapy for cancer.