Treatment of anaemia in cancer patients: implications for supportive care in the National Health Service Cancer Plan

SUMMARY

The National Health Service (NHS) Cancer Plan published in 2000 has a short-term focus on the most pressing problems of improving survival rates and replacing equipment. It also mentioned as a target 'improved quality of life for those affected by cancer'. Continuity of care for longer-term care programmes was seen predominantly in terms of palliative care. Recent National Institute for Clinical Excellence (NICE) reports may have reinforced this approach by focussing on the clinical and cost effectiveness of chemotherapy for late-stage cancer. The impact on local decision-makers has been that drug funds have been prioritised for use on survival-enhancing interventions, with few resources left for short and longer-term supportive care targeted primarily on improving quality of life. Within supportive care, resources are particularly limited for funding treatments such as erythropoietin for the management of cancer-related anaemia, a common and very debilitating side-effect of intensive therapy. The need for a re-focusing on supportive care is associated with cancer becoming, in many instances, a longer-term illness. The prevalence of

cancer is rising markedly due to increased survival rates. However, this creates a new challenge of reducing disability and improving quality of life. In surveys, patients have rated fatigue associated with anaemia as one of the most debilitating effects of their cancer and its treatment with chemotherapy. This paper reviews the evidence demonstrating the quality of life benefits of erythropoietin, and then considers the policy constraints that have limited the adoption of this treatment within the NHS. Through co-ordinated planning there are opportunities for cancer networks and primary care trusts (PCTs) working with cancer centres to develop more support in ways which are feasible and fundable. The case is argued that PCTs and cancer networks, in implementing the Cancer Plan locally, need to integrate short- and longer-term supportive care into their cancer service development plans, and recognise the importance of anaemia management as an integral part of this. Lessons can be learnt from UK renal services where anaemia management with erythropoietin is standard practice.     

Evaluation of the effect of erythropoietin + corticosteroid versus corticosteroid alone in methanol-induced optic nerve neuropathy

Purpose: Following methanol intoxication, optic nerve neuropathy may occur, which is currently treated by different therapeutic regimens. Erythropoietin (EPO) has recently been introduced as a good therapeutic option in methanol-induced optic neuropathy. The aim of the current study was to evaluate the efficacy of EPO in improvement of the visual disturbances in methanol-intoxicated patients.

Materials and methods: In a case-control study, all patients who had referred to our toxicology centre with confirmed diagnosis of methanol toxicity were considered to be included. Of them, those who had referred with visual disturbances, survived, and their visual disturbances had not improved after haemodialysis were entered. Cases received EPO and corticosteroids while controls only received corticosteroids. They were then compared regarding their visual outcome.

Results: All five patients in the control group mentioned that after discharge, their visual acuity had improved while in the cases, three mentioned visual improvement, two mentioned their visual acuity had deteriorated after discharge, two mentioned no change in their visual acuity and three mentioned that their visual acuity had first improved but then deteriorated with a mean two-month interval period. In fundoscopic evaluations, two controls had normal fundospcopy while eight cases had abnormal fundoscopy (p?=?0.055).

Conclusions: Protective effect of EPO on methanol-induced optic nerve may be strong at the beginning of the intervention but is probably transient.     

Hemoglobins With High Oxygen Affinity Leading to Erythrocytosis. New Variants and New Concepts

This review brings some new insights on erythrocytosis of genetic origin related to problems of oxygen delivery by hemoglobin (Hb). A few molecular mechanisms are individualized among the about 100 Hb variants that cause compensatory erythrocytosis. The most frequently observed structural modifications are localized in the α1β2 interface, or at the C-terminal. They impair formation of a stable T state. Others mutations modify directly or indirectly the surrounding of the heme and the site where oxygen binds. A special interest is brought to the dose effect considering the possibility for formation of hybrid tetramers with altered oxygen binding properties. Homozygous cases, and patients who are compound heterozygotes for a high oxygen affinity Hb and a thalassemia (thal), are discussed. Several examples are provided, specially documented for Hb Olympia [β20(B2)Val→Met] and Hb Saint Nazaire [β103(G5)Phe→Ile]. Other mechanisms leading to erythrocytosis are discussed, and finally, an algorithm is proposed for etiological diagnosis.     

Recombinant human erythropoietin attenuates weight loss in a murine cancer cachexia model

Background Within hypoxic tumor regions anaerobic dissimilation of glucose is the sole source of energy generation. It yields only 5% of the ATP that is normally gained by means of oxidative glucose catabolism. The increased need for glucose may aggravate cancer cachexia. We investigated the impact of recombinant human erythropoietin (RhEPO) and increased inspiratory oxygen concentrations on weight loss in tumor-bearing mice.Methods Fragments of the murine C26-B adenocarcinoma were implanted in 60 BALB/c-mice. The mice were divided into four groups and assigned to: (A) no treatment; (B) RhEPO- administration (25 IU daily from day 1–11, three times per week from day 12); (C) RhEPO and 25% oxygen; and (D) RhEPO and 35% oxygen. Three control groups of four healthy mice each received the same treatment as groups A, B, and D, respectively. Hematocrit and hemoglobin levels, tumor volume, and body weight were monitored. At day 17 the experiment was terminated and the serum lactate concentration was measured. The tumors were excised and weighed and, for each mouse, the percentage weight loss was calculated. The impact of tumor weight and the treatments on lactate concentration and weight loss was evaluated.Results Significant positive correlations were found between tumor weight and lactate concentration and between tumor weight and percentage weight loss. In the mice with the largest tumors, RhEPO displayed a significant weight loss-reducing effect, and a significant negative correlation was found between hemoglobin concentration and weight loss. An oxygen-rich environment did not appear to influence weight loss.Conclusion Anaerobic glycolysis in a growing C26-B tumor is related to weight loss. RhEPO administration results in a reduction of the percentage weight loss; this effect is probably mediated by an increased hemoglobin concentration.This study was financially supported by a grant from Ortho Biotech, a division of Janssen Cilag, Tilburg, the Netherlands     

Availability of iron and degree of inflammation modifies the response to recombinant human erythropoietin when treating anemia of chronic disease in patients with rheumatoid arthritis

Forty-six patients with rheumatoid arthritis (RA) and documented anemia of chronic disease (Hb <100/110 g/l) were randomized to receive either human recombinant erythropoietin (r-HuEPO, n = 36, 300 U/kg body weight) or placebo (n = 10) for 12 weeks in a multicenter study. An adequate response was defined as elevation of Hb≥120 g/l. Relevant clinical and laboratory assessments were made to evaluate efficacy and secure safety. A significant elevation in Hb from week 10 onwards was noted in twenty-six patients (five drop-outs) out of nine patients receiving placebo (one drop-out) (12±1.2 g/l vs 4±0.5 g/l; Hb elevation from 95 g/l to 107 g/l vs 93 g/l to 97 g/l, P<0.05). Only 14.6%, however, were considered responders according to preset criteria. In the responders a lower initial CRP, a significant reduction in ESR but not in CRP was seen compared to the remaining r-HuEPO group. A significant elevation of energy level was noted in the r-HuEPO group; otherwise, no differences in clinical variables were seen. No serious adverse effects were noted. When analyzing patients receiving oral iron in combination with r-HuEPO and adding five additional, openly selected patients receiving both adequate iron supplementation and r-HuEPO, there was a significant weekly elevation of Hb from week 8 onwards in favor of combination therapy over the ones only receiving r-HuEPO (18±1.1 g/l vs 7±1.1 g/l, P<0.05). The initial six responders had now reached ten of whom seven belonged to the combination therapy group. Response to r-HuEPO in RA patients appears to be dependent on availability of iron and on the degree of inflammation. If r-HuEPO treatment is considered, iron deficiency should always be corrected and strenous efforts should have been made to control the disease itself. Received: 21 February 1997 / Accepted: 21 April 1997     

生血宁片联合促红细胞生成素治疗维持性血液透析患者肾性贫血的临床观察

目的：探讨生血宁片联合促红细胞生成素治疗维持性血液透析患者肾性贫血的临床效果。方法选取该院住院治疗的维持性血液透析肾性贫血患者60例,随机分为治疗组与对照组,治疗组患者给予促红细胞生成素联合生血宁片进行治疗,对照组患者给予促红细胞生成素联合蔗糖铁进行治疗。对两组患者治疗前后的贫血指标、临床治疗效果和不良反应进行对比分析。结果两组患者在治疗前的贫血指标之间差异无统计学意义（P＞0.05）,治疗后两组患者的贫血指标较治疗前有显著变化（P＜0.05）,治疗组患者治疗后较对照组贫血指标差异有统计学意义（P＜0.05）。对照组患者通过治疗后的临床总有效率低于治疗组,两组之间差异有统计学意义（P＜0.05）。对照组患者的不良反应率高于治疗组,两组患者之间差异有统计学意义（P＜0.05）。对照组患者所使用的促红细胞生成素剂量明显高于治疗组,两组之间差异有统计学意义（P＜0.05）。结论采取生血宁片联合促红细胞生成素治疗维持性血液透析患者肾性贫血的临床效果较为良好,且安全性较高,值得在临床治疗中应用。     

血浆促红细胞生成素可作为预测增殖性糖尿病性视网膜病的危险因素

目的 探讨可作为预测增殖性糖尿病性视网膜病的危险因素.方法 选取2011年5月至2013年11月间在我院眼科怀疑为糖尿病视网膜病变患者168例作为研究对象,空腹抽取静脉血,送检验科实验室检测EPO、糖化血红蛋白、FBS、CRP水平、血脂、载脂蛋白A和B.采用t检验和x2检验、多因素logistic回归分析确定增殖性糖尿病性视网膜病发生的独立危险因素.结果 在怀疑为糖尿病视网膜病变患者168例中,测得患增殖性糖尿病性视网膜病患者28例,通过计算得出患者中增殖性糖尿病性视网膜病的患病率为16.67％.为了探讨PDR的危险因素,我们将全部PDR患者的可能危险因素纳入多因素logistic回归分析.结果表明,EPO(OR =0.31,95％CI:0.04～0.95,P=0.042)是预测增殖性糖尿病性视网膜病的独立危险因素.结论 血浆促红细胞生成素可作为预测增殖性糖尿病性视网膜病的危险因素.     

促红素对肝硬化大鼠血清—氧化氮含量的影响

目的探讨血红蛋白（Ｈｂ）对肝硬化大鼠血清一氧化氮（ＮＯ）含量及血流动力学的影响。方法应用５７Ｃｏ标记微球观察促红素长期治疗对肝硬化大鼠血流动力学参数的影响；应用荧光法测定大鼠血清ＮＯ含量。结果肝硬化大鼠全部出现高动力循环状态，且血清ＮＯ含量显著高于对照组、血Ｈｂ含量显著低于对照组；促红素治疗组，高动力循环状态明显改善，与未治疗组比较，Ｈｂ含量显著升高，血清ＮＯ含量显著降低。结论促红素致Ｈｂ增加，进而加速ＮＯ灭活对肝硬化高动力循环状态可能具有潜在治疗作用