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淋巴系统恶性肿瘤患者贫血管理的指南与建议

Guidelines and recommendations for the management of anaemia in patients with lymphoid malignancies.

作者信息

Henry David H

机构信息

Joan Karnell Cancer Center, Pennsylvania Hospital, Philadelphia, Pennsylvania 19106, USA.

出版信息

Drugs. 2007;67(2):175-94. doi: 10.2165/00003495-200767020-00002.

Abstract

Patients with lymphoid malignancies frequently require repetitive and intensive anticancer treatments to induce and maintain disease remission. Anaemia (haemoglobin [Hb] <12 g/dL) is a common and debilitating problem associated with both the malignancy itself and its treatment burden. Anaemia negatively impacts on all aspects of patient quality of life (QOL) and treatment outcomes and survival, particularly in this disease setting. Widely acknowledged goals of anaemia treatment include Hb correction to approximately 12 g/dL, reduction in transfusion requirements and optimisation of patient QOL. Since the introduction of recombinant human erythropoietic therapy, transfusion (once the only anaemia treatment option available) is now primarily reserved for non-responders or those with severe or life-threatening anaemia. Data from randomised, double-blind, placebo-controlled studies, and large, non-randomised, open-label, community-based studies, along with almost 15 years of practical experience, support the assertion that epoetin alfa administered at a dosage of 150-300 U/kg three times weekly or 40,000-60,000U once weekly, both of which are US FDA-approved dose administration schedules, can effectively and safely achieve anaemia treatment goals for the majority of patients with lymphoid malignancies. Data and practical experience collected over the last 5 years on another erythropoietic agent with a slightly longer half-life but lower binding affinity, darbepoetin alfa, show that this agent when administered according to the FDA-approved dose administration schedules (2.25-4.5 microg/kg once weekly or 500microg once every 3 weeks) or according to a commonly-administered dose in clinical practice (3.0-5.0 microg/kg once every 2 weeks) can also effectively and safely correct anaemia, reduce transfusion requirements and improve QOL in many patients with lymphoid malignancies. One comparative head-to-head trial suggested that epoetin alfa might be superior to darbepoetin alfa in anaemic cancer patients receiving chemotherapy with respect to timing and magnitude of Hb correction, although further study is necessary, especially concerning optimal dose administration. Alternative dose administration schedules, such as epoetin alfa 80,000U every 2 weeks from initiation or 80,000U every 3 weeks following initiation with once weekly administration and darbepoetin alfa 4.5 microg/kg every 3 weeks following initiation with once weekly administration, are being actively investigated with the goal of increased flexibility for patients and healthcare providers. The treatment of anaemia in patients with lymphoid malignancies is an important part of overall disease management, as evidenced by continuous investigation of existing erythropoietic agents and new agents. Although treatment guidelines issued by organisations such as the National Comprehensive Cancer Network (NCCN) and American Society of Hematology (ASH)/American Society of Clinical Oncology (ASCO) suggest intervention with erythropoietic therapy when Hb falls below 10-11 g/dL or based on clinical symptoms, data suggest that anaemia is vastly under-recognised and under-treated. Clearly, an update on the definition, identification and optimal management of anaemia in patients with lymphoid malignancies is warranted.

摘要

淋巴系统恶性肿瘤患者常常需要反复进行强化抗癌治疗,以诱导并维持疾病缓解。贫血(血红蛋白[Hb]<12 g/dL)是一个常见且使人虚弱的问题,与恶性肿瘤本身及其治疗负担都有关联。贫血会对患者生活质量(QOL)、治疗效果及生存的各个方面产生负面影响,在这种疾病背景下尤为如此。贫血治疗被广泛认可的目标包括将Hb纠正至约12 g/dL、减少输血需求以及优化患者的QOL。自从重组人促红细胞生成素疗法问世以来,输血(曾经是唯一可用的贫血治疗选择)现在主要留给无反应者或患有严重贫血或危及生命的贫血患者。来自随机、双盲、安慰剂对照研究以及大型非随机、开放标签、基于社区的研究的数据,以及近15年的实践经验,都支持这样的观点:以每周三次150 - 300 U/kg的剂量或每周一次40,000 - 60,000U的剂量使用促红细胞生成素α,这两种都是美国食品药品监督管理局(FDA)批准的给药方案,能够有效且安全地为大多数淋巴系统恶性肿瘤患者实现贫血治疗目标。过去5年收集到的关于另一种半衰期稍长但结合亲和力较低的促红细胞生成素药物——达贝泊汀α的数据和实践经验表明,按照FDA批准的给药方案(每周一次2.25 - 4.5 μg/kg或每3周一次500 μg)或按照临床实践中常用的剂量(每2周一次3.0 - 5.0 μg/kg)使用该药物,也能够有效且安全地纠正贫血、减少输血需求并改善许多淋巴系统恶性肿瘤患者的QOL。一项比较性的直接对比试验表明,在接受化疗的贫血癌症患者中,就Hb纠正的时间和幅度而言,促红细胞生成素α可能优于达贝泊汀α,不过仍有必要进一步研究,尤其是关于最佳给药剂量方面。正在积极研究替代给药方案,例如从开始治疗起每2周一次80,000U的促红细胞生成素α,或开始治疗后每3周一次80,000U并每周给药一次,以及开始治疗后每3周一次4.5 μg/kg并每周给药一次的达贝泊汀α,目标是为患者和医疗服务提供者增加灵活性。淋巴系统恶性肿瘤患者贫血的治疗是整体疾病管理的重要组成部分,对现有促红细胞生成素药物和新药物的持续研究就证明了这一点。尽管诸如美国国立综合癌症网络(NCCN)和美国血液学会(ASH)/美国临床肿瘤学会(ASCO)等组织发布的治疗指南建议,当Hb降至10 - 11 g/dL以下或基于临床症状时采用促红细胞生成素疗法进行干预,但数据表明贫血在很大程度上未得到充分认识和治疗。显然,有必要对淋巴系统恶性肿瘤患者贫血的定义、识别和最佳管理进行更新。

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