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重组人促红细胞生成素治疗实体瘤患者癌症相关或化疗所致贫血

Recombinant human erythropoietin in the treatment of cancer-related or chemotherapy-induced anaemia in patients with solid tumours.

作者信息

Nowrousian M R

机构信息

Department of Internal Medicine (Cancer Research), West Germany Cancer Center, University of Essen, Medical School, Germany.

出版信息

Med Oncol. 1998 Aug;15 Suppl 1:S19-28.

PMID:9785333
Abstract

Patients with cancer frequently develop anaemia, due either to the malignant disease itself or to its treatment. Various factors, including the type of malignancy and the type and intensity of chemotherapy, influence the prevalence of anaemia and the need for transfusions. Among patients with solid tumours, those with lung cancer and ovarian cancer are reported to have the highest frequency of anaemia (52% and 51%, respectively) and the highest rate of transfusion requirements (28% and 25%, respectively). Patients with a low level of haemoglobin (Hb) (10-12 g/dl) at the start of chemotherapy are particularly at risk of developing anaemia and requiring transfusions. Similarly, patients treated with platinum-based regimens more often develop anaemia and need transfusions. The frequency of transfusion requirements in these patients can amount to 47%-100%, depending on the cumulative dose of platinum and other risk factors, such as advanced age, loss of body weight before treatment, advanced disease stage, and particularly a low primary level of Hb (11 g/dl) and a decrease in Hb level (1-2 g/dl) after the first cycle of treatment. The causative mechanism of platinum-induced anaemia is reported to be, beside myelosuppression, a deficient production of erythropoietin (EPO) resulting from drug-induced renal tubular damage. In a number of randomised and nonrandomised studies, recombinant human (rh) EPO has been shown to be effective in the treatment of cancer-related anaemia (CRA) and in the prevention and treatment of chemotherapy-induced anaemia. An appropriate dose of rhEPO for the start of treatment is 150 U/kg given subcutaneously three times per week (t.i.w.). The response rate of anaemia ranges from 40% to 85%. rhEPO is well tolerated, but the cost of treatment requires patient selection and parameters predicting response as early as possible after the start of treatment. Appropriate groups of patients for treatment with rhEPO are those with an Hb level of < 10 g/dl and those with a higher Hb level, but symptomatic anaemia. Other groups are patients who are going to receive chemotherapy and have a low primary level of Hb (10-12 g/dl) and patients who receive platinum-based chemotherapy and have experienced a marked decrease in their Hb level (1-2 g/dl) from baseline to the second cycle of treatment. These patients have a high risk of becoming anaemic and requiring transfusions during chemotherapy. In anaemic cancer patients treated with rhEPO, an early indicator of response is an increase in Hb level of at least 0.5 g/dl in patients not receiving chemotherapy and 1 g/dl in those receiving chemotherapy, combined with an increase in reticulocyte count of at least 40,000 cells/microliter after 2 weeks of treatment in the first group of patients and after 4 weeks in the second.

摘要

癌症患者经常会出现贫血,这要么是由于恶性疾病本身,要么是由于其治疗所致。包括恶性肿瘤类型以及化疗类型和强度在内的各种因素,都会影响贫血的患病率和输血需求。在实体瘤患者中,据报道肺癌和卵巢癌患者的贫血发生率最高(分别为52%和51%),输血需求率也最高(分别为28%和25%)。化疗开始时血红蛋白(Hb)水平较低(10 - 12 g/dl)的患者尤其有发生贫血和需要输血的风险。同样,接受铂类方案治疗的患者更常出现贫血并需要输血。这些患者的输血需求频率可达47% - 100%,这取决于铂的累积剂量以及其他风险因素,如高龄、治疗前体重减轻、疾病晚期,尤其是初始Hb水平较低(<11 g/dl)以及第一个治疗周期后Hb水平下降(1 - 2 g/dl)。据报道,除骨髓抑制外,铂诱导贫血的致病机制是药物引起的肾小管损伤导致促红细胞生成素(EPO)生成不足。在一些随机和非随机研究中,重组人(rh)EPO已被证明可有效治疗癌症相关贫血(CRA)以及预防和治疗化疗引起的贫血。治疗开始时rhEPO的合适剂量是150 U/kg,皮下注射,每周三次(t.i.w.)。贫血的缓解率在40%至85%之间。rhEPO耐受性良好,但治疗费用需要在治疗开始后尽早进行患者选择和预测反应的参数评估。适合用rhEPO治疗的患者群体是Hb水平<10 g/dl的患者以及Hb水平较高但有症状性贫血的患者。其他群体是即将接受化疗且初始Hb水平较低(10 - 12 g/dl)的患者,以及接受铂类化疗且从基线到第二个治疗周期Hb水平有显著下降(1 - 2 g/dl)的患者。这些患者在化疗期间有很高的发生贫血和需要输血的风险。在用rhEPO治疗的贫血癌症患者中,反应的早期指标是未接受化疗的患者Hb水平至少升高0.5 g/dl,接受化疗的患者Hb水平至少升高1 g/dl,并且第一组患者治疗2周后、第二组患者治疗4周后网织红细胞计数至少增加40,000个/微升。

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