Megalakaki C
Department of Hematology, Metaxa Cancer Hospital, Piraeus, Greece.
J BUON. 2008 Jan-Mar;13(1):7-16.
During the last decade, anemia, a very common situation in patients with malignant diseases, either associated with chemotherapy or not, is being treated with recombinant erythropoietin (rEPO). Recent experimental findings have elucidated the role of EPO as a strongly anti-apoptotic agent in multiple non-erythroid and neoplastic tissues. The discovery of probably functional EPO receptors (EPOR) on malignant cells, hinting that EPO may act as a tumor growth factor, raised embarrassing thoughts regarding the routine administration of erythropoiesis-stimulating agents (ESAs). In addition, the results of a few clinical trials showing a negative impact on overall survival of rEPO-treated cancer patients, although strongly criticized for several methodological pitfalls, led the FDA to force a "black label" warning concerning the use of rEPO and to recommend that physicians should use the lowest possible dose of ESAs in chemotherapy-treated cancer patients. This recommendation comes in accord with the recent guidelines of European Organisation for Research and Treatment of Cancer (EORTC) which are reviewed in this paper, along with the structure of EPO and EPOR, the role of EPO on normal and malignant cells and the clinical applications of EPO.
在过去十年中，贫血在恶性疾病患者中非常常见，无论是否与化疗相关，都采用重组促红细胞生成素（rEPO）进行治疗。最近的实验结果阐明了促红细胞生成素（EPO）在多种非红细胞和肿瘤组织中作为一种强抗凋亡剂的作用。在恶性细胞上发现可能具有功能的EPO受体（EPOR），这暗示EPO可能作为一种肿瘤生长因子，引发了关于促红细胞生成素刺激剂（ESAs）常规给药的尴尬想法。此外，一些临床试验结果显示，rEPO治疗的癌症患者的总生存期受到负面影响，尽管因几个方法学缺陷而受到强烈批评，但这导致美国食品药品监督管理局（FDA）强制发布关于使用rEPO的“黑框”警告，并建议医生在化疗治疗的癌症患者中应使用尽可能低剂量的ESAs。这一建议与欧洲癌症研究与治疗组织（EORTC）最近的指南一致，本文将对该指南进行综述，同时还将介绍EPO和EPOR的结构、EPO对正常细胞和恶性细胞的作用以及EPO的临床应用。
