Henry D H, Abels R I
Graduate Hospital, Philadelphia, PA 19146.
Semin Oncol. 1994 Apr;21(2 Suppl 3):21-8.
Anemia associated with advanced cancer is common. Contributing factors include the anemia of chronic disease, chemotherapy, radiation therapy, and bone marrow invasion with tumor. Based on the observation that endogenous erythropoietin (EPO) levels in anemic patients with cancer are inadequate for the degree of anemia, three randomized double-blind, placebo-controlled trials of recombinant human erythropoietin (rHuEPO) treatment in anemic patients with cancer were performed in patients (1) not receiving concomitant chemotherapy (NO CTX), (2) receiving myelosuppressive chemotherapy that did not include cisplatin (CTX-NO PLAT), and (3) receiving myelosuppressive cisplatin-containing chemotherapy (CTX-PLAT). In the NO CTX trial, patients were treated with rHuEPO 100 U/kg or placebo subcutaneously (SQ) three times per week for up to 8 weeks. In the CTX trials, patients were treated with rHuEPO 150 U/kg or placebo SQ three times per week for 12 weeks. Four hundred thirteen patients were enrolled (124, NO CTX; 157, CTX-NO PLAT; and 132, CTX-PLAT). In all three trials, patients receiving rHuEPO had a significantly (P < .004) greater increase in hematocrit (HCT) than placebo-treated patients. In the two CTX trials combined, rHuEPO-treated patients also had a significantly (P < or = .009) lower transfusion requirement than placebo-treated patients after the first month of therapy. Quality of life improved significantly (P < .05) in responding (> or = 6%-point HCT increase without transfusion) rHuEPO-treated patients compared with placebo-treated patients. Overall, no adverse events occurred more frequently in rHuEPO-treated patients compared with placebo-treated patients. Following completion of the double-blind phase, patients received rHuEPO on an open-label basis as needed for correction of anemia with the dose titrated to a maximum of 900 U/kg/wk. During total rHuEPO exposure (either started at the beginning of double-blind therapy for patients initially randomized to rHuEPO or at the beginning of open-label therapy for patients initially randomized to placebo; 363 treated/347 evaluable for efficacy), 40.0%, 56.1%, and 58.3% of the NO-CTX, CTX-NO PLAT, and CTX-PLAT patients, respectively, responded to rHuEPO therapy with an increase of HCT > or = 6% unrelated to transfusion.(ABSTRACT TRUNCATED AT 400 WORDS)
与晚期癌症相关的贫血很常见。促成因素包括慢性病贫血、化疗、放疗以及肿瘤侵犯骨髓。基于对癌症贫血患者内源性促红细胞生成素（EPO）水平不足以应对贫血程度的观察，对三组癌症贫血患者进行了三项随机双盲、安慰剂对照的重组人促红细胞生成素（rHuEPO）治疗试验，患者分别为：（1）未接受同步化疗（无CTX组）；（2）接受不含顺铂的骨髓抑制性化疗（CTX - 无铂组）；（3）接受含顺铂的骨髓抑制性化疗（CTX - 铂组）。在无CTX试验中，患者皮下注射（SQ）rHuEPO 100 U/kg或安慰剂，每周3次，共8周。在CTX试验中，患者皮下注射rHuEPO 150 U/kg或安慰剂，每周3次，共12周。共纳入413例患者（124例，无CTX组；157例，CTX - 无铂组；132例，CTX - 铂组）。在所有三项试验中，接受rHuEPO治疗的患者血细胞比容（HCT）的升高幅度显著（P <.004）大于接受安慰剂治疗的患者。在两项CTX试验合并分析中，接受rHuEPO治疗的患者在治疗第一个月后输血需求也显著（P ≤.009）低于接受安慰剂治疗的患者。与接受安慰剂治疗的患者相比，有反应（HCT升高≥6%且未输血）的接受rHuEPO治疗的患者生活质量显著改善（P <.05）。总体而言，与接受安慰剂治疗的患者相比，接受rHuEPO治疗的患者不良事件发生频率并未更高。双盲阶段结束后，患者根据需要接受开放标签的rHuEPO治疗以纠正贫血，剂量滴定至最大900 U/kg/周。在整个rHuEPO治疗期间（对于最初随机分配接受rHuEPO的患者从双盲治疗开始时起，对于最初随机分配接受安慰剂的患者从开放标签治疗开始时起；363例接受治疗/347例可评估疗效），无CTX组、CTX - 无铂组和CTX - 铂组分别有40.0%、56.1%和58.3%的患者对rHuEPO治疗有反应，HCT升高≥6%且与输血无关。（摘要截选至400字）
