Littlewood Timothy J, Nortier Johan, Rapoport Bernardo, Pawlicki Marek, de Wasch Gilbert, Vercammen Els, Schuette Wolfgang, Wils Jacques, Freund Mathias
John Radcliffe Hospital, Oxford, UK.
Hematol Oncol. 2003 Dec;21(4):169-80. doi: 10.1002/hon.722.
Anemia, a commonly occurring morbidity in patients with cancer, often leads to diminished quality of life (QOL). Numerous clinical trials have shown that epoetin alfa treatment improves hematologic and QOL variables in cancer patients. The clinical trial analysis reported here was performed to assess response to epoetin alfa in patients with hematologic malignancies. Cancer patients with anemia undergoing non-platinum-based chemotherapy who were enrolled in a multinational, randomized (2:1), double-blind, placebo-controlled trial were prospectively stratified by tumor type (hematologic, solid). Efficacy endpoints included proportion of patients transfused after day 28; change in hemoglobin (Hb) level from baseline to last assessment; proportion of treatment responders (increase in Hb > or =2 g/dl unrelated to transfusion) and correctors (patients whose Hb levels reached > or =12 g/dl during the study); and QOL. The protocol was amended before unblinding to prospectively collect and assess survival data 12 months after the last patient completed the study, and survival for the full study cohort was estimated using Kaplan-Meier techniques. Efficacy analyses of hematologic and QOL variables, as well as Kaplan-Meier estimates of survival, were performed post hoc for the hematologic tumor stratum. Among patients with hematologic malignancies, the mean increase in Hb levels was greater with epoetin alfa than with placebo treatment (2.2 vs. 0.3 g/dl). Transfusion requirements were lower in patients who received epoetin alfa versus placebo (25.2 vs. 43.1%), and the proportion of responders and correctors was higher with epoetin alfa than with placebo (75.2 vs. 16.7% and 72.6 vs. 14.8%, respectively). Patients who received epoetin alfa had improved QOL while patients who received placebo had decreased QOL. These results are similar to those seen in the full study cohort, where differences between epoetin alfa and placebo were significant (P<0.05) for all five primary cancer- and anemia-specific QOL domains evaluated. Although the study was not powered for survival, Kaplan-Meier estimates showed a trend in overall survival favoring epoetin alfa in both the full study cohort and the hematologic subgroup. Epoetin alfa treatment was well tolerated. Epoetin alfa therapy increased Hb levels, reduced transfusion requirements, and improved QOL in patients with anemia undergoing non-platinum chemotherapy for hematologic malignancies.
贫血是癌症患者中常见的一种病症，常常导致生活质量（QOL）下降。大量临床试验表明，促红细胞生成素α治疗可改善癌症患者的血液学指标和生活质量相关变量。此处报告的临床试验分析旨在评估血液系统恶性肿瘤患者对促红细胞生成素α的反应。参加一项多国、随机（2:1）、双盲、安慰剂对照试验的接受非铂类化疗的贫血癌症患者，按肿瘤类型（血液系统、实体瘤）进行前瞻性分层。疗效终点包括第28天之后接受输血的患者比例；从基线到最后一次评估时血红蛋白（Hb）水平的变化；治疗有反应者（Hb升高≥2 g/dl且与输血无关）和校正者（研究期间Hb水平达到≥12 g/dl的患者）的比例；以及生活质量。在揭盲前对方案进行了修订，以便前瞻性收集和评估最后一名患者完成研究12个月后的生存数据，并使用Kaplan-Meier技术估计整个研究队列的生存率。对血液学肿瘤亚组事后进行了血液学和生活质量相关变量的疗效分析以及Kaplan-Meier生存估计。在血液系统恶性肿瘤患者中，促红细胞生成素α组的Hb水平平均升高幅度大于安慰剂治疗组（2.2 vs. 0.3 g/dl）。接受促红细胞生成素α的患者输血需求低于接受安慰剂的患者（25.2% vs. 43.1%），促红细胞生成素α组的有反应者和校正者比例高于安慰剂组（分别为75.2% vs. 16.7%和72.6% vs. 14.8%）。接受促红细胞生成素α的患者生活质量得到改善，而接受安慰剂的患者生活质量下降。这些结果与整个研究队列中观察到的结果相似，在评估的所有五个主要癌症及贫血特异性生活质量领域中，促红细胞生成素α与安慰剂之间的差异均具有统计学意义（P<0.05）。尽管该研究未设定足够的样本量来评估生存情况，但Kaplan-Meier估计显示，在整个研究队列和血液学亚组中，总体生存均有倾向于促红细胞生成素α的趋势。促红细胞生成素α治疗耐受性良好。促红细胞生成素α治疗可提高接受非铂类化疗的血液系统恶性肿瘤贫血患者的Hb水平，降低输血需求，并改善其生活质量。
