Hershman Dawn L, Buono Donna L, Malin Jennifer, McBride Russell, Tsai Wei Yann, Neugut Alfred I
Columbia University Medical Center, 161 Fort Washington Ave, 10-1068, New York, NY 10032, USA.
J Natl Cancer Inst. 2009 Dec 2;101(23):1633-41. doi: 10.1093/jnci/djp387. Epub 2009 Nov 10.
Erythropoiesis-stimulating agents (erythropoietin and darbepoietin) have been approved to reduce the number of blood transfusions required during chemotherapy; however, concerns about the risks of venous thromboembolism and mortality exist.
We identified patients who were aged 65 years or older in the Surveillance, Epidemiology, and End Results-Medicare database; who were diagnosed with colon, non-small cell lung, or breast cancer or with diffuse large B-cell lymphoma from January 1, 1991, through December 31, 2002; and who received chemotherapy. The main outcome measures were claims for use of an erythropoiesis-stimulating agent, blood transfusion, venous thromboembolism (ie, deep vein thrombosis or pulmonary embolism), and overall survival. We used multivariable logistic regression models to analyze the association of erythropoiesis-stimulating agent use with clinical and demographic variables. We used time-dependent Cox proportional hazards models to analyze the association of time to receipt of first erythropoiesis-stimulating agent with venous thromboembolism and overall survival. All statistical tests were two-sided.
Among 56,210 patients treated with chemotherapy from 1991 through 2002, 15,346 (27%) received an erythropoiesis-stimulating agent. The proportion of patients receiving erythropoiesis-stimulating agents increased from 4.8% in 1991 to 45.9% in 2002 (P < .001). Use was associated with more recent diagnosis, younger age, urban residence, comorbidities, receipt of radiation therapy, female sex, and metastatic or recurrent cancer. The rate of blood transfusion per year during 1991-2002 remained constant at 22%. Venous thromboembolism developed in 1796 (14.3%) of the 12,522 patients who received erythropoiesis-stimulating agent and 3400 (9.8%) of the 34,820 patients who did not (hazard ratio = 1.93, 95% confidence interval = 1.79 to 2.07). Overall survival was similar in both groups.
Use of erythropoiesis-stimulating agent increased rapidly after its approval in 1991, but the blood transfusion rate did not change. Use of erythropoiesis-stimulating agents was associated with an increased risk of venous thromboembolism but not of mortality.
促红细胞生成素（促红细胞生成素和达比加群酯）已被批准用于减少化疗期间所需的输血次数；然而，人们对静脉血栓栓塞和死亡风险存在担忧。
我们在监测、流行病学和最终结果-医疗保险数据库中确定了年龄在65岁及以上的患者；这些患者在1991年1月1日至2002年12月31日期间被诊断患有结肠癌、非小细胞肺癌或乳腺癌或弥漫性大B细胞淋巴瘤；并且接受了化疗。主要结局指标是使用促红细胞生成素、输血、静脉血栓栓塞（即深静脉血栓形成或肺栓塞）和总生存期的索赔。我们使用多变量逻辑回归模型分析促红细胞生成素使用与临床和人口统计学变量之间的关联。我们使用时间依赖性Cox比例风险模型分析首次使用促红细胞生成素的时间与静脉血栓栓塞和总生存期之间的关联。所有统计检验均为双侧检验。
在1991年至2002年接受化疗的56210例患者中，15346例（27%）接受了促红细胞生成素。接受促红细胞生成素的患者比例从1991年的4.8%增加到2002年的45.9%（P <.001）。使用与更近的诊断、更年轻的年龄、城市居住、合并症、接受放射治疗时诊断、女性性别以及转移性或复发性癌症相关。1991 - 2002年期间每年的输血率保持在22%不变。在接受促红细胞生成素的12522例患者中，1796例（14.3%）发生了静脉血栓栓塞，在未接受促红细胞生成素的34820例患者中，3400例（9.8%）发生了静脉血栓栓塞（风险比 = 1.93，95%置信区间 = 1.79至2.07）。两组的总生存期相似。
促红细胞生成素在1991年获批后使用迅速增加，但输血率没有变化。使用促红细胞生成素与静脉血栓栓塞风险增加相关，但与死亡率无关。
