Leyland-Jones Brian, Semiglazov Vladimir, Pawlicki Marek, Pienkowski Tadeusz, Tjulandin Sergei, Manikhas George, Makhson Antoly, Roth Anton, Dodwell David, Baselga Jose, Biakhov Mikhail, Valuckas Konstantinas, Voznyi Edouard, Liu Xiangyang, Vercammen Els
Department of Medical Oncology, McGill University, 546 Pine Avenue W, Montreal, Quebec, Canada H2W 1S6.
J Clin Oncol. 2005 Sep 1;23(25):5960-72. doi: 10.1200/JCO.2005.06.150. Epub 2005 Aug 8.
To evaluate the effect on survival and quality of life of maintaining hemoglobin (Hb) in the range of 12 to 14 g/dL with epoetin alfa versus placebo in women with metastatic breast cancer (MBC) receiving first-line chemotherapy.
Eligible patients were randomly assigned to receive epoetin alfa 40,000 U once weekly or placebo for 12 months. Study drug was initiated if baseline Hb was < or = 13 g/dL or when Hb decreased to < or = 13g/dL during the study. The primary end point was 12-month overall survival (OS).
The study drug administration was stopped early in accordance with a recommendation from the Independent Data Monitoring Committee because of higher mortality in the group treated with epoetin alfa. Enrollment had been completed, with 939 patients enrolled (epoetin alfa, n = 469; placebo, n = 470). Most patients had Hb more than 12 g/dL at baseline (median Hb, 12.8 g/dL) or during the study. From the final analysis, 12-month OS was 70% for epoetin alfa recipients and 76% for placebo recipients (P = .01). Optimal tumor response and time to disease progression were similar between groups. The reason for the difference in mortality between groups could not be determined from additional subsequent analyses involving both study data and chart review.
In this trial, the use of epoetin alfa to maintain high Hb targets in women with MBC, most of whom did not have anemia at the start of treatment, was associated with decreased survival. Additional research is required to clarify the potential impact of erythropoietic agents on survival when the Hb target range is 10 to 12 g/dL.
评估在接受一线化疗的转移性乳腺癌（MBC）女性患者中，使用促红细胞生成素α将血红蛋白（Hb）维持在12至14 g/dL范围内与使用安慰剂相比，对生存和生活质量的影响。
符合条件的患者被随机分配接受每周一次40,000 U促红细胞生成素α或安慰剂，持续12个月。如果基线Hb≤13 g/dL或在研究期间Hb降至≤13 g/dL，则开始使用研究药物。主要终点是12个月总生存期（OS）。
由于促红细胞生成素α治疗组死亡率较高，根据独立数据监测委员会的建议，研究药物的给药提前停止。入组已完成，共纳入939例患者（促红细胞生成素α组，n = 469；安慰剂组，n = 470）。大多数患者在基线时（Hb中位数为12.8 g/dL）或研究期间Hb超过12 g/dL。最终分析显示，促红细胞生成素α接受者的12个月OS为70%，安慰剂接受者为76%（P = 0.01）。两组间最佳肿瘤反应和疾病进展时间相似。无法通过涉及研究数据和病历审查的后续额外分析确定两组间死亡率差异的原因。
在本试验中，对于大多数在治疗开始时没有贫血的MBC女性患者，使用促红细胞生成素α维持高Hb目标与生存率降低相关。当Hb目标范围为10至12 g/dL时，需要进一步研究以阐明促红细胞生成剂对生存的潜在影响。
