Henke Michael, Mattern Dominik, Pepe Margaret, Bézay Christina, Weissenberger Christian, Werner Martin, Pajonk Frank
Klinik für Strahlenheilkunde, Universitätsklinikum, Robert Koch Strasse, 3 D-79106, Freiburg, Germany.
J Clin Oncol. 2006 Oct 10;24(29):4708-13. doi: 10.1200/JCO.2006.06.2737.
Recent reports suggest that cancer control may worsen if erythropoietin is administered. We investigated whether erythropoietin receptor expression on cancer cells may correlate with this unexpected finding.
Cancer tissue from patients with advanced carcinoma of the head and neck (T3, T4, or nodal involvement) and scheduled for radiotherapy was assayed retrospectively for erythropoietin receptor expression by immunohistochemistry. Patients were anemic and randomized to receive epoetin beta (300 U/kg) or placebo under double-blind conditions, given three times weekly starting 10 to 14 days before and continuing throughout radiotherapy. We administered 60 Gy following complete resection or 64 Gy subsequent to microscopically incomplete resection; 70 Gy were given following macroscopically incomplete resection or for definitive radiotherapy alone. We determined if the effect of epoetin beta on locoregional progression-free survival was correlated with the expression of erythropoietin receptors on cancer cells using a Cox proportional hazards regression model.
We studied 154 of 157 randomly assigned patients; 104 samples were positive, and 50 were negative for receptor expression. Locoregional progression-free survival was substantially poorer if epoetin beta was administered to patients positive for receptor expression compared with placebo (adjusted relative risk, 2.07; 95% CI, 1.27 to 3.36; P < .01). In contrast, epoetin beta did not impair outcome in receptor-negative patients (adjusted relative risk, 0.94; 95% CI, 0.47 to 1.90; P = .86). The difference in treatment associated relative risks (2.07 v 0.94) was borderline statistically significant (P = .08).
Erythropoietin might adversely affect prognosis of head and neck cancer patients if cancer cells express erythropoietin receptors.
近期报告提示，使用促红细胞生成素可能会使癌症控制情况恶化。我们研究了癌细胞上促红细胞生成素受体的表达是否与这一意外发现相关。
对计划接受放疗的晚期头颈癌（T3、T4或有淋巴结转移）患者的癌组织进行回顾性分析，采用免疫组织化学法检测促红细胞生成素受体的表达。患者均为贫血患者，在双盲条件下随机接受β-促红细胞生成素（300 U/kg）或安慰剂治疗，每周给药3次，从放疗前10至14天开始，持续至整个放疗过程。在完全切除后给予60 Gy放疗，或在显微镜下切除不完全后给予64 Gy放疗；在肉眼切除不完全或仅进行根治性放疗后给予70 Gy放疗。我们使用Cox比例风险回归模型确定β-促红细胞生成素对局部区域无进展生存期的影响是否与癌细胞上促红细胞生成素受体的表达相关。
我们研究了157例随机分组患者中的154例；104个样本受体表达呈阳性，50个样本呈阴性。与安慰剂相比，对受体表达阳性的患者给予β-促红细胞生成素时，局部区域无进展生存期明显较差（调整后的相对风险为2.07；95%可信区间为1.27至3.36；P < 0.01）。相比之下，β-促红细胞生成素对受体阴性的患者的预后没有损害（调整后的相对风险为0.94；95%可信区间为0.47至1.90；P = 0.86）。治疗相关相对风险的差异（2.07比0.94）在统计学上接近显著（P = 0.08）。
如果癌细胞表达促红细胞生成素受体，促红细胞生成素可能会对头颈癌患者的预后产生不利影响。
