干扰素 alfa-2a 与干扰素 alfa-2a、白细胞介素-2 和氟尿嘧啶联合治疗未经治疗的转移性肾细胞癌患者（MRC RE04/EORTC GU 30012）：一项开放标签随机试验。
Interferon alfa-2a versus combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil in patients with untreated metastatic renal cell carcinoma (MRC RE04/EORTC GU 30012): an open-label randomised trial.
机构信息
Royal Marsden Hospital NHS Trust, London, UK.
出版信息
Lancet. 2010 Feb 20;375(9715):641-8. doi: 10.1016/S0140-6736(09)61921-8. Epub 2010 Feb 10.
BACKGROUND
In metastatic renal cell carcinoma combinations of interferon alfa-2a, interleukin-2, and fluorouracil produce higher response rates and longer progression-free survival than do single agents. We aimed to compare overall survival in patients receiving combination treatment or interferon alfa-2a.
METHODS
RE04/30012 was an open-label randomised trial undertaken in 50 centres across eight countries. 1006 treatment-naive patients diagnosed with advanced metastatic renal cell carcinoma were randomly allocated (1 to 1) by minimisation to receive interferon alfa-2a alone or combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil. Treatment was not masked. The primary endpoint was overall survival. Treatment groups were compared with a non-stratified log-rank test. Analysis was by intention to treat. This study is registered, number ISRCTN 46518965.
FINDINGS
502 patients were randomly assigned to receive interferon alfa-2a and 504 to receive combined treatment. Median follow-up was 37.2 months (24.8-52.3). Median overall survival was 18.8 months (17.0-23.2) for patients receiving interferon alfa-2a versus 18.6 months (16.5-20.6) for those receiving combination therapy. Overall survival did not differ between the two groups (hazard ratio 1.05 [95% CI 0.90-1.21], p=0.55; absolute difference 0.3% (-5.1 to 5.6) at 1 year and 2.7% (-8.2 to 2.9) at 3 years). Serious adverse events were reported in 113 (23%) patients receiving interferon alfa-2a and 131 (26%) of those receiving combined treatment.
INTERPRETATION
Although combination therapy does not improve overall or progression-free survival compared with interferon alfa-2a alone, immunotherapy might still have a role because it can produce remissions that are of clinically relevant length in some patients. Identification of patients who will benefit from immunotherapy is crucial.
FUNDING
UK Medical Research Council.
背景
在转移性肾细胞癌中，与干扰素 alfa-2a、白细胞介素-2 和氟尿嘧啶联合使用比单一药物产生更高的反应率和更长的无进展生存期。我们旨在比较接受联合治疗或干扰素 alfa-2a 治疗的患者的总生存率。
方法
RE04/30012 是一项在八个国家的 50 个中心进行的开放性随机试验。1006 名未经治疗的晚期转移性肾细胞癌患者通过最小化随机分配（1:1）接受干扰素 alfa-2a 单药治疗或干扰素 alfa-2a、白细胞介素-2 和氟尿嘧啶联合治疗。治疗未设盲。主要终点是总生存期。治疗组与非分层对数秩检验进行比较。分析采用意向治疗。这项研究已注册，编号 ISRCTN 46518965。
结果
502 名患者被随机分配接受干扰素 alfa-2a 治疗，504 名患者接受联合治疗。中位随访时间为 37.2 个月（24.8-52.3）。接受干扰素 alfa-2a 治疗的患者中位总生存期为 18.8 个月（17.0-23.2），而接受联合治疗的患者为 18.6 个月（16.5-20.6）。两组总生存期无差异（风险比 1.05 [95%CI 0.90-1.21]，p=0.55；1 年时绝对差异为 0.3%（-5.1 至 5.6），3 年时为 2.7%（-8.2 至 2.9））。113 名（23%）接受干扰素 alfa-2a 治疗的患者和 131 名（26%）接受联合治疗的患者发生严重不良事件。
解释
尽管与干扰素 alfa-2a 单药治疗相比，联合治疗并未改善总生存期或无进展生存期，但免疫疗法可能仍有作用，因为它可以在一些患者中产生具有临床相关长度的缓解。确定将从免疫疗法中获益的患者至关重要。
资金
英国医学研究理事会。
Zotero 插件