肾细胞癌肾切除术后高复发风险患者的辅助 5-氟尿嘧啶、α-干扰素和白细胞介素-2与观察治疗的比较：欧洲癌症研究与治疗组织（泌尿生殖系统癌症组）/国家癌症研究所的 III 期随机临床试验结果。

Adjuvant 5-flurouracil, alpha-interferon and interleukin-2 versus observation in patients at high risk of recurrence after nephrectomy for renal cell carcinoma: results of a phase III randomised European Organisation for Research and Treatment of Cancer (Genito-Urinary Cancers Group)/National Cancer Research Institute trial.

机构信息

The Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.

出版信息

Eur J Cancer. 2014 Jan;50(1):70-7. doi: 10.1016/j.ejca.2013.08.019. Epub 2013 Sep 25.

DOI:10.1016/j.ejca.2013.08.019

PMID:24074763

Abstract

BACKGROUND

The purpose of this trial was to compare adjuvant 5-flurouracil, alpha-interferon and interleukin-2 to observation in patients at high risk of recurrence after nephrectomy for renal cell carcinoma (RCC) in terms of disease free survival, overall survival and quality of life (QoL).

PATIENTS AND METHODS

Patients 8weeks post nephrectomy for RCC, without macroscopic residual disease, with stage T3b-c,T4 or any pT and pN1 or pN2 or positive microscopic margins or microscopic vascular invasion, and no metastases were randomised to receive adjuvant treatment or observation. QoL was assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-30 (QLQC-30). Treatment delivery and toxicity were monitored. The trial was designed to detect an increase in 3year disease free survival (DFS) from 50% on observation to 65% on treatment (hazard ratio (HR)=0.63) with 90% power and two-sided alpha=0.05.

RESULTS

From 1998 to 2007, 309 patients were randomised (155 to observation; 154 to treatment). 35% did not complete the treatment, primarily due to toxicity (92% of patients experienced ⩾grade 2, 41% ⩾grade 3). Statistically significant differences between the arms in QoL parameters at 2months disappeared by 6months although there was suggestion of a persistent deficit in fatigue and physical function. Median follow-up was 7years (maximum 12.1years). 182 patients relapsed or died. DFS at 3years was 50% with observation and 61% with treatment (HR 0.84, 95% confidence interval (CI) 0.63-1.12, p=0.233). 124 patients died. Overall survival (OS) at 5years was 63% with observation and 70% with treatment (HR 0.87, 95% CI 0.61-1.23, p=0.428).

CONCLUSIONS

The treatment is associated with significant toxicity. There is no statistically significant benefit for the regimen in terms of disease free or overall survival.

摘要

背景

本试验旨在比较辅助应用 5-氟尿嘧啶、α-干扰素和白细胞介素-2与观察在肾细胞癌（RCC）肾切除术后有高复发风险的患者中的疗效，评价指标包括无病生存、总生存和生活质量（QoL）。

患者和方法

患者在肾切除术后 8 周，无肉眼残余疾病，分期为 T3b-c、T4 或任何 pT 和 pN1 或 pN2 或阳性显微镜下边缘或显微镜下血管侵犯，且无转移，随机接受辅助治疗或观察。采用欧洲癌症研究与治疗组织（EORTC）生活质量问卷-30（QLQC-30）评估 QoL。监测治疗的实施和毒性。该试验旨在检测无病生存（DFS）从观察组的 50%增加到治疗组的 65%（风险比（HR）=0.63），具有 90%的功效和双侧 α=0.05。

结果

1998 年至 2007 年，共纳入 309 名患者（观察组 155 例，治疗组 154 例）。35%的患者未完成治疗，主要是由于毒性（92%的患者发生 ⩾2 级毒性，41% ⩾3 级毒性）。尽管疲劳和身体功能仍存在持续缺陷，但治疗组和观察组在治疗后 2 个月时 QoL 参数的差异消失。中位随访时间为 7 年（最长 12.1 年）。182 例患者复发或死亡。观察组 3 年 DFS 为 50%，治疗组为 61%（HR 0.84，95%CI 0.63-1.12，p=0.233）。124 例患者死亡。观察组 5 年 OS 为 63%，治疗组为 70%（HR 0.87，95%CI 0.61-1.23，p=0.428）。