辅助性自体肾肿瘤细胞疫苗与根治性肾切除术后肾细胞癌患者肿瘤进展风险：III期随机对照试验

Adjuvant autologous renal tumour cell vaccine and risk of tumour progression in patients with renal-cell carcinoma after radical nephrectomy: phase III, randomised controlled trial.

作者信息

Jocham Dieter, Richter Axel, Hoffmann Lothar, Iwig Klaus, Fahlenkamp Dirk, Zakrzewski Günther, Schmitt Eberhard, Dannenberg Thomas, Lehmacher Walter, von Wietersheim Jörn, Doehn Christian

机构信息

Department of Urology, University of Lübeck Medical School, Ratzeburger Allee 160, 23538 Lübeck, Germany.

出版信息

Lancet. 2004 Feb 21;363(9409):594-9. doi: 10.1016/S0140-6736(04)15590-6.

DOI:10.1016/S0140-6736(04)15590-6

PMID:14987883

Abstract

BACKGROUND

Organ-confined renal-cell carcinoma is associated with tumour progression in up to 50% of patients after radical nephrectomy. At present, no effective adjuvant treatment is established. We aimed to investigate the effect of an autologous renal tumour cell vaccine on risk of tumour progression in patients with stage pT2-3b pN0-3 M0 renal-cell carcinoma.

METHODS

Between January, 1997, and September, 1998, 558 patients with a renal tumour scheduled for radical nephrectomy were enrolled at 55 institutions in Germany. Before surgery, all patients were centrally randomised to receive autologous renal tumour cell vaccine (six intradermal applications at 4-week intervals postoperatively; vaccine group) or no adjuvant treatment (control group). The primary endpoint of the trial was to reduce the risk of tumour progression, defined as progression or death. All patients were assessed after standardised diagnostic investigations at 6-month intervals for a minimum of 4.5 years.

FINDINGS

By preoperative and postoperative inclusion criteria, 379 patients were assessable for the intention-to-treat analysis. At 5-year and 70-month follow-up, the hazard ratios for tumour progression were 1.58 (95% CI 1.05-2.37) and 1.59 (1.07-2.36), respectively, in favour of the vaccine group (p=0.0204, log-rank test). 5-year and 70-month progression-free survival rates were 77.4% and 72%, respectively, in the vaccine group and 67.8% and 59.3%, respectively, in the control group. The vaccine was well tolerated, with only 12 adverse events associated with the treatment.

INTERPRETATION

Adjuvant treatment with autologous renal tumour cell vaccine in patients with renal-cell carcinoma after radical nephrectomy seems to be beneficial and can be considered in patients undergoing radical nephrectomy due to organ-confined renal-cell carcinoma of more than 2.5 cm in diameter.

摘要

背景

局限性肾癌在根治性肾切除术后高达50%的患者中与肿瘤进展相关。目前，尚未确立有效的辅助治疗方法。我们旨在研究自体肾肿瘤细胞疫苗对pT2 - 3b pN0 - 3 M0期肾癌患者肿瘤进展风险的影响。

方法

1997年1月至1998年9月期间，德国55家机构招募了558例计划接受根治性肾切除术的肾肿瘤患者。术前，所有患者被集中随机分组，分别接受自体肾肿瘤细胞疫苗（术后每隔4周进行6次皮内注射；疫苗组）或不接受辅助治疗（对照组）。该试验的主要终点是降低肿瘤进展风险，定义为进展或死亡。所有患者在标准化诊断检查后每隔6个月进行评估，至少持续4.5年。

结果

根据术前和术后纳入标准，379例患者可用于意向性分析。在5年和70个月的随访中，疫苗组肿瘤进展的风险比分别为1.58（95%CI 1.05 - 2.37）和1.59（1.07 - 2.36），支持疫苗组（p = 0.0204，对数秩检验）。疫苗组5年和70个月的无进展生存率分别为77.4%和72%，对照组分别为67.8%和59.3%。该疫苗耐受性良好，仅12例不良事件与治疗相关。