结肠癌辅助治疗的随机试验：NSABP C-01方案的10年结果

Randomized trial of adjuvant therapy in colon carcinoma: 10-year results of NSABP protocol C-01.

作者信息

Smith Roy E, Colangelo Linda, Wieand H Samuel, Begovic Mirsada, Wolmark Norman

机构信息

NSABP Operations Center, Pittsburgh, PA (RES, NM); NSABP Biostatistical Center, Pittsburgh, PA 15212-5234, USA.

出版信息

J Natl Cancer Inst. 2004 Aug 4;96(15):1128-32. doi: 10.1093/jnci/djh220.

DOI:10.1093/jnci/djh220

PMID:15292384

Abstract

BACKGROUND

The National Surgical Adjuvant Breast and Bowel Project C-01 trial reported in 1988 that, for patients with adenocarcinoma of the colon, compared with surgery alone, 1) postoperative chemotherapy with 1-(2-chloroethyl)-3-(4-trans-methylcyclohexyl)-1-nitrosourea (i.e., MeCCNU or semustine), vincristine, and 5-fluorouracil was associated with better 5-year disease-free and overall survival and 2) postoperative immunotherapy with bacillus Calmette-Guérin was associated with better 5-year overall, but not disease-free, survival. We now provide a 10-year update of this trial.

METHODS

Between November 11, 1977, and February 28, 1983, 1166 patients with resected Dukes' stage B and C adenocarcinoma of the colon were stratified by Dukes' stage, sex, and age (<65 years or > or =65 years) and then randomly assigned to receive no further treatment (surgery alone; 394 patients), adjuvant chemotherapy (379 patients), or adjuvant immunotherapy (393 patients). Those eligible for follow-up included 375 (95.2%) patients in the surgery-alone group, 349 (92.1%) patients in the adjuvant-chemotherapy group, and 372 (94.7%) patients in the adjuvant-immunotherapy group. All statistical tests were two-sided.

RESULTS

No difference was observed between patients in the chemotherapy group and those in the surgery-alone group in 10-year disease-free survival (hazard ratio [HR] = 1.14, 95% confidence interval [CI] = 0.94 to 1.39;P =.17) or overall survival (HR = 1.12, 95% CI = 0.91 to 1.38; P=.27). Immunotherapy did not appear to prevent tumor relapse after 10 years (for surgery alone versus immunotherapy, relative risk [RR] = 0.99, 95% CI = 0.78 to 1.25; P =.93) but had a beneficial effect on 10-year overall survival (for surgery alone versus immunotherapy, RR = 1.27, 95% CI = 1.03 to 1.56; P =.02) that apparently results from a reduction in deaths associated with comorbidities in the immunotherapy group.

CONCLUSION

The disease-free and overall survival benefit associated with chemotherapy in this patient population is of limited duration, disappearing after 10 years.

摘要

背景

1988年公布的国家外科辅助乳腺和肠道项目C-01试验报告称，对于结肠癌患者，与单纯手术相比，1）术后使用1-（2-氯乙基）-3-（4-反式甲基环己基）-1-亚硝基脲（即甲基环己亚硝脲或司莫司汀）、长春新碱和5-氟尿嘧啶进行化疗与更好的5年无病生存率和总生存率相关，2）术后使用卡介苗进行免疫治疗与更好的5年总生存率相关，但与无病生存率无关。我们现在提供该试验的10年随访结果。

方法

在1977年11月11日至1983年2月28日期间，1166例切除的结肠癌Dukes B期和C期腺癌患者按Dukes分期、性别和年龄（<65岁或≥65岁）分层，然后随机分配接受进一步治疗（单纯手术；394例患者）、辅助化疗（379例患者）或辅助免疫治疗（393例患者）。符合随访条件的患者包括单纯手术组的375例（95.2%）、辅助化疗组的349例（92.1%）和辅助免疫治疗组的372例（94.7%）。所有统计检验均为双侧检验。

结果

化疗组患者与单纯手术组患者在10年无病生存率（风险比[HR]=1.14，95%置信区间[CI]=0.94至1.39；P=0.17）或总生存率（HR=1.12，95%CI=0.91至1.38；P=0.27）方面未观察到差异。免疫治疗在10年后似乎并未预防肿瘤复发（单纯手术与免疫治疗相比，相对风险[RR]=0.99，95%CI=0.78至1.25；P=0.93），但对10年总生存率有有益影响（单纯手术与免疫治疗相比，RR=1.27，95%CI=1.03至1.56；P=0.02），这显然是由于免疫治疗组中与合并症相关的死亡人数减少所致。