结直肠癌转移灶潜在根治性切除术后的辅助化疗：两项随机试验的汇总分析

Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials.

作者信息

Mitry Emmanuel, Fields Anthony L A, Bleiberg Harry, Labianca Roberto, Portier Guillaume, Tu Dongsheng, Nitti Donato, Torri Valter, Elias Dominique, O'Callaghan Chris, Langer Bernard, Martignoni Giancarlo, Bouché Olivier, Lazorthes Franck, Van Cutsem Eric, Bedenne Laurent, Moore Malcolm J, Rougier Philippe

机构信息

Hépato-Gastroentérologie et Oncologie Digestive, Hôpital Ambroise Paré, Boulogne, France.

出版信息

J Clin Oncol. 2008 Oct 20;26(30):4906-11. doi: 10.1200/JCO.2008.17.3781. Epub 2008 Sep 15.

DOI:10.1200/JCO.2008.17.3781

PMID:18794541

Abstract

PURPOSE

Adjuvant systemic chemotherapy administered after surgical resection of colorectal cancer metastases may reduce the risk of recurrence and improve survival, but its benefit has never been demonstrated. Two phase III trials (Fédération Francophone de Cancérologie Digestive [FFCD] Trial 9002 and the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Clinical Trials Group/Gruppo Italiano di Valutazione Interventi in Oncologia [ENG] trial) used a similar design and showed a trend favoring adjuvant chemotherapy, but both had to close prematurely because of slow accrual, thus lacking the statistical power to demonstrate the predefined difference in survival. We report here a pooled analysis based on individual data from these two trials.

PATIENTS AND METHODS

After complete resection of colorectal liver or lung metastases, patients were randomly assigned to chemotherapy (CT arm; fluorouracil [FU] 400 mg/m(2) administered intravenously [IV] once daily plus dl-leucovorin 200 mg/m(2) [FFCD] x 5 days or FU 370 mg/m(2) plus l-leucovorin 100 mg/m(2) IV x 5 days [ENG] for six cycles at 28-day intervals) or to surgery alone (S arm).

RESULTS

A total of 278 patients (CT, n = 138; S, n = 140) were included in the pooled analysis. Median progression-free survival was 27.9 months in the CT arm as compared with 18.8 months in the S arm (hazard ratio = 1.32; 95% CI, 1.00 to 1.76; P = .058). Median overall survival was 62.2 months in the CT arm compared with 47.3 months in the S arm (hazard ratio = 1.32; 95% CI, 0.95 to 1.82; P = .095). Adjuvant chemotherapy was independently associated with both progression-free survival and overall survival in multivariable analysis.

CONCLUSION

This pooled analysis shows a marginal statistical significance in favor of adjuvant chemotherapy with an FU bolus-based regimen after complete resection of colorectal cancer metastases.

摘要

目的

在结直肠癌转移灶手术切除后给予辅助性全身化疗可能会降低复发风险并提高生存率，但其益处尚未得到证实。两项III期试验（法语国家消化肿瘤联合会[FFCD]试验9002以及欧洲癌症研究与治疗组织/加拿大国家癌症研究所临床试验组/意大利肿瘤治疗评估小组[ENG]试验）采用了相似的设计，显示出辅助化疗有益的趋势，但两项试验均因入组缓慢而不得不提前结束，因此缺乏统计学效力来证明预设的生存差异。我们在此报告基于这两项试验个体数据的汇总分析。

患者与方法

在结直肠癌肝或肺转移灶完全切除后，患者被随机分配至化疗组（CT组；氟尿嘧啶[FU]400mg/m²静脉注射[IV]每日1次加亚叶酸钙200mg/m²[FFCD]共5天，或FU 370mg/m²加亚叶酸钙100mg/m²静脉注射共5天[ENG]，每28天为1周期，共6个周期）或单纯手术组（S组）。

结果

汇总分析共纳入278例患者（CT组，n = 138；S组，n = 140）。CT组的无进展生存期（PFS）中位数为27.9个月，而S组为18.8个月（风险比 = 1.32；95%置信区间[CI]，1.00至1.76；P = 0.058）。CT组的总生存期（OS）中位数为62.2个月，而S组为47.3个月（风险比 = 1.32；95%CI，0.95至1.82；P = 0.095）。在多变量分析中，辅助化疗与无进展生存期和总生存期均独立相关。