Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial
Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial
复制标题
DOI：
10.1093/jnci/djv248
复制
发表时间：
2015-11-01
影响因子：
10.3
通讯作者：
Wolmark, Norman
中科院分区：
文献类型：
--
作者：
Allegra, Carmen J.;Yothers, Greg;Wolmark, Norman
背景资料：国家外科辅助乳腺和肠道项目R-04旨在确定口服氟嘧啶卡培他滨是否可以在II/III期直肠癌的新辅助放射治疗期间替代连续输注5-FU，以及奥沙利铂的加入是否可以进一步增强氟嘧啶敏化放射的活性。接受术前放疗的临床II期或III期直肠癌患者被随机分配至2x2设计的四种化疗方案之一：CVI 5-FU或口服卡培他滨联合或不联合奥沙利铂。主要终点是局部区域肿瘤控制。使用Kaplan-Meier方法估计至事件发生时间终点分布。根据考克斯比例风险模型估计风险比。结果：在1608例随机化患者中，5-FU与卡培他滨方案在3年局部区域肿瘤事件发生率方面无统计学显著差异（11.2% vs 11.8%），5年DFS（66.4% vs 67.7%），或5年OS（79.9%对80.8%）;或奥沙利铂vs无奥沙利铂的局部-区域事件、DFS和OS三个终点（11.2% vs 12.1%，69.2% vs 64.2%，81.3% vs 79.0%）。奥沙利铂的添加与统计学显著更多的总体和3-4级腹泻相关（P < .0001）。三年的局部区域复发率在接受R 0切除术的患者范围从3.1%到5.1%，取决于研究arm.Conclusions：连续输注5-FU产生的局部区域控制，DFS和OS的结果与口服卡培他滨联合放疗获得的结果相似。本研究确立了卡培他滨作为直肠手术前的标准治疗。奥沙利铂未改善任何患者风险组的局部区域失败率、DFS或OS，但增加了相当大的毒性。
Background: National Surgical Adjuvant Breast and Bowel Project R-04 was designed to determine whether the oral fluoropyrimidine capecitabine could be substituted for continuous infusion 5-FU in the curative setting of stage II/III rectal cancer during neoadjuvant radiation therapy and whether the addition of oxaliplatin could further enhance the activity of fluoropyrimidine-sensitized radiation.Methods: Patients with clinical stage II or III rectal cancer undergoing preoperative radiation were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU or oral capecitabine with or without oxaliplatin. The primary endpoint was local-regional tumor control. Time-to-event endpoint distributions were estimated using the Kaplan-Meier method. Hazard ratios were estimated from Cox proportional hazard models. All statistical tests were two-sided.Results: Among 1608 randomized patients there were no statistically significant differences between regimens using 5-FU vs capecitabine in three-year local-regional tumor event rates (11.2% vs 11.8%), 5-year DFS (66.4% vs 67.7%), or 5-year OS (79.9% vs 80.8%); or for oxaliplatin vs no oxaliplatin for the three endpoints of local-regional events, DFS, and OS (11.2% vs 12.1%, 69.2% vs 64.2%, and 81.3% vs 79.0%). The addition of oxaliplatin was associated with statistically significantly more overall and grade 3-4 diarrhea (P < .0001). Three-year rates of local-regional recurrence among patients who underwent R0 resection ranged from 3.1 to 5.1% depending on the study arm.Conclusions: Continuous infusion 5-FU produced outcomes for local-regional control, DFS, and OS similar to those obtained with oral capecitabine combined with radiation. This study establishes capecitabine as a standard of care in the pre-operative rectal setting. Oxaliplatin did not improve the local-regional failure rate, DFS, or OS for any patient risk group but did add considerable toxicity.