Modified FOLFOX6 With or Without Radiation Versus Fluorouracil and Leucovorin With Radiation in Neoadjuvant Treatment of Locally Advanced Rectal Cancer: Initial Results of the Chinese FOWARC Multicenter, Open-Label, Randomized Three-Arm Phase III Trial
Modified FOLFOX6 With or Without Radiation Versus Fluorouracil and Leucovorin With Radiation in Neoadjuvant Treatment of Locally Advanced Rectal Cancer: Initial Results of the Chinese FOWARC Multicenter, Open-Label, Randomized Three-Arm Phase III Trial
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改良 FOLFOX6 联合或不联合放射与氟尿嘧啶和亚叶酸联合放射治疗局部晚期直肠癌的新辅助治疗：中国 FOWARC 多中心、开放标签、随机三臂 III 期试验的初步结果
DOI：
10.1200/jco.2016.66.6198
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发表时间：
2016-09-20
影响因子：
45.3
通讯作者：
Wang, Jianping
中科院分区：
文献类型：
--
作者：
Deng, Yanhong;Chi, Pan;Wang, Jianping
目的全直肠系膜切除联合以氟尿嘧啶为基础的术前放化疗和术后化疗是局部晚期直肠癌的标准治疗方法。本研究调查了在术前放疗和不放疗的情况下添加奥沙利铂的情况。 方法在这项多中心、开放标签的 III 期试验中，我们将患有局部晚期 II/III 期直肠癌的中国成年人（18 至 75 岁）随机分配（1:1:1）接受三种治疗：5 个周期为 2 周的氟尿嘧啶输注周期（甲酰四氢叶酸 400 mg/m(2)、氟尿嘧啶 400 mg/m(2) 和氟尿嘧啶 2.4 g/m(2) 持续 48 小时）加放疗（46.0 至 50.4 Gy，在第 2 至 4 个周期期间分 23 至 25 次给药），然后进行手术和 7 个周期的氟尿嘧啶输注，同样的治疗加上每个周期第 1 天静脉注射奥沙利铂 85 mg/m(2)（改良 FOLFOX6 [mFOLFOX6]），或 4 至 6 个周期mFOLFOX6 后进行手术和六到八个周期的 mFOLFOX6。使用计算机生成的区块随机化代码进行随机分配。主要终点是 3 年无病生存率。报告了组织病理学反应和毒性的次要终点。结果2010年6月至2015年2月期间总共入组了495名患者； 475 例可评估（氟尿嘧啶放射治疗，n = 155；mFOLFOX6 放射治疗，n = 157；mFOLFOX6，n = 163）。在氟尿嘧啶放疗组、mFOLFOX6放疗组和mFOLFOX6组中，病理完全缓解率（pCR）分别为14.0%、27.5%和6.6%，降期（ypStage 0至1）的患者分别为37.1%、56.4%和35.5%。接受放疗的患者出现更高的毒性反应和更多的术后并发症。结论基于FOLFOX6的术前放化疗比基于氟尿嘧啶的治疗具有更高的pCR率。围手术期单独使用 mFOLFOX6 的结果比放化疗差，pCR 率较低，但降期率与氟尿嘧啶放疗相似，且毒性较小，术后并发症也较少。 (C) 2016 年美国临床肿瘤学会
PurposeTotal mesorectal excision with fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy is a standard treatment of locally advanced rectal cancer. This study investigated the addition of oxaliplatin with and without preoperative radiotherapy.MethodsIn this multicenter, open-label, phase III trial, we randomly assigned (1:1:1) Chinese adults (age 18 to 75 years) with locally advanced stage II/III rectal cancer to three treatments: five 2-week cycles of infusional fluorouracil (leucovorin 400 mg/m(2), fluorouracil 400 mg/m(2), and fluorouracil 2.4 g/m(2) over 48 h) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 through 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m(2) on day 1 of each cycle (modified FOLFOX6 [mFOLFOX6]), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. Random assignment was performed by using computer-generated block randomization codes. The primary end point was 3-year disease-free survival. Secondary end points of histopathologic response and toxicity are reported.ResultsA total of 495 patients were enrolled from June 2010 to February 2015; 475 were evaluable (fluorouracil-radiotherapy, n = 155; mFOLFOX6-radiotherapy, n = 157; mFOLFOX6, n = 163). In the fluorouracil-radiotherapy, mFOLFOX6-radiotherapy, and mFOLFOX6 groups, the rate of pathologic complete response (pCR) was 14.0%, 27.5%, and 6.6%, and downstaging (ypStage 0 to 1) was achieved by 37.1%, 56.4%, and 35.5% of patients, respectively. Higher toxicity and more postoperative complications were observed in patients who received radiotherapy.ConclusionmFOLFOX6-based preoperative chemoradiotherapy results in a higher pCR rate than fluorouracil-based treatment. Perioperative mFOLFOX6 alone had inferior results and a lower pCR rate than chemoradiotherapy but led to a similar downstaging rate as fluorouracil-radiotherapy, with less toxicity and fewer postoperative complications. (C) 2016 by American Society of Clinical Oncology