Yanhong Deng1, Pan Chi1, Ping Lan1, Lei Wang1, Weiqing Chen1, Long Cui1, Daoda Chen1, Jie Cao1, Hongbo Wei1, Xiang Peng1, Zonghai Huang1, Guanfu Cai1, Ren Zhao1, Zhongcheng Huang1, Lin Xu1, Hongfeng Zhou1, Yisheng Wei1, Hao Zhang1, Jian Zheng1, Yan Huang1, Zhiyang Zhou1, Yue Cai1, Liang Kang1, Meijin Huang1, Junsheng Peng1, Donglin Ren1, Jianping Wang2. 1. Yanhong Deng, Ping Lan, Lei Wang, Jian Zheng, Yan Huang, Zhiyang Zhou, Yue Cai, Liang Kang, Meijin Huang, Junsheng Peng, Donglin Ren, and Jianping Wang, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases; Weiqing Chen, Medical Statistics of Sun Yat-sen University; Jie Cao, Guangzhou First People's Hospital; HongboWei, The Third Affiliated Hospital of Sun Yat-sen University; Zonghai Huang, Zhujiang Hospital of Southem Medical University; Guanfu Cai, Guangdong General Hospital; Hongfeng Zhou, General Hospital of Guangzhou Military Command PLA; Yisheng Wei, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou; Pan Chi, Fujian Medical University Union Hospital, Fuzhou; Long Cui, Xin Hua Hospital of Shanghai Jiao Tong University School of Medicine; Ren Zhao, Rui Jin Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai; Daoda Chen, Union Hospital Tongji Medical College of Huazhong University of Science and Technology, Wuhan; Xiang Peng, The First People's Hospital, Foshan; Zhongcheng Huang, Hunan Provincial People's Hospital, Changsha; Lin Xu, The First Affiliated Hospital of Xiamen University, Xiamen; and Hao Zhang, Dongguan Kanghua Hospital, Dongguan, China. 2. Yanhong Deng, Ping Lan, Lei Wang, Jian Zheng, Yan Huang, Zhiyang Zhou, Yue Cai, Liang Kang, Meijin Huang, Junsheng Peng, Donglin Ren, and Jianping Wang, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases; Weiqing Chen, Medical Statistics of Sun Yat-sen University; Jie Cao, Guangzhou First People's Hospital; HongboWei, The Third Affiliated Hospital of Sun Yat-sen University; Zonghai Huang, Zhujiang Hospital of Southem Medical University; Guanfu Cai, Guangdong General Hospital; Hongfeng Zhou, General Hospital of Guangzhou Military Command PLA; Yisheng Wei, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou; Pan Chi, Fujian Medical University Union Hospital, Fuzhou; Long Cui, Xin Hua Hospital of Shanghai Jiao Tong University School of Medicine; Ren Zhao, Rui Jin Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai; Daoda Chen, Union Hospital Tongji Medical College of Huazhong University of Science and Technology, Wuhan; Xiang Peng, The First People's Hospital, Foshan; Zhongcheng Huang, Hunan Provincial People's Hospital, Changsha; Lin Xu, The First Affiliated Hospital of Xiamen University, Xiamen; and Hao Zhang, Dongguan Kanghua Hospital, Dongguan, China. wangjpgz@126.com.
Abstract
PURPOSE:Total 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. METHODS: In 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 ofinfusional 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. RESULTS:A 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. CONCLUSION:mFOLFOX6-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.
RCT Entities:
PURPOSE: Total 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. METHODS: In 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. RESULTS: A 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. CONCLUSION:mFOLFOX6-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.