Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial

被引：292

作者：

Deng, Yanhong ^{[1
]}

Chi, Pan ^{[2
]}

Lan, Ping ^{[1
]}

Wang, Lei ^{[1
]}

Chen, Weiqing ^{[3
]}

Cui, Long ^{[4
]}

Chen, Daoda ^{[5
]}

Cao, Jie ^{[6
]}

Wei, Hongbo ^{[7
]}

Peng, Xiang ^{[8
]}

Huang, Zonghai ^{[9
]}

Cai, Guanfu ^{[10
]}

Zhao, Ren ^{[11
]}

Huang, Zhongcheng ^{[12
]}

Xu, Lin ^{[13
]}

Zhou, Hongfeng ^{[14
]}

Wei, Yisheng ^{[15
]}

Zhang, Hao ^{[16
]}

Zheng, Jian ^{[1
]}

Huang, Yan ^{[1
]}

Zhou, Zhiyang ^{[1
]}

Cai, Yue ^{[1
]}

Kang, Liang ^{[1
]}

Huang, Meijin ^{[1
]}

Wu, Xiaojian ^{[1
]}

Peng, Junsheng ^{[1
]}

Ren, Donglin ^{[1
]}

Wang, Jianping ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Affiliated Hosp 6, Guangdong Prov Key Lab Colorectal & Pelv Floor Di, Guangzhou, Peoples R China

[2] Fujian Med Univ, Union Hosp, Fuzhou, Peoples R China

[3] Sun Yat Sen Univ, Sch Publ Hlth, Guangzhou, Peoples R China

[4] Shanghai Jiao Tong Univ, Xinhua Hosp, Shanghai, Peoples R China

[5] Huazhong Univ Sci & Technol, Xiehe Hosp, Wuhan, Peoples R China

[6] First Peoples Hosp, Guangzhou, Peoples R China

[7] Sun Yat Sen Univ, Affiliated Hosp 3, Guangzhou, Peoples R China

[8] First Peoples Hosp, Foshan, Peoples R China

[9] Nanfang Univ Med Sci, Zhujiang Hosp, Guangzhou, Peoples R China

[10] Guangdong Prov Peoples Hosp, Guangzhou, Peoples R China

[11] Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai, Peoples R China

[12] Gen Hosp, Changsha, Hunan, Peoples R China

[13] Xiamen Univ, Affiliated Hosp 1, Xiamen, Peoples R China

[14] Guangzhou Mil Command, Guangzhou Gen Hosp, Guangzhou, Peoples R China

[15] Guangzhou Med Univ, Affiliated Hosp 2, Guangzhou, Peoples R China

[16] Xinhua Hosp, Dongguan, Peoples R China

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2019年 / 37卷 / 34期

关键词：

TOTAL MESORECTAL EXCISION; PREOPERATIVE CHEMORADIOTHERAPY; POSTOPERATIVE CHEMOTHERAPY; GERMAN CAO/ARO/AIO-04; TUMOR RESPONSE; OPEN-LABEL; OXALIPLATIN; RADIOTHERAPY; LEUCOVORIN; MULTICENTER;

D O I：

10.1200/JCO.18.02309

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSE In the multicenter, open-label, phase III FOWARC trial, modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus radiotherapy resulted in a higher pathologic complete response rate than fluorouracil plus radiotherapy in Chinese patients with locally advanced rectal cancer. Here, we report the final results. METHODS Adults ages 18 to 75 years with stage II/III rectal cancer were randomly assigned (1:1:1) to five cycles of infusional fluorouracil (leucovorin 400 mg/m(2), fluorouracil 400 mg/m(2), and fluorouracil 2.4 g/m(2) over 48 hours) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 to 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 (mFOLFOX6), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. The primary end point was 3-year disease-free survival (DFS). RESULTS In total, 495 patients were randomly assigned to treatment. After a median follow-up of 45.2 months, DFS events were reported in 46, 39, and 46 patients in the fluorouracil plus radiotherapy, mFOLFOX6 plus radiotherapy, and mFOLFOX6 arms. In each arm, the probability of 3-year DFS was 72.9%, 77.2%, and 73.5% (P = .709 by the log-rank test), the 3-year probability of local recurrence after R0/1 resection was 8.0%, 7.0%, and 8.3% (P = .873 by the log-rank test), and the 3-year overall survival rate was 91.3%, 89.1%, and 90.7% (P = .971 by log-rank test), respectively. CONCLUSION mFOLFOX6, with or without radiation, did not significantly improve 3-year DFS versus fluorouracil with radiation in patients with locally advanced rectal cancer. No significant difference in outcomes was found between mFOLFOX6 without radiotherapy and fluorouracil with radiotherapy, which requires additional investigation of the role of radiotherapy in these regimens. (C) 2019 by American Society of Clinical Oncology

引用

页码：3223 / +

页数：13

共 27 条

[1] Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial [J].

Allegra, Carmen J. ;

Yothers, Greg ;

O'Connell, Michael J. ;

Beart, Robert W. ;

Wozniak, Timothy F. ;

Pitot, Henry C. ;

Shields, Anthony F. ;

Landry, Jerome C. ;

Ryan, David P. ;

Arora, Amit ;

Evans, Lisa S. ;

Bahary, Nathan ;

Soori, Gamini ;

Eakle, Janice F. ;

Robertson, John M. ;

Moore, Dennis F., Jr. ;

Mullane, Michael R. ;

Marchello, Benjamin T. ;

Ward, Patrick J. ;

Sharif, Saima ;

Roh, Mark S. ;

Wolmark, Norman .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2015, 107 (11)

[2] Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer [J].

Andre, T ;

Boni, C ;

Mounedji-Boudiaf, L ;

Navarro, M ;

Tabernero, J ;

Hickish, T ;

Topham, C ;

Zaninelli, M ;

Clingan, P ;

Bridgewater, J ;

Tabah-Fisch, I ;

de Gramont, A .

NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (23) :2343-2351

[3] Primary Tumor Response to Preoperative Chemoradiation With or Without Oxaliplatin in Locally Advanced Rectal Cancer: Pathologic Results of the STAR-01 Randomized Phase III Trial [J].

Aschele, Carlo ;

Cionini, Luca ;

Lonardi, Sara ;

Pinto, Carmine ;

Cordio, Stefano ;

Rosati, Gerardo ;

Artale, Salvatore ;

Tagliagambe, Angiolo ;

Ambrosini, Giovanni ;

Rosetti, Paola ;

Bonetti, Andrea ;

Negru, Maria Emanuela ;

Tronconi, Maria Chiara ;

Luppi, Gabriele ;

Silvano, Giovanni ;

Corsi, Domenico Cristiano ;

Bochicchio, Anna Maria ;

Chiaulon, Germana ;

Gallo, Maurizio ;

Boni, Luca .

JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (20) :2773-2780

[4] Late toxicities and clinical outcome at 5 years of the ACCORD 12/0405-PRODIGE 02 trial comparing two neoadjuvant chemoradiotherapy regimens for intermediate-risk rectal cancer [J].

Azria, D. ;

Doyen, J. ;

Jarlier, M. ;

Martel-Lafay, I. ;

Hennequin, C. ;

Etienne, P. ;

Vendrely, V. ;

Francois, E. ;

de la Roche, G. ;

Bouche, O. ;

Mirabel, X. ;

Denis, B. ;

Mineur, L. ;

Berdah, J. ;

Mahe, M. ;

Becouran, Y. ;

Dupuis, O. ;

Lledo, G. ;

Seitz, J. ;

Bedenne, L. ;

Gourgou-Bourgade, S. ;

Juzyna, B. ;

Conroy, T. ;

Gerard, J. .

ANNALS OF ONCOLOGY, 2017, 28 (10) :2436-2442

[5] Rectal Cancer, Version 2.2018 Clinical Practice Guidelines in Oncology [J].

Benson, Al B., III ;

Venook, Alan P. ;

Al-Hawary, Mahmoud M. ;

Cederquist, Lynette ;

Chen, Yi-Jen ;

Ciombor, Kristen K. ;

Cohen, Stacey ;

Cooper, Harry S. ;

Deming, Dustin ;

Engstrom, Paul F. ;

Grem, Jean L. ;

Grothey, Axel ;

Hochster, Howard S. ;

Hoffe, Sarah ;

Hunt, Steven ;

Kamel, Ahmed ;

Kirilcuk, Natalie ;

Krishnamurthi, Smitha ;

Messersmith, Wells A. ;

Meyerhardt, Jeffrey ;

Mulcahy, Mary F. ;

Murphy, James D. ;

Nurkin, Steven ;

Saltz, Leonard ;

Sharma, Sunil ;

Shibata, David ;

Skibber, John M. ;

Sofocleous, Constantinos T. ;

Stoffel, Elena M. ;

Stotsky-Himelfarb, Eden ;

Willett, Christopher G. ;

Wuthrick, Evan ;

Gregory, Kristina M. ;

Gurski, Lisa ;

Freedman-Cass, Deborah A. .

JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK, 2018, 16 (07) :874-901

[6] Watch-and-Wait as a Therapeutic Strategy in Rectal Cancer [J].

Bernier, Laurence ;

Balyasnikova, Svetlana ;

Tait, Diana ;

Brown, Gina .

CURRENT COLORECTAL CANCER REPORTS, 2018, 14 (02) :37-55

[7] LATE SIDE EFFECTS AND QUALITY OF LIFE AFTER RADIOTHERAPY FOR RECTAL CANCER [J].

Bruheim, Kjersti ;

Guren, Marianne G. ;

Skovlund, Eva ;

Hjermstad, Marianne J. ;

Dahl, Olav ;

Frykholm, Gunilla ;

Carlsen, Erik ;

Tveit, Kjell Magne .

INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2010, 76 (04) :1005-1011

[8] Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer [J].

De Caluwe, Laura ;

Van Nieuwenhove, Yves ;

Ceelen, Wim P. .

COCHRANE DATABASE OF SYSTEMATIC REVIEWS, 2013, (02)

[9] 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 [J].

Deng, Yanhong ;

Chi, Pan ;

Lan, Ping ;

Wang, Lei ;

Chen, Weiqing ;

Cui, Long ;

Chen, Daoda ;

Cao, Jie ;

Wei, Hongbo ;

Peng, Xiang ;

Huang, Zonghai ;

Cai, Guanfu ;

Zhao, Ren ;

Huang, Zhongcheng ;

Xu, Lin ;

Zhou, Hongfeng ;

Wei, Yisheng ;

Zhang, Hao ;

Zheng, Jian ;

Huang, Yan ;

Zhou, Zhiyang ;

Cai, Yue ;

Kang, Liang ;

Huang, Meijin ;

Peng, Junsheng ;

Ren, Donglin ;

Wang, Jianping .

JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (27) :3300-+

[10] Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers:: Results of FFCD 9203 [J].

Gerard, Jean-Pierre ;

Conroy, Thierry ;

Bonnetain, Franck ;

Bouche, Olivier ;

Chapet, Olivier ;

Closon-Dejardin, Marie-Therese ;

Untereiner, Michel ;

Leduc, Bernard ;

Francois, Eric ;

Maurel, Jean ;

Seitz, Jean-Francois ;

Buecher, Bruno ;

Mackiewicz, Remy ;

Ducreux, Michel ;

Bedenne, Laurent .

JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (28) :4620-4625

← 1 2 3 →