Neoadjuvant FOLFOX6 Chemotherapy With or Without Radiation in Rectal Cancer

Summary

RATIONALE: Preoperative 5-Fu based chemoradiation has become standard treatment for stage 2/3 rectal cancer. However whether these patients, especially T3N0-1M0 patients, really need radiation for local control after total mesentery excision being applied in routine practice is still unknown. And whether new drugs adding in can achieve better local and distant control is worth investigating. PURPOSE: This randomized phase II trial is studying 5Fu based radiation therapy or FOLFOX based radiation or FOLFOX alone, comparing them to see how well they work when given before surgery in treating patients with intermediate risk resectable rectal cancer. It is not yet known whether 5-Fu based or FOLFOX based radiation therapy or even FOLFOX alone is more effective in treating rectal cancer.

Timeline

Start

2010-06

Primary completion

2017-06

Completion

2020-06

Outcome

Missed primary endpoint

paper mFOLFOX6, with or without radiation, did not significantly improve 3-year DFS versus fluorouracil with radiation in patients with locally advanced rectal cancer. PMID 31557064 ↗

paper In each arm, the probability of 3-year DFS was 72.9%, 77.2%, and 73.5% (P = .709 by the log-rank test), PMID 31557064 ↗

Publications

• Zhang T, Shi L, Jian L, Jiang J, Qiu Y, Xie F, Zhang J, Peng H, Zhong L, Chen Y, Zhong Y, Deng Y; FOWARC Group. Clinical Benefit and Cost-Effectiveness of FOLFOX Versus LCCRT in Neoadjuvant Treatment for Patients with Locally Advanced Rectal Cancer: An Economic Analysis of the FOWARC and PROSPECT Trial. Ann Surg Oncol. 2026 May;33(5):3814-3826. doi: 10.1245/s10434-025-18802-8. Epub 2025 Dec 11.
• Wan H, Weng J, Cai J, Chen Z, Li P, Han J, Li Z, Wan Z, Yuan Z, Gan Y, Huang M, Li X, Li T, Liu X, Wang X, Yu H, Liu B, Lin J, Luo Y. Nodal Downstaging in Patients With Rectal Cancer: Survival Is Promising if YpN0 Is Achieved. Dis Colon Rectum. 2025 Oct 1;68(10):1162-1171. doi: 10.1097/DCR.0000000000003846. Epub 2025 Jul 8.
• Shi L, Zhang J, Deng Y. Associations of pretreatment emotional distress with adherence to therapy for patients with locally advanced rectal cancer: a post hoc analysis of the Chinese FOWARC phase 3 randomized clinical trial. BMC Med. 2025 May 21;23(1):293. doi: 10.1186/s12916-025-04128-5.
• Zhang J, Chi P, Shi L, Cui L, Gao J, Li W, Wei H, Cheng L, Huang Z, Cai G, Zhao R, Huang Z, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Cai Y, Zhou Z, Kang L, Huang M, Wu X, Peng J, Ren D, Lan P, Wang J, Deng Y. Neoadjuvant Modified Infusional Fluorouracil, Leucovorin, and Oxaliplatin With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Updated Results of the FOWARC Study After a Median Follow-Up of 10 Years. J Clin Oncol. 2025 Feb 20;43(6):633-640. doi: 10.1200/JCO-24-01676. Epub 2024 Dec 13.
• Li L, Xu B, Zhuang Z, Li J, Hu Y, Yang H, Wang X, Lin J, Zhou R, Chen W, Ran D, Huang M, Wang D, Luo Y, Yu H. Accurate tumor segmentation and treatment outcome prediction with DeepTOP. Radiother Oncol. 2023 Jun;183:109550. doi: 10.1016/j.radonc.2023.109550. Epub 2023 Feb 21.
• Xie Y, Lin J, Wang X, Wang P, Zhuang Z, Zou Q, Cai D, Huang Z, Bai L, Tang G, Huang M, Wang J, Yu H, Luo Y. The Addition of Preoperative Radiation Is Insufficient for Lateral Pelvic Control in a Subgroup of Patients With Low Locally Advanced Rectal Cancer: A Post Hoc Study of a Randomized Controlled Trial. Dis Colon Rectum. 2021 Nov 1;64(11):1321-1330. doi: 10.1097/DCR.0000000000001935.
• Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Wu X, Peng J, Ren D, Wang J. Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial. J Clin Oncol. 2019 Dec 1;37(34):3223-3233. doi: 10.1200/JCO.18.02309. Epub 2019 Sep 26.
• Hu H, Huang J, Lan P, Wang L, Huang M, Wang J, Deng Y. CEA clearance pattern as a predictor of tumor response to neoadjuvant treatment in rectal cancer: a post-hoc analysis of FOWARC trial. BMC Cancer. 2018 Nov 20;18(1):1145. doi: 10.1186/s12885-018-4997-y.
• Qin Q, Ma T, Deng Y, Zheng J, Zhou Z, Wang H, Wang L, Wang J. Impact of Preoperative Radiotherapy on Anastomotic Leakage and Stenosis After Rectal Cancer Resection: Post Hoc Analysis of a Randomized Controlled Trial. Dis Colon Rectum. 2016 Oct;59(10):934-42. doi: 10.1097/DCR.0000000000000665.
• Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Peng J, Ren D, Wang J. 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 Clin Oncol. 2016 Sep 20;34(27):3300-7. doi: 10.1200/JCO.2016.66.6198. Epub 2016 Aug 1.
• Huang M, Lin J, Yu X, Chen S, Kang L, Deng Y, Zheng J, Luo Y, Wang L, Lan P, Wang J. Erectile and urinary function in men with rectal cancer treated by neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy alone: a randomized trial report. Int J Colorectal Dis. 2016 Jul;31(7):1349-57. doi: 10.1007/s00384-016-2605-7. Epub 2016 Jun 6.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Oxaliplatin	Small molecule	85 mg/m2	Intravenous
Comparator	fluorouracil	Small molecule	400 mg/m2	Intravenous
Comparator	fluorouracil	Small molecule	2.4 g	Intravenous

Indications