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Consolidation mFOLFOX6 Chemotherapy After Chemoradiotherapy Improves Survival in Patients With Locally Advanced Rectal Cancer

Final Results of a Multicenter Phase II Trial

Marco, Michael R., M.D., M.Sc.1; Zhou, Lihong, M.D.1; Patil, Sujata, Ph.D.2; Marcet, Jorge E., M.D.3; Varma, Madhulika G., M.D.4; Oommen, Samuel, M.D.5; Cataldo, Peter A., M.D.6; Hunt, Steven R., M.D.7; Kumar, Anjali, M.D., M.P.H.8; Herzig, Daniel O., M.D.9; Fichera, Alessandro, M.D.10; Polite, Blase N., M.D.11; Hyman, Neil H., M.D.12; Ternent, Charles A., M.D.13; Stamos, Michael J., M.D.14; Pigazzi, Alessio, M.D., Ph.D.14; Dietz, David, M.D.15; Yakunina, Yuliya, B.A.1; Pelossof, Raphael, Ph.D.1; Garcia-Aguilar, Julio, M.D., Ph.D.1 For the Timing of Rectal Cancer Response to Chemoradiation Consortium

doi: 10.1097/DCR.0000000000001207
Original Contributions: Colorectal Cancer
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BACKGROUND: Adding modified FOLFOX6 (folinic acid, fluorouracil, and oxaliplatin) after chemoradiotherapy and lengthening the chemoradiotherapy-to-surgery interval is associated with an increase in the proportion of rectal cancer patients with a pathological complete response.

OBJECTIVE: The purpose of this study was to analyze disease-free and overall survival.

DESIGN: This was a nonrandomized phase II trial.

SETTINGS: The study was conducted at multiple institutions.

PATIENTS: Four sequential study groups with stage II or III rectal cancer were included.

INTERVENTION: All of the patients received 50 Gy of radiation with concurrent continuous infusion of fluorouracil for 5 weeks. Patients in each group received 0, 2, 4, or 6 cycles of modified FOLFOX6 after chemoradiation and before total mesorectal excision. Patients were recommended to receive adjuvant chemotherapy after surgery to complete a total of 8 cycles of modified FOLFOX6.

MAIN OUTCOME MEASURES: The trial was powered to detect differences in pathological complete response, which was reported previously. Disease-free and overall survival are the main outcomes for the current study.

RESULTS: Of 259 patients, 211 had a complete follow-up. Median follow-up was 59 months (range, 9–125 mo). The mean number of total chemotherapy cycles differed among the 4 groups (p = 0.002), because one third of patients in the group assigned to no preoperative FOLFOX did not receive any adjuvant chemotherapy. Disease-free survival was significantly associated with study group, ypTNM stage, and pathological complete response (p = 0.004, <0.001, and 0.001). A secondary analysis including only patients who received ≥1 cycle of FOLFOX still showed differences in survival between study groups (p = 0.03).

LIMITATIONS: The trial was not randomized and was not powered to show differences in survival. Survival data were not available for 19% of the patients.

CONCLUSIONS: Adding modified FOLFOX6 after chemoradiotherapy and before total mesorectal excision increases compliance with systemic chemotherapy and disease-free survival in patients with locally advanced rectal cancer. Neoadjuvant consolidation chemotherapy may have benefits beyond increasing pathological complete response rates. See Video Abstract at

1 Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York

2 Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York

3 Department of Surgery, University of South Florida, Tampa, Florida

4 Department of Surgery, University of California, San Francisco, San Francisco, California

5 Department of Surgery, John Muir Health, Concord, California

6 Department of Surgery, University of Vermont, Burlington, Vermont

7 Department of Surgery, Washington University, St. Louis, Missouri

8 Department of Surgery, Washington State University, Spokane, Washington

9 Department of Surgery, Oregon Health & Science University, Portland, Oregon

10 Department of Surgery, University of North Carolina, Chapel Hill, North Carolina

11 Department of Medicine, University of Chicago, Chicago, Illinois

12 Department of Surgery, University of Chicago, Chicago, Illinois

13 Department of Surgery, Creighton University Medical Center, University of Nebraska College of Medicine, Omaha, Nebraska

14 Department of Surgery, University of California, Irvine, Irvine, California

15 Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML and PDF versions of this article on the journal’s Web site (

Funding/Support: This work was supported by National Cancer Institute grants R01 CA090559 and P30 CA008748.

Financial Disclosure: None reported.

Podium presentation at the meeting of The American Society of Colon and Rectal Surgeons, Nashville, TN, May 19 to 23, 2018.

Correspondence: Julio Garcia-Aguilar, M.D., Ph.D., Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065. E-mail:

© 2018 The American Society of Colon and Rectal Surgeons