Neoadjuvant 5-FU or capecitabine plus radiation with or without oxaliplatin in rectal cancer patients: A phase III randomized clinical trial

Carmen J. Allegra, Greg Yothers, Michael J. O'Connell, Robert W. Beart, Timothy F. Wozniak, Henry C. Pitot, Anthony F. Shields, Jerome C. Landry, David P. Ryan, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini Soori, Janice F. Eakle, John M. Robertson, Dennis F. Moore, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Saima SharifMark S. Roh, Norman Wolmark

Research output: Contribution to journalArticlepeer-review

146 Scopus citations


Background: National Surgical Adjuvant Breast and Bowel Project R-04 was designed to determine whether the oral fluoropyrimidine capecitabine could be substituted for continuous infusion 5-FU in the curative setting of stage II/III rectal cancer during neoadjuvant radiation therapy and whether the addition of oxaliplatin could further enhance the activity of fluoropyrimidine-sensitized radiation. Methods: Patients with clinical stage II or III rectal cancer undergoing preoperative radiation were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU or oral capecitabine with or without oxaliplatin. The primary endpoint was local-regional tumor control. Time-to-event endpoint distributions were estimated using the Kaplan-Meier method. Hazard ratios were estimated from Cox proportional hazard models. All statistical tests were twosided. Results: Among 1608 randomized patients there were no statistically significant differences between regimens using 5-FU vs capecitabine in three-year local-regional tumor event rates (11.2% vs 11.8%), 5-year DFS (66.4% vs 67.7%), or 5-year OS (79.9% vs 80.8%); or for oxaliplatin vs no oxaliplatin for the three endpoints of local-regional events, DFS, and OS (11.2% vs 12.1%, 69.2% vs 64.2%, and 81.3% vs 79.0%). The addition of oxaliplatin was associated with statistically significantly more overall and grade 3-4 diarrhea (P < .0001). Three-year rates of local-regional recurrence among patients who underwent R0 resection ranged from 3.1 to 5.1% depending on the study arm.

Original languageEnglish (US)
JournalJournal of the National Cancer Institute
Issue number11
StatePublished - Nov 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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