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J Clin Oncol. 2014 Jun 20;32(18):1927-34. doi: 10.1200/JCO.2013.53.7753. Epub 2014 May 5.

Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04.

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Michael J. O'Connell, Linda H. Colangelo, Robert W. Beart, Nicholas J. Petrelli, Carmen J. Allegra, Saima Sharif, Henry C. Pitot, Anthony F. Shields, David S. Parda, Mohammed Mohiuddin, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini S. Soori, Janice Eakle, John M. Robertson, Dennis F. Moore Jr, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Timothy F. Wozniak, Mark S. Roh, Greg Yothers, Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Nathan Bahary, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, Pittsburgh, PA; Robert W. Beart, Colorectal Surgery Institute, Glendale Memorial Hospital, Glendale; Amit Arora, Kaiser Permanente Hayward, Hayward, CA; Nicholas J. Petrelli, Timothy F. Wozniak, Helen F. Graham Cancer Center at Christiana Care Health Service, Newark, DE; Carmen J. Allegra, University of Florida, Gainesville; Janice Eakle, Florida Cancer Specialists, Sarasota; Mark S. Roh, MD Anderson Cancer Center Orlando Health, Orlando, FL; Henry C. Pitot, Mayo Clinic, Rochester, MN; Anthony F. Shields, Karmanos Cancer Institute/Southwest Oncology Group, Detroit; John M. Robertson, Beaumont Hospital System, Royal Oak, MI; Jerome C. Landry, Eastern Cooperative Oncology Group/Emory University, Winship Cancer Institute, Atlanta, GA; David P. Ryan, Massachusetts General Hospital Cancer Center, Boston, MA; Lisa S. Evans, Community Clinical Oncology Program, Southeast CCC Novant Health Derrick L. Davis Forsyth Medical Center, Winston-Salem, NC; Gamini S. Soori, Missouri Valley Cancer Consortium Community Clinical Oncology Program, Omaha, NE; Dennis Moore Jr, Community Clinical Oncology Program, Wichita/St Francis Regional Medical Center/Via Christi Regional Medical Center, Wichita, KS; Michael R. Mullane, Minority-Based Community Clinical Oncology Program John H. Stroger Jr Hospital



The optimal chemotherapy regimen administered concurrently with preoperative radiation therapy (RT) for patients with rectal cancer is unknown. National Surgical Adjuvant Breast and Bowel Project trial R-04 compared four chemotherapy regimens administered concomitantly with RT.


Patients with clinical stage II or III rectal cancer who were undergoing preoperative RT (45 Gy in 25 fractions over 5 weeks plus a boost of 5.4 Gy to 10.8 Gy in three to six daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous intravenous infusional fluorouracil (CVI FU; 225 mg/m(2), 5 days per week), with or without intravenous oxaliplatin (50 mg/m(2) once per week for 5 weeks) or oral capecitabine (825 mg/m(2) twice per day, 5 days per week), with or without oxaliplatin (50 mg/m(2) once per week for 5 weeks). Before random assignment, the surgeon indicated whether the patient was eligible for sphincter-sparing surgery based on clinical staging. The surgical end points were complete pathologic response (pCR), sphincter-sparing surgery, and surgical downstaging (conversion to sphincter-sparing surgery).


From September 2004 to August 2010, 1,608 patients were randomly assigned. No significant differences in the rates of pCR, sphincter-sparing surgery, or surgical downstaging were identified between the CVI FU and capecitabine regimens or between the two regimens with or without oxaliplatin. Patients treated with oxaliplatin experienced significantly more grade 3 or 4 diarrhea (P < .001).


Administering capecitabine with preoperative RT achieved similar rates of pCR, sphincter-sparing surgery, and surgical downstaging compared with CVI FU. Adding oxaliplatin did not improve surgical outcomes but added significant toxicity. The definitive analysis of local tumor control, disease-free survival, and overall survival will be performed when the protocol-specified number of events has occurred.


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