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

• Type of Material: Article
• Authors: Michael J. O'Connell, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; Linda H. Colangelo, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; Robert W. Beart, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; Nicholas J. Petrelli, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; Carme J. Allegra, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; Saima Sharif, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; Henry C. Pitot, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; Anthony F. Shields, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David P. Ryan, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; David S. Parda, Allegheny General Hospital; Mohammed Mohiuddin, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; Amit Arora, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; Lisa S. Evans, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; Nathan Bahary, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; Gamini Soori, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; Janice Eakle, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; John M. Robertson, National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; Jerome Landry, Emory University
• Language: English
• Date: 2014-06-20
• Publisher: American Society of Clinical Oncology
• Publication Version: Final Published Version
• Copyright Statement: © 2014 by American Society of Clinical Oncology.
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.2013.53.7753
• Title of Journal or Parent Work: Journal of Clinical Oncology
• Volume: 32
• Issue: 18
• Start Page: 1927
• End Page: 1934
• Grant/Funding Information: Supported by Public Health Service Grants No. U10-CA-12027, U10-CA-37377, U10-CA-69651, and U-10-CA-69974 from the National Cancer Institute, US Department of Health and Human Services; Cancer Support Grant No. CA22453 from the National Institutes of Health (A.F.S.); Southwest Oncology Group Treatment Grant No. CA032102 from the National Institutes of Health (A.F.S.); and Sanofi-Synthelabo and Roche Laboratories.
• Keywords: CHEMOTHERAPY; RANDOMIZED-TRIAL; LEUCOVORIN; RADIOTHERAPY; Science & Technology; ADENOCARCINOMA; FLUOROURACIL; CHEMORADIOTHERAPY; Life Sciences & Biomedicine; THERAPY; Oncology; 5-FLUOROURACIL; COLORECTAL-CANCER
• Research Categories: Health Sciences, Oncology

Abstract

Purpose: 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 and Methods: 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/m2, 5 days per week), with or without intravenous oxaliplatin (50 mg/m2 once per week for 5 weeks) or oral capecitabine (825 mg/m2 twice per day, 5 days per week), with or without oxaliplatin (50 mg/m2 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). Results: 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). Conclusion: 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.