The impact of capecitabine and oxaliplatin in the preoperative multimodality treatment in patients with carcinoma of the rectum: NSABP R-04.

Gastrointestinal (Colorectal) Cancer
Session Type and Session Title: 
Oral Abstract Session, Gastrointestinal (Colorectal) Cancer
Abstract Number: 


J Clin Oncol 29: 2011 (suppl; abstr 3503)
M. S. Roh, G. A. Yothers, M. J. O'Connell, R. W. Beart, H. C. Pitot, A. F. Shields, D. S. Parda, S. Sharif, C. J. Allegra, N. J. Petrelli, J. C. Landry, D. P. Ryan, A. Arora, T. L. Evans, G. S. Soori, L. Chu, R. V. Landes, M. Mohiuddin, S. Lopa, N. Wolmark; NSABP; M. D. Anderson Cancer Center Orlando, Pittsburgh, PA; NSABP Biostatistical Center and University of Pittsburgh Graduate School of Public Health Department of Biostatistics, Pittsburgh, PA; National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA; NSABP; University of Southern California, Glendale, CA; Mayo Clinic, Rochester, MN; National Surgical Adjuvant Breast and Bowel Project; Karmanos Cancer Institute, Wayne State University, Detroit, MI; NSABP and Allegheny General Hospital, Pittsburgh, PA; National Surgical Adjuvant Breast and Bowel Project and Allegheny General Hospital, Pittsburgh, PA; University of Florida, Gainesville, FL; NSABP and the Helen F. Graham Cancer Center at Christiana Care Health System, Newark, DE; ECOG Emory University, Atlanta, GA; Division of Hematology and Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Kaiser Permanente, Hayward, CA; UPMC Cancer Center, Greensburg, PA; Missouri Valley Cancer Consotrium, Omaha, NE; NSABP; Florida Cancer Specialists, Sarasota, FL; William Beaumont Hospital, Royal Oak, MI; King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia; NSABP and the NSABP Biostatistical Center, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: The optimal chemotherapy regimen to be given concurrently with preop radiation therapy (RT) in patients with resectable adenocarcinoma of the rectum is unknown. NSABP R-04 compared the efficacy of 4 chemotherapy regimens administered concomitantly with preop RT. Methods: Patients with clinical stage II or III rectal cancer undergoing preop RT (4,500cGy in 25 fractions over 5 wk + boost of 540cGy-1080cGy in 3-6 daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous IV infusion (CVI) 5-FU (225mg/m2 5 days/wk), with or without IV oxaliplatin (OX) (50mg/m2 /wk x 5); oral capecitabine (CAPE) (825 mg/m2 BID 5 days/wk), with or without OX (50mg/m2/wk x 5). Prior to random assignment the surgeon indicated if the patient was eligible for sphincter-saving surgery (SSS) based on clinical staging. The endpoints were complete pathologic response (pCR), SSS, and surgical downstaging (SD, conversion to SSS). Results: From July 2004 to August 2010, 1,608 patients were randomly assigned. No significant differences in the rates of pCR, SSS, or SD were identified between the 5-FU and CAPE regimens or between the regimens, with and without OX (Table). Patients treated with OX experienced significantly more grade 3/4 diarrhea. Conclusions: Administration of capecitabine with preop RT achieved similar rates of pCR, SSS, and SD compared to CVI 5-FU. The addition of oxaliplatin did not improve preliminary outcomes but added significant toxicity. The definitive analysis of local tumor control will be performed in fall 2013. Funded by NCI PHS grants U10-CA-37377, U10-CA-69974, U10-CA-12027, U10-CA-69651, and U10-CA-25224 with support from sanofi-aventis US Inc. and Hoffmann La-Roche.

Endpoint 5-FU (± OX) CAPE (± OX) P value

pCR 135/719 = 18.8% 157/707 = 22.2% 0.12
SSS 445/727 = 61.2% 445/710 = 62.7% 0.59
SD 39/188 = 20.7% 43/187 = 23.0% 0.62
Grade 3/4 diarrhea 70/625 = 11.2% 68/628 = 10.8% 0.86

Endpoint (FU or CAPE) No OX (FU or CAPE) + OX P value
pCR 111/580 = 19.1% 121/578 = 20.9% 0.46
SSS 370/582 = 63.6% 353/584 = 60.4% 0.28
SD 35/152 = 23.0% 29/151 = 19.2% 0.48
Grade 3/4 diarrhea 41/622 = 6.6% 97/631 = 15.4% < 0.0001