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- Title
Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial.
- Authors
Allegra, Carmen J.; Yothers, Greg; O'Connell, Michael J.; Beart, Robert W.; Wozniak, Timothy F.; Pitot, Henry C.; Shields, Anthony F.; Landry, Jerome C.; Ryan, David P.; Arora, Amit; Evans, Lisa S.; Bahary, Nathan; Soori, Gamini; Eakle, Janice F.; Robertson, John M.; Moore Jr, Dennis F.; Mullane, Michael R.; Marchello, Benjamin T.; Ward, Patrick J.; Sharif, Saima
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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 two-sided.<bold>Results: </bold>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.<bold>Conclusions: </bold>Continuous infusion 5-FU produced outcomes for local-regional control, DFS, and OS similar to those obtained with oral capecitabine combined with radiation. This study establishes capecitabine as a standard of care in the pre-operative rectal setting. Oxaliplatin did not improve the local-regional failure rate, DFS, or OS for any patient risk group but did add considerable toxicity.
- Subjects
RECTAL cancer treatment; FLUOROPYRIMIDINES; RADIOTHERAPY; CANCER chemotherapy; DRUG therapy; THERAPEUTICS; ANTINEOPLASTIC agents; THERAPEUTIC use of antimetabolites; COMBINED modality therapy; DRUG administration; FLUOROURACIL; ORGANOPLATINUM compounds; RECTUM tumors; RESEARCH funding; RANDOMIZED controlled trials; TREATMENT effectiveness; DEOXYCYTIDINE
- Publication
JNCI: Journal of the National Cancer Institute, 2015, Vol 107, Issue 11, p1
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/djv248