Journal article
Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial
JNCI : Journal of the National Cancer Institute, Vol.107(11), p.1
11/2015
DOI: 10.1093/jnci/djv248
PMCID: PMC4849360
PMID: 26374429
Abstract
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.
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.
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.
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.
Details
- Title: Subtitle
- Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial
- Creators
- Carmen J Allegra - NRG OncologyGreg Yothers - University of PittsburghMichael J O'ConnellRobert W Beart - Glendale Memorial Hospital, Glendale, CATimothy F Wozniak - Christiana Care Health SystemHenry C Pitot - Mayo Clinic in FloridaAnthony F Shields - The Barbara Ann Karmanos Cancer InstituteJerome C Landry - Emory UniversityDavid P Ryan - Massachusetts General HospitalAmit Arora - Kaiser PermanenteLisa S Evans - Novant Health Forsyth Medical CenterNathan Bahary - University of PittsburghGamini Soori - NRG OncologyJanice F Eakle - NRG OncologyJohn M Robertson - Beaumont HospitalDennis F Moore Jr - Cancer Center of KansasMichael R Mullane - NRG OncologyBenjamin T Marchello - NRG OncologyPatrick J WardSaima Sharif - NRG OncologyMark S Roh - NRG OncologyNorman Wolmark - Allegheny General Hospital
- Resource Type
- Journal article
- Publication Details
- JNCI : Journal of the National Cancer Institute, Vol.107(11), p.1
- DOI
- 10.1093/jnci/djv248
- PMID
- 26374429
- PMCID
- PMC4849360
- ISSN
- 0027-8874
- eISSN
- 1460-2105
- Grant note
- U10 CA180822 / NCI NIH HHS U10 CA180867 / NCI NIH HHS UG1 CA189867 / NCI NIH HHS U10-CA180868 / NCI NIH HHS UG1-CA189867 / NCI NIH HHS U10-CA180822 / NCI NIH HHS U10-CA180820 / NCI NIH HHS U10-CA180821 / NCI NIH HHS U10-CA180888 / NCI NIH HHS U10 CA180820 / NCI NIH HHS
- Language
- English
- Date published
- 11/2015
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984363163802771
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