Neoadjuvant 5-FU or capecitabine plus radiation with or without oxaliplatin in rectal cancer patients: A phase III randomized clinical trial

Carmen J. Allegra, Greg Yothers, Michael J. O'Connell, Robert W. Beart, Timothy F. Wozniak, Henry Clement Pitot, Anthony F. Shields, Jerome C. Landry, David P. Ryan, Amit Arora, Lisa S. Evans, Nathan Bahary, Gamini Soori, Janice F. Eakle, John M. Robertson, Dennis F. Moore, Michael R. Mullane, Benjamin T. Marchello, Patrick J. Ward, Saima SharifMark S. Roh, Norman Wolmark

Research output: Contribution to journalArticle

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Abstract

Background: 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. Methods: 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 twosided. Results: 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.

Original languageEnglish (US)
Article numberdjv248
JournalJournal of the National Cancer Institute
Volume107
Issue number11
DOIs
StatePublished - 2015

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oxaliplatin
Phase III Clinical Trials
Rectal Neoplasms
Fluorouracil
Randomized Controlled Trials
Radiation
Neoadjuvant Therapy
Proportional Hazards Models
Diarrhea
Neoplasms
Breast
Radiotherapy
Capecitabine
Recurrence
Drug Therapy

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

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Neoadjuvant 5-FU or capecitabine plus radiation with or without oxaliplatin in rectal cancer patients : A phase III randomized clinical trial. / Allegra, Carmen J.; Yothers, Greg; O'Connell, Michael J.; Beart, Robert W.; Wozniak, Timothy F.; Pitot, Henry Clement; 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, Dennis F.; Mullane, Michael R.; Marchello, Benjamin T.; Ward, Patrick J.; Sharif, Saima; Roh, Mark S.; Wolmark, Norman.

In: Journal of the National Cancer Institute, Vol. 107, No. 11, djv248, 2015.

Research output: Contribution to journalArticle

Allegra, CJ, Yothers, G, O'Connell, MJ, Beart, RW, Wozniak, TF, Pitot, HC, Shields, AF, Landry, JC, Ryan, DP, Arora, A, Evans, LS, Bahary, N, Soori, G, Eakle, JF, Robertson, JM, Moore, DF, Mullane, MR, Marchello, BT, Ward, PJ, Sharif, S, Roh, MS & Wolmark, N 2015, 'Neoadjuvant 5-FU or capecitabine plus radiation with or without oxaliplatin in rectal cancer patients: A phase III randomized clinical trial', Journal of the National Cancer Institute, vol. 107, no. 11, djv248. https://doi.org/10.1093/jnci/djv248
Allegra, Carmen J. ; Yothers, Greg ; O'Connell, Michael J. ; Beart, Robert W. ; Wozniak, Timothy F. ; Pitot, Henry Clement ; 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, Dennis F. ; Mullane, Michael R. ; Marchello, Benjamin T. ; Ward, Patrick J. ; Sharif, Saima ; Roh, Mark S. ; Wolmark, Norman. / Neoadjuvant 5-FU or capecitabine plus radiation with or without oxaliplatin in rectal cancer patients : A phase III randomized clinical trial. In: Journal of the National Cancer Institute. 2015 ; Vol. 107, No. 11.
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abstract = "Background: 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. Methods: 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 twosided. Results: 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.",
author = "Allegra, {Carmen J.} and Greg Yothers and O'Connell, {Michael J.} and Beart, {Robert W.} and Wozniak, {Timothy F.} and Pitot, {Henry Clement} and Shields, {Anthony F.} and Landry, {Jerome C.} and Ryan, {David P.} and Amit Arora and Evans, {Lisa S.} and Nathan Bahary and Gamini Soori and Eakle, {Janice F.} and Robertson, {John M.} and Moore, {Dennis F.} and Mullane, {Michael R.} and Marchello, {Benjamin T.} and Ward, {Patrick J.} and Saima Sharif and Roh, {Mark S.} and Norman Wolmark",
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TY - JOUR

T1 - Neoadjuvant 5-FU or capecitabine plus radiation with or without oxaliplatin in rectal cancer patients

T2 - A phase III randomized clinical trial

AU - Allegra, Carmen J.

AU - Yothers, Greg

AU - O'Connell, Michael J.

AU - Beart, Robert W.

AU - Wozniak, Timothy F.

AU - Pitot, Henry Clement

AU - Shields, Anthony F.

AU - Landry, Jerome C.

AU - Ryan, David P.

AU - Arora, Amit

AU - Evans, Lisa S.

AU - Bahary, Nathan

AU - Soori, Gamini

AU - Eakle, Janice F.

AU - Robertson, John M.

AU - Moore, Dennis F.

AU - Mullane, Michael R.

AU - Marchello, Benjamin T.

AU - Ward, Patrick J.

AU - Sharif, Saima

AU - Roh, Mark S.

AU - Wolmark, Norman

PY - 2015

Y1 - 2015

N2 - Background: 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. Methods: 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 twosided. Results: 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.

AB - Background: 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. Methods: 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 twosided. Results: 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.

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