Severe enteropathy among patients with stage II/III colon cancer treated on a randomized trial of bolus 5-fluorouracil/leucovorin plus or minus oxaliplatin

A prospective analysis

Authors

  • J. Philip Kuebler MD,

    1. National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, Pennsylvania
    2. Community Clinical Oncology Program (CCOP) Columbus, Ohio
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    • J. Philip Kuebler received honoraria from Sanofi-Aventis and Genentech and is on the advisory board of Sanofi-Aventis.

  • Linda Colangelo MD,

    1. Biostatistical Center, National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, Pennsylvania
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  • Michael J. O'Connell MD,

    Corresponding author
    1. National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, Pennsylvania
    • National Surgical Adjuvant Breast and Bowel Project (NSABP) East Commons Professional Bldg., Four Allegheny Center, 5th Fl., Pittsburgh, PA 15212
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    • Michael J. O'Connell was a consultant to and has received honoraria from Sanofi-Aventis.

    • Fax: (412) 330-4660

  • Roy E. Smith MD,

    1. Shadyside Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
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  • Greg Yothers MD,

    1. Biostatistical Center, National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, Pennsylvania
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  • Mirsada Begovic MD,

    1. Biostatistical Center, National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, Pennsylvania
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  • Bridget Robinson MD,

    1. Christchurch Hospital, Christchurch, New Zealand
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    • Dr. Robinson thanks the following coordinating center personnel and site investigators in Australia and New Zealand: AGITG: John Zalcberg, Michael Findlay; NHMRC Clinical Trials Centre: John Simes, Burcu Cakir, Haryana Dhillon; AGITG Site Investigators: David Goldstein, Sydney, Australia; Guy van Hazel, Perth, Australia; Etesham Abdi, Towoomba, Australia; Vinod Ganju, Melbourne, Australia. The authors thank Barbara C. Good, PhD, Director of Scientific Publications for the NSABP, for editorial assistance.

  • Thomas E. Seay MD,

    1. Atlanta Cancer Care, Atlanta, Georgia
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  • Norman Wolmark MD

    1. National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, Pennsylvania
    2. Allegheny General Hospital, Pittsburgh, Pennsylvania
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Abstract

BACKGROUND.

Cases of severe gastrointestinal toxicity were monitored prospectively during NSABP C-07, a randomized clinical trial of adjuvant therapy for patients with stage II/III colon cancer.

METHODS.

Patients were treated with weekly bolus 5-fluorouracil (5-FU) and leucovorin (FL; “Roswell Park Regimen”) or the same regimen plus oxaliplatin (FLOX).

RESULTS.

Of 1857 patients, 79 (4.3%) developed a syndrome of bowel wall injury (BWI, small or large) characterized by hospitalization for the management of severe diarrhea or dehydration and radiographic or endoscopic evidence of bowel wall thickening or ulceration. Fifty-one (64.6%) of these adverse events occurred in patients treated with FLOX and 28 (35.4%) in those treated with FL (P < .01). Enteric sepsis (ES), characterized by grade 3 or greater diarrhea and grade 4 neutropenia with or without proven bacteremia occurred in 22 patients treated with FLOX, versus 8 in those treated with FL (P = .01). Patients >60 years were at higher risk for BWI after treatment with FLOX (6.7%) versus treatment with FL (2.9%, P < .01). Female patients had a higher incidence of BWI with FLOX (9.1%) than with FL (3.9%, P < .01). Severe gastrointestinal toxicity usually occurred during the third or fourth week on the first cycle of therapy, required hospitalization, and was managed with fluids, antidiarrheals, and antibiotics. There were 5 deaths (0.3%) due to enteropathy, 2 related to ES and 3 related to both BWI and ES. Seventy-one percent of patients resumed treatment with FL after recovery.

CONCLUSIONS.

Patients treated with adjuvant FL should be closely monitored for diarrhea and aggressively managed, especially if oxaliplatin has been added to the regimen. Cancer 2007. © 2007 American Cancer Society.

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