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Title: N08C9 (Alliance): A Phase 3 Randomized Study of Sulfasalazine Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy

Abstract

Purpose: To provide confirmatory evidence on the use of sulfasalazine to reduce enteritis during pelvic radiation therapy (RT), following 2 prior single-institution trials suggestive that benefit existed. Methods and Materials: A multi-institution, randomized, double-blind, placebo-controlled phase 3 trial was designed to assess the efficacy of sulfasalazine versus placebo in the treatment of RT-related enteritis during RT including the posterior pelvis (45.0-53.5 Gy) and conducted through a multicenter national cooperative research alliance. Patients received 1000 mg of sulfasalazine or placebo orally twice daily during and for 4 weeks after RT. The primary endpoint was maximum severity of diarrhea (Common Terminology Criteria for Adverse Events version 4.0). Toxicity and bowel function were assessed by providers through a self-administered bowel function questionnaire taken weekly during RT and for 6 weeks afterward. Results: Eighty-seven patients were enrolled in the trial between April 29, 2011, and May 13, 2013, with evenly distributed baseline factors. At the time of a planned interim toxicity analysis, more patients with grade ≥3 diarrhea received sulfasalazine than received placebo (29% vs 11%, P=.04). A futility analysis showed that trial continuation would be unlikely to yield a positive result, and a research board recommended halting study treatment. Final analysis of the primary endpoint showed no significantmore » difference in maximum diarrhea severity between the sulfasalazine and placebo arms (P=.41). Conclusions: Sulfasalazine does not reduce enteritis during pelvic RT and may be associated with a higher risk of adverse events than placebo. This trial illustrates the importance of confirmatory phase 3 trials in the evaluation of symptom-control agents.« less

Authors:
 [1];  [2]; ;  [3];  [1];  [4];  [5];  [6];  [7];  [8];  [1];  [9]
  1. Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States)
  2. Rapid City Regional Oncology Group, Rapid City, South Dakota (United States)
  3. Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota (United States)
  4. Upstate Carolina Community Clinical Oncology Program, Spartanburg, South Carolina (United States)
  5. Carle Cancer Center CCOP, Urbana, Illinois (United States)
  6. Altru Health Systems, Grand Forks, North Dakota (United States)
  7. Toledo Community Hospital Oncology Program CCOP, Toledo, Ohio (United States)
  8. University of New Mexico, Albuquerque, New Mexico (United States)
  9. Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota (United States)
Publication Date:
OSTI Identifier:
22648732
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 95; Journal Issue: 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; DIARRHEA; ENTERITIS; GY RANGE 10-100; PATIENTS; RADIATION HAZARDS; RADIOTHERAPY; SIDE EFFECTS

Citation Formats

Miller, Robert C., E-mail: miller.robert@mayo.edu, Petereit, Daniel G., Sloan, Jeff A., Liu, Heshan, Martenson, James A., Bearden, James D., Sapiente, Ronald, Seeger, Grant R., Mowat, Rex B., Liem, Ben, Iott, Matthew J., and Loprinzi, Charles L. N08C9 (Alliance): A Phase 3 Randomized Study of Sulfasalazine Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.01.063.
Miller, Robert C., E-mail: miller.robert@mayo.edu, Petereit, Daniel G., Sloan, Jeff A., Liu, Heshan, Martenson, James A., Bearden, James D., Sapiente, Ronald, Seeger, Grant R., Mowat, Rex B., Liem, Ben, Iott, Matthew J., & Loprinzi, Charles L. N08C9 (Alliance): A Phase 3 Randomized Study of Sulfasalazine Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy. United States. doi:10.1016/J.IJROBP.2016.01.063.
Miller, Robert C., E-mail: miller.robert@mayo.edu, Petereit, Daniel G., Sloan, Jeff A., Liu, Heshan, Martenson, James A., Bearden, James D., Sapiente, Ronald, Seeger, Grant R., Mowat, Rex B., Liem, Ben, Iott, Matthew J., and Loprinzi, Charles L. Fri . "N08C9 (Alliance): A Phase 3 Randomized Study of Sulfasalazine Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy". United States. doi:10.1016/J.IJROBP.2016.01.063.
@article{osti_22648732,
title = {N08C9 (Alliance): A Phase 3 Randomized Study of Sulfasalazine Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy},
author = {Miller, Robert C., E-mail: miller.robert@mayo.edu and Petereit, Daniel G. and Sloan, Jeff A. and Liu, Heshan and Martenson, James A. and Bearden, James D. and Sapiente, Ronald and Seeger, Grant R. and Mowat, Rex B. and Liem, Ben and Iott, Matthew J. and Loprinzi, Charles L.},
abstractNote = {Purpose: To provide confirmatory evidence on the use of sulfasalazine to reduce enteritis during pelvic radiation therapy (RT), following 2 prior single-institution trials suggestive that benefit existed. Methods and Materials: A multi-institution, randomized, double-blind, placebo-controlled phase 3 trial was designed to assess the efficacy of sulfasalazine versus placebo in the treatment of RT-related enteritis during RT including the posterior pelvis (45.0-53.5 Gy) and conducted through a multicenter national cooperative research alliance. Patients received 1000 mg of sulfasalazine or placebo orally twice daily during and for 4 weeks after RT. The primary endpoint was maximum severity of diarrhea (Common Terminology Criteria for Adverse Events version 4.0). Toxicity and bowel function were assessed by providers through a self-administered bowel function questionnaire taken weekly during RT and for 6 weeks afterward. Results: Eighty-seven patients were enrolled in the trial between April 29, 2011, and May 13, 2013, with evenly distributed baseline factors. At the time of a planned interim toxicity analysis, more patients with grade ≥3 diarrhea received sulfasalazine than received placebo (29% vs 11%, P=.04). A futility analysis showed that trial continuation would be unlikely to yield a positive result, and a research board recommended halting study treatment. Final analysis of the primary endpoint showed no significant difference in maximum diarrhea severity between the sulfasalazine and placebo arms (P=.41). Conclusions: Sulfasalazine does not reduce enteritis during pelvic RT and may be associated with a higher risk of adverse events than placebo. This trial illustrates the importance of confirmatory phase 3 trials in the evaluation of symptom-control agents.},
doi = {10.1016/J.IJROBP.2016.01.063},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 95,
place = {United States},
year = {Fri Jul 15 00:00:00 EDT 2016},
month = {Fri Jul 15 00:00:00 EDT 2016}
}