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: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota. Electronic address: miller.robert@mayo.edu.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Miller
authors.affiliation: Rapid City Regional Oncology Group, Rapid City, South Dakota.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Petereit
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
authors.forename: Jeff A
authors.initials: JA
authors.lastname: Sloan
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
authors.forename: Heshan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
authors.forename: James A
authors.initials: JA
authors.lastname: Martenson
authors.affiliation: Upstate Carolina Community Clinical Oncology Program, Spartanburg, South Carolina.
authors.forename: James D
authors.initials: JD
authors.lastname: Bearden
authors.affiliation: Carle Cancer Center CCOP, Urbana, Illinois.
authors.forename: Ronald
authors.initials: R
authors.lastname: Sapiente
authors.affiliation: Altru Health Systems, Grand Forks, North Dakota.
authors.forename: Grant R
authors.initials: GR
authors.lastname: Seeger
authors.affiliation: Toledo Community Hospital Oncology Program CCOP, Toledo, Ohio.
authors.forename: Rex B
authors.initials: RB
authors.lastname: Mowat
authors.affiliation: University of New Mexico, Albuquerque, New Mexico.
authors.forename: Ben
authors.initials: B
authors.lastname: Liem
authors.affiliation: Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Iott
authors.affiliation: Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Loprinzi
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003967:Diarrhea / Q000517:prevention & control*; D004311:Double-Blind Method; D004751:Enteritis / Q000517:prevention & control; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010388:Pelvis / Q000528:radiation effects*; D011832:Radiation Injuries / Q000517:prevention & control*; D012460:Sulfasalazine / Q000627:therapeutic use*
chemical_list: D012460:Sulfasalazine