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

Abstract

Purpose/Objectives

To provide confirmatory evidence in use of sulfasalazine to reduce enteritis during pelvic radiotherapy (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 vs placebo in treatment of RT-related enteritis during RT including the posterior pelvis 45.0-53.0 Gy) and conducted through a multi-center national cooperative research alliance Patients received 1,000 mg sulfasalazine or placebo orally twice daily during and for 4 weeks after RT. Primary end point was maximal severity of diarrhea (Common Terminology Criteria for Adverse Events version 4.0). Toxicity and bowel function were assessed by providers through 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 diarrhea grade ≥3 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 end point showed no significant difference in maximum diarrhea severity between sulfasalazine and placebo arms ( P=.41).

Conclusions

Sulfasalazine does not reduce enteritis during pelvic RT and may be associated with higher risk of adverse events than placebo. This trial illustrates the importance of confirmatory Phase 3 trials in the evaluation of symptom control agents.