The use of sulfasalazine during and after pelvic radiation may increase risk for diarrhea, according to the results of a randomized phase 3 study presented at the ASTRO Annual Meeting.
A prior phase 3 trial suggested sulfasalazine (Azulfidine, Watson Laboratories) — an oral tablet used to treat bowel inflammation — decreased enteritis, or inflammation of the intestinal tract. Evidence-based guidelines have recommended sulfasalazine as a prophylactic agent to reduce radiation therapy-associated enteritis, according to background information provided by researchers.
The current double bind, placebo-controlled trial — designed to provide confirmatory evidence with regard to sulfasalazine’s benefit during pelvic radiation therapy — included 87 patients who received pelvic radiation at 24 centers between 2011 and 2013.
Each patient received 1,000 mg sulfasalazine twice daily or placebo during pelvic radiation and for 4 weeks thereafter.
Maximal severity of diarrhea during and up to 6 weeks after radiation served as the primary endpoint.
Severity and duration of diarrhea, rectal bleeding, abdominal cramping, tenesmus and constipation were assessed weekly. Patients completed a bowel function questionnaire weekly during radiation and at 6 weeks, 12 months and 24 months thereafter.
An interim analysis included 78 evaluable patients.
Incidence of grade 1 (38% vs. 29%) and grade 2 (33% vs. 18%) diarrhea was higher in the placebo group. However, results showed grade ≥3 diarrhea occurred in 29% of patients assigned to sulfasalazine vs. 11% of patients assigned placebo (P=.037).
“A futility analysis revealed that continuation of the trial would be highly unlikely to yield a positive result,” researchers wrote.
The Alliance Data and Safety Monitoring Board halted study treatment on May 13, 2013.
“For the prevention of radiotherapy-related diarrhea, we now know that sulfasalazine will not benefit patients,” researcher Robert C. Miller, MD, MS, professor of radiation oncology at Mayo Medical School and vice chairman of research of radiation and oncology at Mayo Clinic in Rochester, Minn., said in a press release. “This trial clearly illustrates the necessity for large, phase 3, randomized controlled trials to understand which drugs and therapies will relieve the more negative side effects for patients receiving radiation therapy.”
For more information:
Miller RC. Abstract #LBA2. Presented at: 2013 ASTRO Annual Meeting; Sept. 22-25, 2013; Atlanta.
: One researcher reports stock ownership in Tekcapital Limited.