Prevention of acute radiation-induced proctosigmoiditis by balsalazide: a randomized, double-blind, placebo controlled trial in prostate cancer patients.

PURPOSE: A common complication of pelvic radiotherapy (RT) is acute radiation-induced proctosigmoiditis (RIPS), for which a multitude of therapies have been tried. The 5-aminosalicylates (5-ASA), which are traditionally used to treat inflammatory bowel disease, have been tested; however, all but one prior randomized attempt to limit or prevent RIPS with 5-ASA-type agents have failed. We sought to evaluate balsalazide, a new 5-ASA drug, for its potential to prevent or limit RIPS in patients undergoing RT for carcinoma of the prostate, as a representative sample of pelvic RT patients. Balsalazide has a unique delivery system in that 99% of ingested drug is delivered to and activated in the colon, a higher yield than all other oral agents currently available in this class. Furthermore, it lacks the antigenic sulfa moiety present in sulfasalazine, the only other 5-ASA with demonstrated benefit in this setting. Thus, it was deemed an ideal candidate for preventing or limiting RIPS. METHODS AND MATERIALS: Eligible patients included prostate cancer patients, American Joint Committee on Cancer Stage T1-3, M0 being treated with external beam radiotherapy in the University of Kentucky Department of Radiation Medicine. Between January 1, 2003 and July 1, 2004, 27 eligible patients were enrolled in the study. Patients were administered 2250 mg of balsalazide or an identical-appearing placebo twice daily beginning 5 days before RT and continuing for 2 weeks after completion. Toxicities were graded weekly according to National Cancer Institute Common Toxicity Criteria v. 2.0 for each of the following: proctitis, diarrhea, dysuria, weight loss, fatigue, nausea, and vomiting. A symptom index was formulated for each toxicity consisting of the toxicity's numeric grade multiplied by the number of days it was experienced, and summed for each grade experienced throughout the course of RT.
RESULTS: With the exception of nausea or vomiting, seen in 3 patients on balsalazide and 2 on placebo, all toxicities were appreciably lower in patients taking balsalazide. Proctitis was prevented most significantly with a mean proctitis index of 35.3 in balsalazide patients and 74.1 in placebo patients (p = 0.04). Placebo patients lost an average of 2.7 pounds, whereas balsalazide patients on average gained weight. Unexpectedly, dysuria was also lower in balsalazide-treated patients.
CONCLUSIONS: Balsalazide is a new-generation 5-ASA drug that yields a high concentration of active drug to the distal colon. Results of this pilot study suggest that it is able to prevent or reduce symptoms of RIPS in patients undergoing RT for prostate cancer. We feel that these results justify the formation of a cooperative group trial to assess its efficacy in a multi-institutional setting.

RCT Entities:   Population Interventions Outcomes