A phase III, randomized, double-blind, placebo-controlled, multinational trial of iseganan for the prevention of oral mucositis in patients receiving stomatotoxic chemotherapy (PROMPT-CT trial)

Microfloral invasion and colonization of oral cavity mucosal tissues contribute to the pathophysiology of ulcerative oral mucositis (UOM). Iseganan is an analog of Protegrin-1, a naturally occurring peptide with broad-spectrum microbicidal activity. A randomized, double-blind, placebo-controlled study was conducted to evaluate iseganan in preventing UOM after stomatotoxic therapy. Patients received an oral rinse of iseganan 9 mg or placebo, swished/swallowed 6 times daily, starting with stomatotoxic therapy and continuing for 21-28 days. One hundred sixty three and 160 patients, respectively, were randomized to receive iseganan or placebo. One hundred and two patients (32%) were affected by a drug dispensing error, caused by a flawed computerized allocation system. Among all 323 patients, analyzed according to randomization assignment, 43% and 33% of iseganan and placebo patients, respectively, did not develop UOM {P = 0.067}. On an 11-point scale, iseganan patients experienced less mouth pain (3.0 and 3.8 {P = 0.041}), throat pain (3.8 and 4.6 {P = 0.048}), and difficulty swallowing (3.9 and 4.7 {P = 0.074}), compared to placebo patients. On the 5-point NCI CTC scale, iseganan patients experienced lower stomatitis scores (1.6 and 2.0 {P = 0.013}). Iseganan was well tolerated; no systemic absorption was detected. Iseganan is safe and may be effective in reducing UOM and its clinical sequelae.