A phase II randomized study of topical intrarectal administration of amifostine for the prevention of acute radiation-induced rectal toxicity

Purpose: To investigate the cytoprotective effect of intrarectal amifostine administration on acute radiation-induced rectal toxicity. Patients and Methods: 67 patients with T1b-2 NO MO prostate cancer were randomized to receive amifostine intrarectally (group A, n = 33) or not (group B, n = 34) before irradiation. Therapy was delivered using a four-field technique with three-dimensional conformal planning. In group A, 1,500 mg amifostine was administered intrarectatly as an aqueous solution in a 40-ml enema. Two different toxicity scales were used: EORTC/RTOG rectal and urologic toxicity criteria along with a Subjective-RectoSigmoid (S-RS) scale based on the endoscopic terminology of the World Organization for Digestive Endoscopy. Objective measurements with rectosigmoidoscopy were performed at baseline and 1-2 days after the completion of radiotherapy. The area under curve for the time course of mucositis (RTOG criteria) during irradiation represented the mucositis index (MI). Results: Intrarectal amifostine was feasible and well tolerated without any systemic or Local side effects. According to the RTOG toxicity scale, five out of 33 patients showed grade 1 mucositis in group A versus 15 out of 34 patients with grade 1/2 in group B (p = 0.026). Mean rectal MI was 0.3 +/- 0.1 in group A versus 2.2 +/- 0.4 in group B (p < 0.001), while S-RS score was 3.9 +/- 0.5 in group A versus 6.3 +/- 0.7 in group B (p < 0.001). The incidence of urinary toxicity was the same in both groups. Conclusion: Intrarectal administration of amifostine seems to have a cytoprotective efficacy in acute radiation-induced rectal mucositis. Further randomized studies are needed for definitive therapeutic decisions.