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 N0 M0 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 intrarectally 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.