Randomized phase II exploratory study of prophylactic amifostine in cancer patients who receive radical radiotherapy to the pelvis

Abstract

BackgroundThis study aimed to investigate the efficacy of prophylactic amifostine in reducing the risk of severe radiation colitis in cancer patients receiving radical radiotherapy to the pelvis.MethodsPatients with pelvic tumours referred for radical radiotherapy who consented participation in this trial, were randomly assigned to receive daily amifostine (A) (subcutaneously, 500 mg flat dose) before radiotherapy or radiotherapy alone (R). Sigmoidoscopy and blinded biopsies were scheduled to conduct prior to initiation and following completion of radiotherapy and again 6 to 9 months later. Radiation colitis was assessed by clinical, endoscopic and histolopathological criteria.ResultsA total 44 patients were enrolled in this trial, the majority with rectal (20 patients) and cervical cancer (12 patients) and were assigned 23 in R arm and 21 in the A arm. In total 119 sigmoidoscopies were performed and 18 patients (18/44, 40.9%) were diagnosed with radiation colitis (15 grade 1 and 2, and 3 grade 3 and 4). Of them, 6 patients belonged to the A group (6/21, 28.6%) and 12 to the R group (12/23, 52.2%). Acute and grade IV radiation colitis was only developed in four patients (17.4%) in the R group. Amifostine side effects were mild. Amifostine treated patients were less likely to develop histologically detectable mucosal lesions, which indicate protection from acute mucosal injury.ConclusionsAmifostine given subcutaneously can lower the risk of acute severe radiation colitis in patients who receive radical radiotherapy to pelvic tumors.

The histopathological comparison of L-carnitine with amifostine for protective efficacy on radiation-induced acute small intestinal toxicity

“…They revealed that acute radiation colitis and grade IV radiation colitis did not occur in the amifostine arm, but in 17.4% of patients who did not receive amifostine prophylaxis (P = 0.05). [29] Similar results showing the radioprotector activity of amifostine was obtained in the present study. It was significantly protective against both vascular and degenerative radiation induced damage on small intestine tissue.…”

Dose Escalation of Amifostine for Radioprotection During Pelvic Accelerated Radiotherapy

“…The significant number of studies indicating the cytoprotective efficacy of amifostine on pelvic tissues led international committees to suggest the eventual usage of the drug for the prevention of intestinal toxicities during radiotherapy for rectal cancer. 15,16 In the current study, we report the effect of escalated amifostine dose on pelvic tissue protection in patients with pelvic carcinomas recruited in prospective protocols applying HypoARC. 12 A dose of 340 mg/m 2 /d was able to significantly reduce the rate of late radiation sequel from pelvic tissues.…”

The Protective Effect of Amifostine on Radiation-Induced Proctitis: Systemic Versus Topical Application

“…In another study by Ito et al (25), the authors concluded that WR-2721 is indeed effective in protection against late damage from large single doses of radiation to the rectum as measured histologically and also improves the long-term survival of the mice, although the target cells for this damage are not known. Recently, Katsanos et al (26) stated that amifostine given subcutaneously can lower the risk of acute severe radiation colitis in a randomised phase II exploratory clinical trial. They revealed that acute radiation colitis and grade IV radiation colitis did not occur in the amifostine arm but developed in 17.4% of patients who did not receive amifostine prophylaxis (p=0.05).…”