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

Abstract

Background: This 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.

Methods: Patients 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.

Results: A 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.

Conclusions: Amifostine given subcutaneously can lower the risk of acute severe radiation colitis in patients who receive radical radiotherapy to pelvic tumors.

Figure 1

A. Congested rectal mucosa with diffuse erythema in a case of grade I radiation colitis (RTOG/EORTC late radiation morbidity scale for large intestine). B. Ulcerated rectal mucosa with diffuse erythema, mucous and intermittent bleeding in a case of grade II radiation colitis (RTOG/EORTC late radiation morbidity scale for large intestine).

Figure 2

Histopathological findings of radiation-induced colitis. A. Acute injury, characterized by ulceration, absence of viable crypts, diffuse infiltration by polymorphonuclear leucocytes, and prominent capillaries lined by plump endothelial cells (H + E × 400). B. Early regenerative changes, characterized by absence of ulceration, considerably less acute inflammation, infiltration by plasma cells and lymphocytes, presence of viable crypts with disarray, absence of cryptitis or acute epithelial damage (H+E × 400). C. Late regenerative changes, characterized by absence of acute inflammation, mild diffuse infiltration by plama cells and lymphocytes, architectural crypt distortion, with reduced crypts, crypt branching and shortening as well as moderate/severe fibrosis of the lamina propria (H + E × 400).

Figure 3

Immunohistochemical expression of active caspase 3 in apoptotic epithelial cells.