A phase II randomized study of topical intrarectal administration of amifostine for the prevention of acute radiation-induced rectal toxicity.
OBJECTIVE
To investigate the cytoprotective effect of intrarectal amifostine administration on acute radiation-induced rectal toxicity.


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.


CONCLUSIONS
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.
Kouloulias
Vassilis E
VE
Department of Radiation Oncology, Aretaieion University Hospital, University of Athens Medical School, Athens, Greece. vkouloul@cc.ece.ntua.gr
Kouvaris
John R
JR
Pissakas
George
G
Kokakis
John D
JD
Antypas
Christos
C
Mallas
Elias
E
Matsopoulos
George
G
Michopoulos
Spyros
S
Vosdoganis
Sofoklis-Panagiotis
SP
Kostakopoulos
Athanasios
A
Vlahos
Lambros J
LJ
D000285:Administration, Rectal; D000287:Administration, Topical; D000368:Aged; D004999:Amifostine / Q000008:administration & dosage* / Q000009:adverse effects; D005240:Feasibility Studies; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D011832:Radiation Injuries / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D011878:Radiotherapy / Q000009:adverse effects* / Q000379:methods; D012002:Rectal Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D012007:Rectum / Q000293:injuries* / Q000473:pathology / Q000528:radiation effects*; D016896:Treatment Outcome
D011837:Radiation-Protective Agents; D004999:Amifostine