title: A phase II randomized study of topical intrarectal administration of amifostine for the prevention of acute radiation-induced rectal toxicity.
abstract: 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.
authors.affiliation: Department of Radiation Oncology, Aretaieion University Hospital, University of Athens Medical School, Athens, Greece. vkouloul@cc.ece.ntua.gr
authors.forename: Vassilis E
authors.initials: VE
authors.lastname: Kouloulias
authors.forename: John R
authors.initials: JR
authors.lastname: Kouvaris
authors.forename: George
authors.initials: G
authors.lastname: Pissakas
authors.forename: John D
authors.initials: JD
authors.lastname: Kokakis
authors.forename: Christos
authors.initials: C
authors.lastname: Antypas
authors.forename: Elias
authors.initials: E
authors.lastname: Mallas
authors.forename: George
authors.initials: G
authors.lastname: Matsopoulos
authors.forename: Spyros
authors.initials: S
authors.lastname: Michopoulos
authors.forename: Sofoklis-Panagiotis
authors.initials: SP
authors.lastname: Vosdoganis
authors.forename: Athanasios
authors.initials: A
authors.lastname: Kostakopoulos
authors.forename: Lambros J
authors.initials: LJ
authors.lastname: Vlahos
mesh_terms: 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
chemical_list: D011837:Radiation-Protective Agents; D004999:Amifostine