title: Phase II multicenter randomized study of amifostine for prevention of acute radiation rectal toxicity: topical intrarectal versus subcutaneous application.
abstract: OBJECTIVE
  To investigate the cytoprotective effect of subcutaneous vs. intrarectal administration of amifostine against acute radiation toxicity.
  
  
  METHODS
  Patients were randomized to receive amifostine either intrarectally (Group A, n = 27) or a 500-mg flat dose subcutaneously (Group B, n = 26) before irradiation. Therapy was delivered using a four-field technique with three-dimensional conformal planning. In Group A, 1,500 mg of amifostine was administered intrarectally as an aqueous solution in 40 mL of enema. Two different toxicity scales were used: the European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group (RTOG) rectal and urologic toxicity criteria and the Subjective-RectoSigmoid 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 radiotherapy completion. The area under the curve for the time course of mucositis (RTOG criteria) during irradiation represented the mucositis index.
  
  
  RESULTS
  Intrarectal amifostine was feasible and well tolerated without any systemic or local side effects. According to the RTOG toxicity scale, Group A had superior results with a significantly lower incidence of Grades I-II rectal radiation morbidity (11% vs. 42%, p = 0.04) but inferior results concerning urinary toxicity (48% vs. 15%, p = 0.03). The mean rectal mucositis index and Subjective-RectoSigmoid score were significantly lower in Group A (0.44 vs. 2.45 [p = 0.015] and 3.9 vs. 6.0 [p = 0.01], respectively), and the mean urinary mucositis index was lower in Group B (2.39 vs. 0.34, p < 0.028).
  
  
  CONCLUSIONS
  Intrarectal administration of amifostine (1,500 mg) seemed to have a cytoprotective efficacy in acute radiation rectal mucositis but was inferior to subcutaneous administration in terms of urinary toxicity. Additional randomized studies are needed for definitive decisions concerning the cytoprotection of pelvic irradiated areas.
authors.affiliation: Department of Radiation Oncology, Aretaieion University Hospital, Medical School of Athens, 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: Elias
authors.initials: E
authors.lastname: Mallas
authors.forename: Christos
authors.initials: C
authors.lastname: Antypas
authors.forename: John D
authors.initials: JD
authors.lastname: Kokakis
authors.forename: George
authors.initials: G
authors.lastname: Matsopoulos
authors.forename: Spyros
authors.initials: S
authors.lastname: Michopoulos
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Mystakidou
authors.forename: Lambros J
authors.initials: LJ
authors.lastname: Vlahos
mesh_terms: D000285:Administration, Rectal; D004999:Amifostine / Q000008:administration & dosage*; D005260:Female; D005833:Genital Neoplasms, Female / Q000532:radiotherapy; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D011471:Prostatic Neoplasms / Q000532:radiotherapy; D011832:Radiation Injuries / Q000517:prevention & control*; D011837:Radiation-Protective Agents; D020266:Radiotherapy, Conformal; D012007:Rectum / Q000187:drug effects / Q000528:radiation effects*; D018709:Statistics, Nonparametric; D001743:Urinary Bladder / Q000187:drug effects / Q000528:radiation effects
chemical_list: D011837:Radiation-Protective Agents; D004999:Amifostine