title: Subcutaneous administration of amifostine during fractionated radiotherapy: a randomized phase II study.
abstract: OBJECTIVE
  Amifostine (WR-2721) is an important cytoprotective agent. Although intravenous administration is the standard route, pharmacokinetic studies have shown acceptable plasma levels of the active metabolite of amifostine (WR-1605) after subcutaneous administration. The subcutaneous route, due to its simplicity, presents multiple advantages over the intravenous route when amifostine is used during fractionated radiotherapy.
  
  
  METHODS
  Sixty patients with thoracic, 40 with head and neck, and 40 with pelvic tumors who were undergoing radical radiotherapy were enrolled onto a randomized phase II trial to assess the feasibility, tolerance, and cytoprotective efficacy of amifostine administered subcutaneously. A flat dose of amifostine 500 mg, diluted in 2.5 mL of normal saline, was injected subcutaneously 20 minutes before each radiotherapy fraction.
  
  
  RESULTS
  The subcutaneous amifostine regimen was well tolerated by 85% of patients. In approximately 5% of patients, amifostine therapy was interrupted due to cumulative asthenia, and in 10%, due to a fever/rash reaction. Hypotension was never noted, whereas nausea was frequent. A significant reduction of pharyngeal, esophageal, and rectal mucositis was noted in the amifostine arm (P <.04). The delays in radiotherapy because of grade 3 mucositis were significantly longer in the group of patients treated with radiotherapy alone (P <.04). Amifostine significantly reduced the incidence of acute perineal skin and bladder toxicity (P <.0006).
  
  
  CONCLUSIONS
  Subcutaneous administration of amifostine is well tolerated, effectively reduces radiotherapy's early toxicity, and prevents delays in radiotherapy. The subcutaneous route is much simpler and saves time compared with the intravenous route of administration and can be safely and effectively applied in the daily, busy radiotherapy practice.
authors.affiliation: Department of Radiotherapy/Oncology and Medical Oncology, University Hospital of Iraklion, Greece. targ@her.fortnight.gr
authors.forename: M I
authors.initials: MI
authors.lastname: Koukourakis
authors.forename: G
authors.initials: G
authors.lastname: Kyrias
authors.forename: S
authors.initials: S
authors.lastname: Kakolyris
authors.forename: C
authors.initials: C
authors.lastname: Kouroussis
authors.forename: C
authors.initials: C
authors.lastname: Frangiadaki
authors.forename: A
authors.initials: A
authors.lastname: Giatromanolaki
authors.forename: G
authors.initials: G
authors.lastname: Retalis
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
mesh_terms: D000008:Abdominal Neoplasms / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D004999:Amifostine / Q000008:administration & dosage* / Q000009:adverse effects; D016009:Chi-Square Distribution; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D007279:Injections, Subcutaneous; D008875:Middle Aged; D011832:Radiation Injuries / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D013899:Thoracic Neoplasms / Q000532:radiotherapy*; D016896:Treatment Outcome
chemical_list: D011837:Radiation-Protective Agents; D004999:Amifostine