Subcutaneous administration of amifostine during fractionated radiotherapy: A randomized phase II study

Purpose: Amifostine (WR-2721) is an impotant 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 ifs simplicity, presents multiple advantages over the intravenous route wh en amifostine is used during fractionated radiotherapy. Patients and Methods: Sixty patients with thoracic, 40 with head and neck, and 40 wish pelvic tumors who were undergoing radical radiotherapy were enr olled onto ct randomized phase II trial to assess the feasibility, toleranc e, and cytoprotective efficacy of amifostine administered subcutaneously, A flat dose of amifostine 500 mg, diluted in 2.5 mL of normal saline, was in jected subcutaneously 20 minutes before each radiotherapy fraction. Results: The subcutaneous amifostine regimen wets well tolerated by 85% of patients. In approximately 5% of patients, amifostine therapy was interrupt ed due to cumulative asthenia, and in 10%, due to a fever/rash reaction. Hy potension was never noted, whereas nausea was frequent. A significant reduc tion of pharyngeal, esophageal, and rectal mucositis was noted in the amifo stine arm (P < .04). The delays in radiotherapy because of grade 3 mucositi s were significantly longer in the group of patients treated with radiother apy alone (P < .04). Amifostine significantly reduced the incidence of acut e perineal skin and bladder toxicity (P < .0006). Conclusion: Subcutaneous administration of amifostine is well tolerated, ef fectively reduces radiotherapy's early toxicity, and prevents delays in rad iotherapy. The subcutaneous route is much simpler and saves time compared w ith the intravenous route of administration and can be safely and effective ly applied in the daily, busy radiotherapy practice. J Clin Oncol 18:2226-2 233. (C) 2000 by American Society of Clinical Oncology.