Phase III randomized trial of amifostine as a radioprotector in head and neck cancer

Purpose: Radiotherapy for head and neck cancer causes acute and chronic xer ostomia and acute mucositis. Amifositine and its active metabolite, WR-1065 , accumulate with high concentrations in the salivary glands. This randomiz ed trial evaluated whether amifostine could ameliorate these side effects w ithout compromising the effectiveness of radiotherapy in these patients. Patients and Methods: Patients with previously untreated head and neck squa mous cell carcinoma were eligible. Primary end points included the incidenc e of grade greater than or equal to 2 acute xerostomia, grade greater than or equal to 3 acute mucositis, and grade greater than or equal to 2 late xe rostomia and were based on the worst toxicity reported. Amifostine was admi nistered (200 mg/m(2) intravenous) daily 15 to 30 minutes before irradiatio n. Radiotherapy was given once daily (1.8 to 2.0 Gy) to doses of 50 to 70 G y. Whole saliva production was quantitated preradiotherapy and regularly du ring follow-up. Patients evaluated their symptoms through a questionnaire d uring and after treatment. Local-regional control was the primary antitumor efficacy end point. Results: Nausea, vomiting, hypotension, and allergic reactions were the mos t common side effects. Fifty-three percent of the patients receiving amifos tine had at least one episode of nausea and/or vomiting, but it only occurr ed with 233 (5%) of 4,314 doses. Amifostine reduced grade greater than or e qual to 2 acute xerostomia from 78% to 51% (P <.0001) and chronic xerostomi a grade greater than or equal to 2 from 57% to 34% (P =.002). Median saliva production was greater with amifostine (0.26 g v 0.10 g, P =.04). Amifosti ne did not reduce mucositis. With and without amifostine, 2-year local-regi onal control, disease-free survival, and overall survival were 58% versus 6 3%, 53% versus 57% and 71% versus 66%, respectively. Conclusion: Amifostine reduced acute and chronic xerostomia. Antitumor trea tment efficacy was preserved. J Clin Oncol 18:3339-3345, (C) 2000 by Americ an Society of Clinical Oncology.