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Journal of Clinical Oncology, Vol 18, Issue 19 (October), 2000: 3339-3345
© 2000 American Society for Clinical Oncology

Phase III Randomized Trial of Amifostine as a Radioprotector in Head and Neck Cancer

By David M. Brizel, Todd H. Wasserman, Michael Henke, Vratislav Strnad, Volkar Rudat, Alain Monnier, Francois Eschwege, Jay Zhang, Lesley Russell, Wolfgang Oster, Rolf Sauer

From the Department of Radiation Oncology, Duke University Medical Center, Durham, NC; Division of Radiation Oncology, Mallinckrodt Institute of Radiology, St. Louis, MO; Clinic of Radiation Oncology, University of Freiburg, Freiburg; Clinic of Radiation Oncology, Erlangen; Clinic of Radiation Oncology, University of Heidelberg, Heidelberg, Germany; CHG Andre Boulloche, Montebeliard; Department of Radiotherapy, Institute Gustave-Roussy, Villejuif Cedex, France; and Medimmune Oncology, Inc, West Conshohocken, PA.

Address reprint requests to David M. Brizel, MD, Department of Radiation Oncology, Box 3085, Duke University Medical Center, Durham, NC 27710; email brizel{at}radonc.duke.edu

PURPOSE: Radiotherapy for head and neck cancer causes acute and chronic xerostomia and acute mucositis. Amifositine and its active metabolite, WR-1065, accumulate with high concentrations in the salivary glands. This randomized trial evaluated whether amifostine could ameliorate these side effects without compromising the effectiveness of radiotherapy in these patients.

PATIENTS AND METHODS: Patients with previously untreated head and neck squamous cell carcinoma were eligible. Primary end points included the incidence of grade >= 2 acute xerostomia, grade >= 3 acute mucositis, and grade >= 2 late xerostomia and were based on the worst toxicity reported. Amifostine was administered (200 mg/m2 intravenous) daily 15 to 30 minutes before irradiation. Radiotherapy was given once daily (1.8 to 2.0 Gy) to doses of 50 to 70 Gy. Whole saliva production was quantitated preradiotherapy and regularly during follow-up. Patients evaluated their symptoms through a questionnaire during and after treatment. Local-regional control was the primary antitumor efficacy end point.

RESULTS: Nausea, vomiting, hypotension, and allergic reactions were the most common side effects. Fifty-three percent of the patients receiving amifostine had at least one episode of nausea and/or vomiting, but it only occurred with 233 (5%) of 4,314 doses. Amifostine reduced grade >= 2 acute xerostomia from 78% to 51% (P < .0001) and chronic xerostomia grade >= 2 from 57% to 34% (P = .002). Median saliva production was greater with amifostine (0.26 g v 0.10 g, P = .04). Amifostine did not reduce mucositis. With and without amifostine, 2-year local-regional control, disease-free survival, and overall survival were 58% versus 63%, 53% versus 57%, and 71% versus 66%, respectively.

CONCLUSION: Amifostine reduced acute and chronic xerostomia. Antitumor treatment efficacy was preserved.




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