Amifostine in simultaneous radiochemotherapy for head and neck cancer

Objective: The efficacy of the selective cytoprotective agent amifostine in patients with stage III or IV head and neck cancer treated with concurrent carboplatin and radiation therapy was evaluated in a randomized phase II trial. Patients and Methods: Thirty-nine patients with squamous cell carcinomas of the head and neck received adjunctive or primary radiotherapy (5 days per week with daily fractions of 2 Gy, up to a total dose of 60 Gy) in conjunction with carboplating (70 m/m(2)) on days 1-5 and days 21-25. AU patients received radiation, encompassing at least 75 % of the major salivary glands. The patients were randomized to receive radiation and carboplatin therapy (RCT) alone or RCT preceded by rapid infusion of amifostine (500 rug) on the days carboplatin was administered. Results and Conclusion: Patients treated with amifostine had significant reductions in mucositis (p = 0.0001) and xerostomia (p = 0.0001) relative to patients treated with RCT alone. None of the 25 patients treated with amifostine but 12 of 14 patients (86%) treated with RCT alone developed grade 3 or 4 mucositis. Additionally, patients in the amifostine plus RCT arm had significantly less severe bone marrow toxicity from carboplatin, thrombocytopenia (p = 0.001) and leukopenia (p = 0.001), relative to patients treated with RCT alone. Of 75 patients in the amifostine arm, 18 (72%) exhibited a complete response and 6 (24%) a partial response as compared with 6 (43%) complete responses and 6 (43%) partial responses in the RCT-alone arm. Selective cytoprotection with amifostine offers Substantial protection against the dose-limiting toxicities of RCT for patients with head and neck cancer with no reduction in antitumor effect.