Phase II trial of subcutaneous amifostine in patients undergoing radiation therapy for head and neck cancer

Abstract

The availability of subcutaneously (SC) administered amifostine may present an advantage for radioprotectant therapy in head and neck cancer patients. In a randomized phase II trial comparing SC amifostine versus no amifostine in 140 patients undergoing radiation therapy for head and neck, thoracic, or pelvic cancers, amifostine treatment was associated with reductions in mucosal toxicity and delays in radiation therapy among the 19 patients with head and neck cancer, as well as in the thoracic and pelvic cancer groups. A phase II trial of SC amifostine in head and neck cancer was performed in a patient population (n = 54) similar to that studied in a phase III trial of intravenous amifostine to allow comparisons of outcomes. Acute xerostomia grade 2 occurred in 56% with SC amifostine and 51% with intravenous amifostine (78% in the no-amifostine group in phase III trial), with median time to onset being 40 days and 45 days, respectively (30 days with no amifostine), and cumulative radiation dose to onset being 58 Gy and 60 Gy (42 Gy with no amifostine), respectively. Amifostine SC was well tolerated, with three quarters of patients receiving > or =75% of the planned dose. Nausea, vomiting, and hypotension were less severe with SC amifostine, but cutaneous toxicity was more frequent. The reduction in radiation therapy-induced acute xerostomia with SC amifostine is similar to that with intravenous amifostine in patients with head and neck cancer. If cutaneous toxicity is judged an acceptable risk, SC amifostine may represent a second, more convenient option for treating physicians.