Salivary gland protection by S-2-(3-aminopropylamino)-ethylphosphorothioic acid (amifostine) in high-dose radioiodine treatment:: Results obtained in a rabbit animal model and in a double-blind multi-arm trial

Since differentiated thyroid cancer has an excellent prognosis, reduction of long-term side effects of high-dose radioiodine treatment (HD-RIT), i.e. salivary gland impairment is important. Thus, radioprotective effects of amifostine were studied. Salivary gland function was quantified by scintigraphy both in rabbits and patients. Fifteen rabbits were studied prior to and up to 6 months after HD-RIT applying 2 GBq I-131. Ten animals received 200 mg/kg amifostine prior to HD-RIT, and five sewed as controls. Animals were examined histopathologically. Fifty patients with differentiated thyroid cancer were evaluated prospectively prior to and 3 months after HD-RIT with either 3 or 6 GBq I-131 in a double-blind placebo-controlled study,. Twenty-Jive patients were created with 500 mg/m(2) amifostine intravenously prior to HD-RIT and 25 patients receiving physiological saline solution sewed as controls. Complete ablation of the thyroid was achieved in all rabbits four weeks after HD-RIT. lit control rabbits 6 months after HD-RIT parenchymal function was reduced significantly (p<0.0001) by 75.3+/-5.3 % and 53.6+/-17.4 % in parotid and submandibular glands, respectively In contrast. in amifostine-treated rabbits parenchymal function was not significantly reduced. Histopathologically, marked lipomatosis was observed in control animals but was negligible in amifostine-treated animals. In control patients, salivary gland function was significantly (p<0.001) reduced by 40.2+/-14.1 % and 39.9+/-15.3 % in parotid and submandibular glands, respectively, three months after HD-RIT, and II patients developed xerostomia. In 25 amifostine-treated Patients, salivary gland function was not significantly reduced (p=0.691), and xerostomia did not occur. Thus, parenchymal damage in salivary glands induced by high-dose radioiodine therapy can be reduced significantly by amifostine. This may improve quality of life of patients with differentiated thyroid cancer.