Radioprotective effect of amifostine in radiation pneumonitis.

Amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD) is a member of a sulfhydryl-containing class of compounds that protects normal tissue and organs against ionizing radiation damage by scavenging radiation-induced radicals. The goal of this study was to assess the preclinical and clinical data on the protective effect of amifostine in normal organs and tissue. The current literature was reviewed and assessed for progress in the pathogenesis of radiation-induced pulmonary injury. Preclinical and clinical data on the protective effect of amifostine in radiation-induced lung and esophageal injuries were also critically assessed. Significant progress has been made in understanding the pathogenesis of radiation pneumonitis. Preclinical studies have shown strong evidence of the protective effect of amifostine in radiation-induced toxicities in rodents and monkeys. However, available clinical data are not conclusive in showing the protective effect of amifostine in radiation pneumonitis and esophagitis. Amifostine has been well tolerated with a low incidence of toxicities, which included nausea and vomiting (3% to 5%) and transient hypotension during intravenous infusion (7%). Preclinical data are promising for amifostine in protecting thoracic organs from radiation-induced toxicities. Studies measuring the magnitude of gain in tumor control and survival as a result of the enhanced protective effect of amifostine on normal tissue over that of tumor tissue are lacking. Such data would help in designing new approaches to maximize outcome. Additional well-designed phase III studies are necessary to confirm the clinical benefit of amifostine in minimizing radiation- and chemoradiation-related toxicities in patients with lung cancer.