Esophagitis is a major complication of chemoradiation therapy in patients with non-small cell lung cancer, producing significant morbidity and resulting in treatment interruptions. Amifostine at different doses and schedules has been found to reduce frequency or severity of esophagitis in this setting. In the Radiation Therapy Oncology Group 98-01 trial in non-small cell lung cancer patients receiving chemoradiation therapy, amifostine given intravenously four times weekly did not significantly reduce the frequency of grade 3 or 4 esophagitis; however, a significant reduction in severity over time was observed in patient swallowing diaries. The potential benefits of amifostine may have been obscured by inability to provide full amifostine doses due to toxicity associated with infusion, scheduling of doses, and inadequate follow-up to monitor severity of esophagitis over time. These issues are to be addressed in a randomized phase II trial of amifostine given subcutaneously or via intravenous bolus in non-small cell lung cancer patients undergoing chemoradiation treatment.