Open label multicenter trial of subcutaneous amifostine (Ethyol) in the prevention of radiation induced esophagitis and pneumonitis in patients with measurable, unresectable non-small cell lung cancer.

While concurrent delivery of chemotherapy and radiotherapy (RT) has a synergistic effect on tumor control and improves the median and overall survival in patients with locally advanced non-small cell lung cancer, appreciable acute and late morbidity occur to the esophagus and the lung during treatment (ie, acute radiation esophagitis, pulmonary toxicity). Emerging evidence suggests that the volume of normal lung exposed to certain threshold doses of RT might predict for the incidence of pneumonitis. Clinical data also indicate that amifostine (Ethyol; Medimmune Inc, Gaithersburg, MD), an organic thiophosphate, acts as a selective cytoprotective agent for normal tissues against the toxicities of chemotherapy and RT. Moreover, preclinical and clinical data suggest that subcutaneous administration of amifostine may be better tolerated with similar efficacy to that of the intravenous route. We are conducting an open-label trial that is accruing patients with locally advanced non-small cell lung cancer, who will receive concurrent chemoradiotherapy (cisplatin/etoposide or carboplatin/paclitaxel plus RT delivered using 3-dimensional conformal radiotherapy treatment planning) and amifostine 500 mg before RT. Incidence and severity of acute radiation esophagitis, acute radiation pneumonitis, chronic radiation pneumonitis, and changes in pulmonary function will be recorded, as will elements of the RT treatment planning (eg, dose volume histogram data for the lung and esophagus). Pre- and post-therapy pulmonary function is a primary endpoint, and others include general safety assessments of subcutaneous amifostine administration.