Pulmonary Toxicity Associated With the Treatment of Non-Small Cell Lung Cancer and the Effects of Cytoprotective Strategies

Concurrent chemoradiation regimens for the treatment of non-small cell lung cancer have resulted in improved treatment outcomes. However, they are also more toxic. Acute esophagitis and pneumonitis are experienced by a large number of treated patients. Cytoprotective agents are used to reduce treatment-related toxicity. The cytoprotectant amifostine has been shown to reduce some of the toxicity associated with concurrent chemoradiation. Clinical studies of its role in reducing esophagitis and radiation pneumonitis are discussed. Lung irradiation also leads to a reduction in lung diffusion capacity (DLCO). The magnitude of this reduction is related to the volume of lung irradiated as well as to the use and timing of chemotherapy. Concurrent chemoradiation regimens result in a larger reduction in DLCO than radiation alone. Small changes in DLCO can be detected with sensitive pulmonary function tests, but are subclinical. Larger reductions in DLCO correlate with significant clinical symptoms. Preliminary data show that amifostine can significantly decrease the treatment-related reduction in DLCO associated with concurrent chemoradiation (42% v 24%; P = .004). Additional studies are being designed to verify these results and to further define the evolving role of cytoprotection in cancer care.