Effects of Gefitinib on Radiation-induced Lung Injury in Mice

Clinical studies have demonstrated that gefitinib, an epidermal growth factor receptor inhibitor, is an effective treatment for some patients with advanced non-small cell lung cancer and is generally well-tolerated. However, several reports have also suggested that gefitinib is associated with acute lung injury and subsequent fibrosis. One hypothesis is that gefitinib exacerbates lung injury induced by radiation therapy. It is important to confirm the safety of gefitinib in radiotherapy for patients with lung cancer. In this preclinical study we aimed to clarify the effect of gefitinib on thoracic radiotherapy. Six-week-old female C57BL/6 mice were immobilized in a plastic frame, and the thorax was irradiated once with a dose of 12 Gy on day 0. Gefitinib (20, 90 and 200 mg/kg/day) was administered on days 0 to 5 (acute phase) or days 14 to 19 (late phase) postirradiation. Thoracic irradiation induced lung injury and subsequent fibrosis 5 months later. Gefitinib, administered in the acute phase, had no effect on lung fibrosis or collagen levels induced by irradiation. A high dose of gefitinib (200 mg/kg/day) administered during the late phase significantly reduced fibrosis scores and collagen levels. These results suggest that gefitinib does not exacerbate radiation-induced lung injury and fibrosis in this strain of mice. Therefore, thoracic irradiation is unlikely to be a risk factor for lung injury associated with gefitinib treatment.