Does Lapatinib Increase Pulmonary Toxicity when Concurrently Used with Radiation Therapy? An Experimental Study with Wistar-Albino Rats

Abstract

Lapatinib is an oral receptor tyrosine kinase inhibitor which has shown activity in the treatment of metastatic breast cancer. There is no data regarding the side effects of combination of radiotherapy and Lapatinib. 40 female Wistar-albino rats (WAR) were divided into 4 groups

G1 did not receive any treatment, G2 received radiotherapy to whole thoracic region, G3 received Lapatinib without radiotherapy, G4 received Lapatinib with radiotherapy. A total dose of 30 Gy in 10 fractions was given to both lungs. Lapatinib equivalent to 1500 mg/day were calculated according to the mean weight of rats, orally administrated. A comparative analysis was performed by scoring the pulmonary injury between 0 and 3 according to the infiltration of inflammatory cells into the alveolar spaces, alveolar wall thickening and architectural deformation across the entire lung section. In G2 inflammatory cell infiltration, fibrosis with damage to lung structure andformation of small fibrous masses were observed. Alveolar septa were significantly thicker than G1 (p <= 0.001), which revealed totally normal pulmonary structure. G3 showed minimal alveolar septal thickening and infiltration of inflammatory cells into the alveolar spaces which was not significantly different than G1. Histopathological findings in G4 were similar to those in G2 and statistically different when compared with the G1 and G3 (p <= 0.001). In this experimental study it has been shown that addition of Lapatinib to radiation did not increase RIPF in rats.