The impact of trastuzumab on radiation-induced pulmonary fibrosis: results of an experimental study

Abstract

There are no data regarding the late toxicity of trastuzumab (T) administration with radiotherapy (RT). In this experimental study, we aimed to asses if concurrent or sequential administration of T has any impact for the development of radiation-induced pulmonary fibrosis in rats. Fifty-four female Wistar-albino rats were divided into 6 groups. First group of rats (Group 1; concurrent T) had irradiation to whole thoracic region concurrently with T. Second group (Group 2: sequential T-RT) received thoracic irradiation, 1 week after T. Third group (Group 3: sequential RT-T) had thoracic irradiation first and they had T injection 1 week after RT. Fourth group (Group 4: T only) had only T application. Fifth group (Group 5: RT) had only RT. The last group (Group 6: sham) of rats were observed without any application. A single dose of 12 Gy was given to both lungs with an anterior field at 2 cm depth. T dose which was equivalent to 6 mg/kg adult dose was calculated for each rat, and injected by the tail vein. As an end point the extent of pulmonary fibrosis for each field was graded on a scale from 0 (normal lung or minimal fibrous thickening) to 4 (total fibrous obliteration of the field) at histopathological examination. The mean value of fibrosis scores were 1.44, 1.77, 1.75 and 1.62 for Group 1, 2, 3 and 5, respectively, without any statistically significant differences among them (P > 0.05). The mean value of fibrosis scores for Group 4 and 6 were 0.25 and 0.33, respectively (P > 0.05). When the mean value of fibrosis scores of the groups which had RT with or without T, compared with the observation and the T only groups, the difference was significant (P < 0.05) (one-way ANOVA and Tukey HSD post hoc tests) As a conclusion: addition of T to thoracic irradiation either sequentially or concomitantly did not increase radiation-induced pulmonary fibrosis in rats.