title: 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.
authors.affiliation: Department of Radiation Oncology, Cerrahpasa Medical School, Istanbul University, 34098, Cerrahpasa, Istanbul, Turkey. nuranbese@superonline.com
authors.forename: N S
authors.initials: NS
authors.lastname: Bese
authors.forename: C
authors.initials: C
authors.lastname: Umay
authors.forename: S
authors.initials: S
authors.lastname: Serdengecti
authors.forename: N
authors.initials: N
authors.lastname: Kepil
authors.forename: N
authors.initials: N
authors.lastname: Sut
authors.forename: T
authors.initials: T
authors.lastname: Altug
authors.forename: A
authors.initials: A
authors.lastname: Ober
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D005260:Female; D011379:Prognosis; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D017208:Rats, Wistar; D000068878:Trastuzumab; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C000715649:Tpt1 protein, rat; D000090324:Tumor Protein, Translationally-Controlled 1; D000068878:Trastuzumab