Concomitant trastuzumab with thoracic radiotherapy: a morphological and functional study

Ann Oncol. 2011 May;22(5):1120-1126. doi: 10.1093/annonc/mdq590. Epub 2010 Nov 19.

Abstract

Background: The purpose of this study is to elucidate if there is an additive or supra-additive toxic effects of radiotherapy (RT) and trastuzumab (T) on vascular structures when used concomitantly.

Methods: Female Wistar albino rats were treated with either 8 or 15 Gy of thoracic RT. T was applied i.p. with a dose of 6 mg/kg 2 h before RT. Four rats in each arm were killed at 6th h, 21st and 70th days after irradiation and thoracic aorta of each animal was dissected for electron microscopy. In addition, functional studies for evaluating the relaxation and contraction were carried out 21 days after RT.

Results: Only 15-Gy RT dose groups showed significant difference in terms of functional deterioration as more contraction than the others (P < 0.05) without any difference between RT and RT + T. However, T produced additional deficit in relaxation when added to RT, which was considered near significant (P: 0.0502). Electron microscopy showed endothelial and subendotelial damage signs in 15-Gy dose groups. T + 15-Gy arm showed more pronounced endothelial cell damage than 15-Gy RT-only arm, 70 days after RT.

Conclusion: T and high-dose RT may lead to vascular damage that seems at least additive.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / toxicity*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / toxicity*
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / pathology
  • Aorta, Thoracic / physiopathology
  • Aorta, Thoracic / radiation effects
  • Endothelial Cells / drug effects
  • Endothelial Cells / pathology
  • Endothelial Cells / radiation effects
  • Female
  • In Vitro Techniques
  • Phenylephrine / pharmacology
  • Rats
  • Rats, Wistar
  • Thorax
  • Trastuzumab
  • Vasoconstriction / drug effects*
  • Vasoconstriction / radiation effects*
  • Vasoconstrictor Agents / pharmacology
  • Vasodilation / drug effects*
  • Vasodilation / radiation effects*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Vasoconstrictor Agents
  • Phenylephrine
  • Trastuzumab