Normal tissues toxicities triggered by combined anti-angiogenic and radiation therapies: hurdles might be ahead.

Details

Serval ID
serval:BIB_8B67C47989F7
Type
Article: article from journal or magazin.
Collection
Publications
Title
Normal tissues toxicities triggered by combined anti-angiogenic and radiation therapies: hurdles might be ahead.
Journal
British journal of cancer
Author(s)
Mangoni M., Vozenin M.C., Biti G., Deutsch E.
ISSN
1532-1827 (Electronic)
ISSN-L
0007-0920
Publication state
Published
Issued date
10/07/2012
Peer-reviewed
Oui
Volume
107
Number
2
Pages
308-314
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Combined-modality therapy is a promising approach to improve the therapeutic index of radiotherapy. However, these improvements could come at the cost of increased toxicities. Clinical trials evaluating anti-tumour efficacy of bevacizumab combined with radiotherapy have encountered unexpected side effects. This study is the first systematic evaluation of normal tissue toxicity triggered by anti-angiogenic agents combined with radiation therapy in mice.
Effect of a mouse anti-VEGF antibody was monitored on acute toxicity studying radiation-induced intestinal ulceration (12 Gy TBI); on subacute toxicity using a model of oral mucositis (16.5 Gy); on late radiation injuries by monitoring lung fibrosis (bleomycin and 19 Gy).
Combination of irradiation with anti-VEGF antibody enhanced intestinal damages with severe epithelial ulcerations, had no adverse impact on oral mucositis and dramatically worsened the fibrotic picture induced by bleomycin and irradiation to the lung.
These reports bring to light the important questions about safety and underscore the need for appropriate preclinical modelling of the impact on normal tissues of novel drug-radiation regimens. Our findings also highlight the complexity of anti-VEGF action, which could in defined conditions exert tissue-specific protection. The findings indicate that the combination of targeted drugs with radiotherapy should be approached with caution.

Keywords
Angiogenesis Inhibitors/toxicity, Animals, Bleomycin/toxicity, Combined Modality Therapy/adverse effects, Combined Modality Therapy/methods, Female, Fibrosis/etiology, Intestines/radiation effects, Lung/pathology, Lung/radiation effects, Mice, Mice, Inbred C57BL, Mouth Mucosa/pathology, Mouth Mucosa/radiation effects, Radiation Injuries, Experimental/etiology, Radiotherapy/adverse effects, Radiotherapy Dosage, Stomatitis/etiology
Pubmed
Web of science
Open Access
Yes
Create date
30/04/2018 15:22
Last modification date
20/08/2019 14:50
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