Combination of bevacizumab and irradiation on uveal melanoma: an in vitro and in vivo preclinical study

• Published in: Investigational new drugs 2013-02, Vol.31 (1), p.59-65
• Main Authors: Sudaka, Anne, Susini, Antoine, Lo Nigro, Cristiana, Fischel, Jean-Louis, Toussan, Nicolas, Formento, Patricia, Tonissi, Federica, Lattanzio, Laura, Russi, Elvio, Etienne-Grimaldi, Marie-Christine, Merlano, Marco, Milano, Gérard
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiogenesis Inhibitors - administration & dosage; Animals; Antibodies, Monoclonal, Humanized - administration & dosage; Bevacizumab; Biological and medical sciences; Cancer therapies; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Combined Modality Therapy; Drug dosages; Drug therapy; Experiments; Female; General pharmacology; Glaucoma; Growth factors; Human Umbilical Vein Endothelial Cells; Humans; Labeling; Laboratories; Medical research; Medical sciences; Medicine; Medicine & Public Health; Melanoma; Melanoma - drug therapy; Melanoma - pathology; Melanoma - radiotherapy; Metastasis; Mice; Mice, Nude; Monoclonal antibodies; Oncology; Penicillin; Pharmaceutical technology. Pharmaceutical industry; Pharmaceuticals; Pharmacology. Drug treatments; Pharmacology/Toxicology; Preclinical Studies; Radiation therapy; Studies; Tumor Burden - drug effects; Tumors; Uveal Neoplasms - drug therapy; Uveal Neoplasms - pathology; Uveal Neoplasms - radiotherapy; Vascular Endothelial Growth Factor A - metabolism; Xenograft Model Antitumor Assays
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-012-9834-6

Summary Background Radiotherapy (RT) is the standard treatment for uveal melanoma. However it can cause damage to the retina and optic nerve. This study examined the in vitro and in vivo effects of the anti-VEGF monoclonal antibody bevacizumab associated with radiotherapy (RT) on tumor growth and tumor proliferation and vasculature on OCM-1 human uveal melanoma cell line. Methods The anti-proliferative effects of bevacizumab, RT and their combination were tested both in vitro (OCM-1 cells co-cultured with HUVEC cells in Transwell plates) and in vivo (OCM-1 tumor xenografts in nude mice). In addition, treatment effects in vitro on VEGF secretion, as well as treatment effects in vivo on tumor proliferation (Ki67 labelling), tumor vasculature (VEGFR2 labelling) and VEGF tumoral concentration were analyzed. Results Bevacizumab given alone had a significant impact on tumor growth in vivo (and moderate effects in vitro ) . The bevacizumab-RT combination had additive effects in vitro (tumor cell proliferation) and in vivo (tumor growth), which translated into a significant decrease in Ki67 expression, VEGFR2 labelling and VEGF tumoral content. Conclusions The bevacizumab-RT combination could be a promising clinical option to explore for the management of human uveal melanoma, since it may allow RT dose reduction without loss of antitumor efficacy.