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Effects of the VEGFR inhibitor ZD6474 in combination with radiotherapy and temozolomide in an orthotopic glioma model

  • Lab. Investigation-Human/Animal Tissue
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Abstract

Aim of the study The extensive neovascularisation of malignant glioma is mainly influenced by vascular endothelial growth factor (VEGF). The effect of ZD6474, a potent inhibitor of VEGF-receptor-2, was evaluated in combination with either radiotherapy or temozolomide. Methods The effects on glioma growth were investigated in the intracerebral BT4C rat glioma model. ZD6474 30 mg/kg was given alone or in combination with radiotherapy 12 Gy × 1 or with temozolomide 100 mg/kg for 3 days. Two different experiments were performed comparing ZD6474 to radiotherapy or temozolomide. For each experiment 28 animals were randomized into four groups. Results ZD6474 in combination with radiotherapy significantly decreased tumour area by 66% compared with controls whereas the combination with temozolomide decreased tumour area by 74%. Conclusions ZD6474 in combination with two standard modalities in the treatment of malignant glioma, radiotherapy and chemotherapy, markedly decreased the growth of an intracerebral experimental glioma. These results justify further investigations of these therapies in combination.

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Acknowledgements

Kerstin Bergh is acknowledged for skilful technical assistance and Britt-Inger Gladzki for taking great care of the animals. This work was supported by grants from the Swedish Society Against Cancer, Lion’s Cancer Research Foundation, and J. C. Kempes Minnes Stipendiefond, Umeå University, Sweden. The work was also supported by an unrestricted research grant from Schering-Plough Sweden AB. ZD6474 was provided from AstraZeneca, Alderley Park, UK.

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Authors and Affiliations

  1. Department of Radiation Sciences, Oncology, Umeå University, 901 85, Umeå, Sweden

    Maria Sandström, Mikael Johansson, Per Bergström & Roger Henriksson

  2. Department of Pharmacology and Clinical Neuroscience, Neurosurgery, Umeå University, 901 85, Umeå, Sweden

    A. Tommy Bergenheim

  3. AstraZeneca, Sodertalje, Sweden

    Roger Henriksson

Authors
  1. Maria Sandström
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  2. Mikael Johansson
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  3. Per Bergström
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  4. A. Tommy Bergenheim
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  5. Roger Henriksson
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Corresponding author

Correspondence to Maria Sandström.

Additional information

Preliminary parts of this study were presented on EANO, Edinburgh, May 2005 and on ECCO, Paris, October 2005.

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Sandström, M., Johansson, M., Bergström, P. et al. Effects of the VEGFR inhibitor ZD6474 in combination with radiotherapy and temozolomide in an orthotopic glioma model. J Neurooncol 88, 1–9 (2008). https://doi.org/10.1007/s11060-008-9527-3

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  • DOI: https://doi.org/10.1007/s11060-008-9527-3

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