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Preclinical impact of bevacizumab on brain and tumor distribution of irinotecan and temozolomide

Journal of Neuro-Oncology volume 122, pages 273–281 (2015)Cite this article

Abstract

Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Prognosis of GBM patients is poor with median overall survival around 15 months. Temozolomide is the chemotherapeutic agent used in the standard of care of newly diagnosed GBM patients relying on radiotherapy with concurrent chemotherapy followed by chemotherapy alone. Irinotecan has shown some efficacy in recurrent malignant gliomas. Bevacizumab has been combined with irinotecan in the treatment of recurrent GBM and with temozolomide in newly diagnosed GBM. As the efficacy of GBM treatments relies on their brain distribution through the blood brain barrier, the aim of the present preclinical work was to study, in in vivo models, the impact of bevacizumab on brain and tumor distribution of temozolomide and irinotecan. Our results show that bevacizumab pre-treatment was associated with a reduced temozolomide brain distribution in tumor-free mice. In tumor bearing mice, bevacizumab increased temozolomide tumor distribution, although not statistically significant. In both tumor-free and tumor-bearing mice, bevacizumab does not modify brain distribution of irinotecan and its metabolite SN-38. Bevacizumab impacts brain distribution of some anti-tumor drugs and potentially their efficacy in GBM. Further studies are warranted to investigate other therapeutic combination.

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Fig. 1
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Abbreviations

CPT-11:

Irinotecan

SN-38:

7-Ethyl-10-hydroxycamptothecin

TMZ:

Temozolomide

AUC:

Area under the curve

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Acknowledgments

The authors thank Stella Ghouti for grammatical English corrections and Georges Khazen for statistical expertise.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Clinical Pharmacy Department - EA 4123, College of Pharmacy, Paris Sud University, 5 rue Jean Baptiste Clement, 92296, Châtenay Malabry, France

    Lauriane Goldwirt, Robert Farinotti & Christine Fernandez

  2. Department of Neurosurgery, Pitie-Salpetriere Hospital, AP-HP, 75013, Paris, France

    Kevin Beccaria & Alexandre Carpentier

  3. Pharmacy Department, Saint Antoine Hospital, AP-HP, 75012, Paris, France

    Christine Fernandez

  4. Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, UM 75, U 1127, UMR 7225, ICM, 75013, Paris, France

    Ahmed Idbaih, Charlotte Schmitt, Camille Levasseur & Marianne Labussiere

  5. Department of Neurooncology, Pitie-Salpetriere Hospital, AP-HP, 75013, Paris, France

    Ahmed Idbaih

  6. Department of Pharmaceutical Sciences, School of Pharmacy, Lebanese American University, Byblos, Lebanon

    Aline Milane

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  1. Lauriane Goldwirt
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Correspondence to Lauriane Goldwirt.

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Goldwirt, L., Beccaria, K., Carpentier, A. et al. Preclinical impact of bevacizumab on brain and tumor distribution of irinotecan and temozolomide. J Neurooncol 122, 273–281 (2015). https://doi.org/10.1007/s11060-015-1717-1

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Keywords

  • Irinotecan
  • SN-38
  • Temozolomide
  • Tumor distribution
  • Brain distribution
  • Glioblastoma