Journal of Neuro-Oncology

, Volume 85, Issue 2, pp 181–189 | Cite as

Enhancement of cisplatin efficacy by thalidomide in a 9L rat gliosarcoma model

  • Susan Murphy
  • Ross A. Davey
  • Xiao-Qing Gu
  • Miriam C. Haywood
  • Lauren A. McCann
  • Laurence E. Mather
  • Frances M. Boyle
Lab. Investigation-human/animal tissue


With the aim of improving the treatment of glioblastoma multiforme, we investigated the potential of thalidomide to enhance the effectiveness of cisplatin chemotherapy in a rat glioma model. Female F344 rats were implanted with 9L gliosarcoma tumors either intracranially or subcutaneously and treated with 1 mg/kg cisplatin injected i.p. or with 1% thalidomide in the food or with these treatments combined. Cisplatin in combination with thalidomide significantly reduced both the subcutaneous tumor volume at 30 days to 22 ± 5% (mean ± SEM, P < 0.001) and the intracranial tumor volume at 18 days to 44 ± 15% (P < 0.05) of that with cisplatin alone. Thalidomide selectively increased the cisplatin concentration 10–fold in intracranial tumors (P < 0.05) and 2-fold in the subcutaneous tumors (P < 0.05) without increasing its concentration in major organs including brain and kidney. Cisplatin combined with thalidomide caused a significant decrease in vascular endothelial growth factor (VEGF) levels by 73% in intracranial tumors (P < 0.05) and by 50% in subcutaneous tumors (< 0.05) and caused the level of active hepatic growth factor (a-HGF) to double in both the subcutaneous and intracranial tumors (< 0.05), suggesting this treatment altered the vasculature in these tumors. We conclude the increased efficacy of cisplatin in the presence of thalidomide was due to the selective increase in cisplatin concentration within the tumors and speculate that this is the result of thalidomide or the cisplatin/thalidomide combination, selectively altering the tumor vasculature. Based on the selective effects of thalidomide on tumor cisplatin concentrations and the resulting increase in efficacy, thalidomide may also increase the efficacy of other drugs that are presently considered ineffective against glioma.


9L gliosarcoma Cisplatin Glioma Hepatic growth factor Thalidomide Vascular endothelial growth factor 



This work was supported by the Andrew Olle Foundation, Department of Medical Oncology, and the Bill Walsh Cancer Research Trust, Royal North Shore Hospital, Sydney, Australia.


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Susan Murphy
    • 1
  • Ross A. Davey
    • 1
  • Xiao-Qing Gu
    • 2
  • Miriam C. Haywood
    • 1
  • Lauren A. McCann
    • 1
  • Laurence E. Mather
    • 2
  • Frances M. Boyle
    • 3
  1. 1.Bill Walsh Cancer Research Laboratories, Royal North Shore HospitalUniversity of SydneySt LeonardsAustralia
  2. 2.Department of Anaesthesia and Pain Management, Royal North Shore HospitalUniversity of SydneySt LeonardsAustralia
  3. 3.Medical Oncology Department, Royal North Shore HospitalUniversity of SydneySt LeonardsAustralia

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