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Topotecan Can Compensate for Protracted Radiation Treatment Time Effects in High Grade Glioma Xenografts*

Journal of Neuro-Oncology volume 76, Article number: 31 (2006) Cite this article

Summary

Purpose: Several studies reported that prolongation of overall treatment time of fractionated radiotherapy reduces the chance of tumor control. In the present study, we hypothesize that combining topotecan with irradiation could compensate for this detrimental time effect on the radioresponse. Therefore, we investigated the efficiency of different schedules of topotecan (TPT), radiotherapy (RT) or concomitant combination TPT + RT.

Methods and Materials: Experiments were performed in two human high-grade glioma xenograft models (U87 and GBM Nan1). TPT and RT were delivered at a total dose of 3 mg/kg and 40 Gy, respectively. For the TPT + RT groups, TPT was injected 5 min before radiation. Total radiation doses were delivered in 5, 10, 20, or 30 fractions over 1, 2, 4, or 6 weeks, respectively. The efficiency of TPT, RT, and TPT + RT was evaluated by tumor growth delay (TGD).

Results: At this low total dose, and independent of the schedule, no efficacy was found in TPT-treated glioma xenografts. Conversely, radiotherapy-induced antitumor effect decreased with prolongation of treatment time. For TPT + RT combination, antitumor activity was not influenced by schedule, and tumor response was always comparable to those measured for the shortest and the most efficient irradiation schedule (i.e. 1 week). When treatment was delivered over 4 or 6 weeks in U87 glioma xenografts, therapeutic enhancement ratios reached 2.6 and 3.7, respectively. This indicated that the interaction between ionizing radiation and topotecan was synergistic.

Conclusion: The present study demonstrated that concomitant topotecan can compensate for the detrimental effect of treatment time protraction on radiotherapy efficacy in two malignant glioma xenografts.

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Affiliations

  1. Laboratoire de Recherche en Oncologie, Centre A. Vautrin, Vandœuvre-lès-Nancy, France

    Sophie Pinel & Jean-Louis Merlin

  2. Département d’Oncologie Pédiatrique, CHU, France

    Pascal Chastagner

  3. Département de Radiothérapie, Centre Alexis Vautrin, Vandœuvre-lès-Nancy, France

    Christian Marchal

  4. Department of Radiation Therapy, Massachusetts General Hospital, Boston, MA, 02114, USA

    Alphonse Taghian

  5. Laboratoire de Recherche Centre A. Vautrin, CRAN-UMR7039 CNRS-UHP-INPL, Vandœuvre-lès-Nancy, France

    Muriel Barberi-Heyob

Authors
  1. Sophie Pinel
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  2. Pascal Chastagner
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  3. Jean-Louis Merlin
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  4. Christian Marchal
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  5. Alphonse Taghian
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  6. Muriel Barberi-Heyob
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Corresponding author

Correspondence to Sophie Pinel.

Additional information

This work was supported by the Alexis Vautrin Cancer Center Research Funds and French ‘‘Comité Ré gional de Meurthe-et-Moselle de la Ligue contre le Cancer’’.

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Pinel, S., Chastagner, P., Merlin, JL. et al. Topotecan Can Compensate for Protracted Radiation Treatment Time Effects in High Grade Glioma Xenografts*. J Neurooncol 76, 31 (2006). https://doi.org/10.1007/s11060-005-3666-6

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  • DOI: https://doi.org/10.1007/s11060-005-3666-6

Key words

  • concomitant chemoradiation
  • human malignant glioma xenografts
  • overall treatment time
  • radiotherapy
  • topotecan