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Antitumor activity and pharmacokinetics of oral gimatecan on pediatric cancer xenografts

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Abstract

Purpose

This study compared the antitumor activity and the pharmacological profile of gimatecan given orally and irinotecan (CPT-11) on pediatric tumor xenografts.

Experimental design

Gimatecan was tested in two neuroblastoma cell lines (SK-N-DZ and SK-N-(BE)2c) and on TE-671 rhabdomyosarcoma cells using two different schedules. We characterized its pharmacokinetic profile in nude mice bearing human SK-N-DZ and TE-671 cell lines.

Results

Gimatecan appears to have high plasma disposition. The drug was present in plasma almost completely as the intact lactone form and showed substantial activity in all tumor models. Prolonged daily treatment with low doses of gimatecan produced significant tumor regression in all tumor xenografts.

Conclusion

The antitumor activity and the promising pharmacological profile indicate gimatecan as an excellent candidate for clinical treatment of pediatric tumors.

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Authors and Affiliations

  1. Department of Oncology, Istituto di Ricerche Farmacologiche “Mario Negri”, Via La Masa 19, 20156, Milan, Italy

    Massimo Zucchetti, Maurizio D’Incalci & Daniele Forestieri

  2. Division of Pediatric Oncology, Catholic University of Rome, Largo A. Gemelli 8, 00168, Rome, Italy

    Daniela Meco, Angela Maria Di Francesco, Tiziana Servidei, Valentina Patriarca, Gabriella Cusano & Riccardo Riccardi

  3. Research & Development, Sigma-Tau, Rome, Italy

    Claudio Pisano

Authors
  1. Massimo Zucchetti
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  2. Daniela Meco
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  3. Angela Maria Di Francesco
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  4. Tiziana Servidei
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  5. Valentina Patriarca
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  6. Gabriella Cusano
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  7. Maurizio D’Incalci
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  8. Daniele Forestieri
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  9. Claudio Pisano
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  10. Riccardo Riccardi
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Corresponding author

Correspondence to Massimo Zucchetti.

Additional information

The authors Massimo Zucchetti and Daniela Meco contributed equally to the work.

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Zucchetti, M., Meco, D., Di Francesco, A.M. et al. Antitumor activity and pharmacokinetics of oral gimatecan on pediatric cancer xenografts. Cancer Chemother Pharmacol 66, 635–641 (2010). https://doi.org/10.1007/s00280-009-1201-8

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  • DOI: https://doi.org/10.1007/s00280-009-1201-8

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