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Cancer Chemotherapy and Pharmacology

, Volume 42, Issue 6, pp 479–482 | Cite as

Therapeutic efficacy of vinorelbine against pediatric and adult central nervous system tumors

  • Matthew L. Hanley
  • Gertrude B. Elion
  • O. Michael Colvin
  • Paul L. Modrich
  • Stephen Keir
  • David J. Adams
  • Darell D. Bigner
  • Henry S. Friedman
ORIGINAL ARTICLE

Abstract

Purpose: The activity of vinorellbine, a new semisynthetic vinca alkaloid, was evaluated against a battery of human tumor xenografts derived from adult and pediatric CNS malignancies. Methods: Tumors included adult high-grade gliomas (D-54 MG, D-245 MG), childhood high-grade gliomas (D-212 MG, D-456 MG), medulloblastomas (D-341 MED, D-487 MED), ependymomas (D-612 EP, D-528 EP), and a mismatch repair-deficient procarbazine-resistant glioma [D-245 MG (PR)]. Tumors were grown subcutaneously in athymic nude mice and vinorelbine was administered at a dose of 11 mg/kg on days 1, 5, and 9. Additionally, vinorelbine was also administered in combination with BCNU against D-54 MG. Results: Vinorelbine produced statistically significant growth delays in D-456 MG, D-245 MG, and D-245 MG (PR). No statistically significant growth delays were observed in D-54 MG, D-487 MED, D-212 MG, D-528 EP, D-341 MED or D-612 EP. The antitumor effects of the vinorelbine/BCNU combination were additive. Growth delays observed in the procarbazine-resistant line [D-245 MG (PR)] were greater than twofold the delays seen in the parent line (D-245 MG). Vincristine was equally potent against D-245 MG and D-245 MG (PR). Taxol demonstrated little activity against D-245 MG but produced 32- and 18-day growth delays in D245 MG (PR). Conclusions: These studies indicate that vinorelbine possesses antitumor activity against several glioma tumor xenografts with marked activity in a mismatch repair deficient-tumor.

Key words Vinorelbine Vinca alkaloid CNS tumors Xenografts Mismatch repair 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Matthew L. Hanley
    • 1
  • Gertrude B. Elion
    • 1
  • O. Michael Colvin
    • 1
  • Paul L. Modrich
    • 1
  • Stephen Keir
    • 1
  • David J. Adams
    • 1
  • Darell D. Bigner
    • 1
  • Henry S. Friedman
    • 1
  1. 1.Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USAUS

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