Therapeutic efficacy of vinorelbine against pediatric and adult central nervous system tumors |
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Authors: | Matthew L. Hanley Gertrude B. Elion O. Michael Colvin Paul L. Modrich Stephen Keir David J. Adams Darell D. Bigner Henry S. Friedman |
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Affiliation: | (1) Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA, US;(2) Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA Tel. +1-919-684-5301; Fax +1-919-684-6674; E-mail fried003@mc.duke.edu, US;(3) Department of Pharmacology, Duke University Medical Center, Durham, NC 27710, USA, US;(4) Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA, US |
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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. Received: 10 February 1998 / Accepted: 1 April 1998 |
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Keywords: | Vinorelbine Vinca alkaloid CNS tumors Xenografts Mismatch repair |
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