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Efficacy of 5′-nor-anhydrovinblastine (vinorelbine), against freshly explanted clonogenic human tumor cells in vitro

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Summary

Vinorelbine (5′-nor-anhydrovinblastine) is a semisynthetic vinca alkaloid currently undergoing extensive clinical evaluation. We have studied the antitumor effect of vinorelbine (final concentrations: 8.4–1000.0 ng/ml) against freshly explanted clonogenic cells from 102 human tumors using a capillary soft agar cloning system and have compared the compound's activity with vinblastine, vincristine, vindesine, paclitaxel, docetaxel, and other clinically used anticancer agents. Four specimens were excluded from further analyses (3 bacterial or fungal contamination, 1 benign histology). Fifty-one of the remaining 98 (52%) specimens had adequate colony formation in control capillaries. Vinorelbine showed concentration-dependent antitumor activity against a variety of solid rumors. At clinically relevant concentrations (0.1 × peak plasma concentrations in humans) vinorelbine inhibited 21 of 49 specimens (43%) and was as active as vinblastine, vincristine, vindesine, bleomycin, doxorubicin, 5-fluorouracil, mitomycin-C, cisplatin, methotrexate, and etoposide. However, paclitaxel (71% inhibition, p = 0.006) and docetaxel (78% inhibition, p = 0.002) were significantly more active than vinorelbine. Moreover, vinorelbine showed antitumor activity against several tumor types and in particular against breast cancer but also in non-small cell lung cancer. We conclude that vinorelbine has a wide spectrum of in vitro activity against freshly explanted human tumors and that the clinical activity of this compound against breast cancer and non-small cell lung cancer is reflected in vitro.

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Authors and Affiliations

  1. Division of Hematology and Oncology, Klinikum rechts der Isar der Technischen Universität München, FRG

    Irene Djuanda, Henrik Depenbrock, Robert Peter, Johannes Rastetter & Axel-R. Hanauske M.D., Ph.D. (Deputy Chief)

  2. Department of Urology, Klinikum rechts der Isar der Technischen Universität München, FRG

    Thomas Block

  3. Department of Surgery, Klinikum rechts der Isar der Technischen Universität München, FRG

    Gabriele Pohlmann

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  1. Irene Djuanda
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  2. Henrik Depenbrock
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  5. Gabriele Pohlmann
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  6. Johannes Rastetter
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  7. Axel-R. Hanauske M.D., Ph.D.
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Djuanda, I., Depenbrock, H., Peter, R. et al. Efficacy of 5′-nor-anhydrovinblastine (vinorelbine), against freshly explanted clonogenic human tumor cells in vitro . Invest New Drugs 14, 153–159 (1996). https://doi.org/10.1007/BF00210786

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