EFFICACY OF 5'-NOR-ANHYDROVINBLASTINE (VINORELBINE), AGAINST FRESHLY EXPLANTED CLONOGENIC HUMAN TUMOR-CELLS IN-VITRO

Vinorelbine (5'-nor-anhydrovinblastine) is a semisynthetic vinca alkal oid currently undergoing extensive clinical evaluation. We have studie d the antitumor effect of vinorelbine (final concentrations: 8.4-1000. 0 ng/ml) against freshly explanted clonogenic cells from 102 human tum ors using a capillary soft agar cloning system and have compared the c ompound's activity with vinblastine, vincristine, vindesine, paclitaxe l, docetaxel, and other clinically used anticancer agents. Four specim ens were excluded from further analyses (3 bacterial or fungal contami nation, 1 benign histology). Fifty-one of the remaining 98 (52%) speci mens had adequate colony formation in control capillaries. Vinorelbine showed concentration-dependent antitumor activity against a variety o f solid tumors. At clinically relevant concentrations (0.1 x peak plas ma concentrations in humans) vinorelbine inhibited 21 of 49 specimens (43%) and was as active as vinblastine, vincristine, vindesine, bleomy cin, doxorubicin, 5-fluorouracil, mitomycin-C, cisplatin, methotrexate , and etoposide. However, paclitaxel (71% inhibition, p = 0.006) and d ocetaxel (78% inhibition, p = 0.002) were significantly more active th an vinorelbine. Moreover, vinorelbine showed antitumor activity agains t several tumor types and in particular against breast cancer but also in non-small cell lung cancer. We conclude that vinorelbine has a wid e 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.