PRECLINICAL ACTIVITY OF TAXOTERE (RP-56976, NSC-628503) AGAINST FRESHLY EXPLANTED CLONOGENIC HUMAN TUMOR-CELLS - COMPARISON WITH TAXOL AND CONVENTIONAL ANTINEOPLASTIC AGENTS

Taxotere (TER) and taxol (TA) are new antitumour agents currently unde rgoing clinical evaluation. We studied the antineoplastic effects of t hese agents (final concentrations: 4.0, 0.4, 0.04 mu mol/l) on the in vitro proliferation of clonogenic cells from freshly explanted human t umours using a capillary soft agar cloning system. We also compared th e activity of these new compounds to conventional antineoplastic agent s (bleomycin, cisplatin, dacarbazine, doxorubicin, etoposide, 5-fluoro uracil, vinblastine, interferon-alpha(2)). Using a 21-28-day continuou s drug exposure, 54/81 specimens (67%) were evaluable for comparisons, and using a 1-h drug exposure followed by 21-28 days incubation, 50/8 0 specimens (63%) were. similarly evaluable. With both schedules, TA a nd TER showed concentration-related antitumour activity. At 0.4 mu mol /l, median colony survival was 0.61 x control (range 0.09-0.96) for TA and 0.51 x control (0.15-0.81) for TER in the 1-h incubation (P=0.000 2). Median colony formation was also reduced significantly more by TER as compared to TA in the long-term incubation schedule. Statistical a nalysis indicated that TER but not TA was significantly more active th an cisplatin (P=0.02), doxorubicin (P=0.01), 5-fluorouracil (P=0.01) a nd interferon-alpha(2) (P=0.01). We conclude that TER and TA are more active against in vitro tumour colony formation from freshly explanted human tumours. TER appears to be slightly more active than taxol and promises to be active against tumours resistant to conventional antine oplastics.