IN-VITRO CYTOTOXIC ACTIVITY OF TAXOL(R) AND TAXOTERE ON PRIMARY CULTURES AND ESTABLISHED CELL-LINES OF HUMAN OVARIAN-CANCER

The activity of Taxol(R) and Taxotere was evaluated on three established cell lines and 19 primary cultures of human ovarian cancers and compared with that of cisplatin and doxorubicin. The cytotoxic activity of the different drugs was assessed with a clonogenic assay in cell lines and with a proliferative assay (based on [H-3]thymidine [H-3-dT] incorporation of cells grown in double-layer agarose for four days) in primary tumor cultures. The two assays run in parallel on the OVCA432 cell line provided similar ranking of activity for all the drugs. Taxotere was more cytotoxic than Taxol(R) in two cell lines and showed the same degree of activity in one cell line. Moreover, the two drugs were more cytotoxic than cisplatin and doxorubicin in all cell lines. In primary cultures both Taxol(R) and Taxotere were less active than cisplatin and doxorubicin. An activity by at least one of these two compounds was seen in 9 of 19 cases. Taxol(R) was more frequently active than Taxotere and generally more potent. A direct relationship was observed between the proliferative activity of the tumor cell population and response to Taxol(R) and/or Taxotere. In fact, cell lines that were highly sensitive to Taxol(R) and Taxotere displayed H-3-dT labeling index (LI) values much higher than those observed in primary cultures (39% to 45% versus 0.2% to 12.6%). Again, primary cultures sensitive to Taxol(R) and/or Taxotere were characterized by a median H-3-dT LI value about three times higher than that observed in resistant cultures (8.0% versus 2.6%).