In vitro evaluation of synergism or antagonism with combinations of new cytotoxic agents.

New cytotoxics with significant activity both in preclinical and clinical situations continued to be applied in the clinic by empiric means. The use of defined cell lines allows unanticipated antagonism between agents to be identified and to suggest synergistic combinations which need to be tested. By means of a semi-automated MTT assay and median effect analysis, we have identified antagonism in two couplets being evaluated in the clinic: etoposide with paclitaxel and vinorelbine with gemcitabine. Optimal use of these agents in man may require spacing these agents in time to prevent an adverse drug interaction between the agents which may diminish the potential response rate.