Two dimensional view of combination chemotherapy in vitro

A newly developed micromethod to evaluate the cytotoxic effects of drugs on rapidly growing lymphoid cell lines is described, which permits evaluation of more than one variable. This technique allows a checkerboard titration of two drugs to determine the optimum concentration of each needed for the augmentation of the other's cell-killing activity. Such studies have shown that the minimum concentration of vincristine capable of killing a human lymphoid cell population is 5.6 ng/ml. The addition of prednisolone at a concentration of 460 ng/ml reduces the minimum lethal concentration of vincristine to 1.6 ng/ml. When prednisolone is added to vincristine at concentrations of 2.8 mu/ml (a level readily achieved in the serum in vivo) concentrations of vincristine as low as 200 pg/ml are clearly cytotoxic. Similar potentiation of cytotoxicity following the addition of prednisolone has been demonstrated for cytosine arabinoside, but not for daunorubicin and only slightly for methotrexate. The micromethod for the study of optimal doses to be used in drug combinations is simple and gives healthy reproducible results. It should be of considerable utility to anyone interested in screening a wide variety of drug combinations for augmentation or synergistic effects.