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A Methodological Approach to the Prediction of Anticancer Drug Effect in Humans¹

Departments of Medicine [W. J. D.], Microbiology [V. K. G., D. W. D., R. N. H.], and Surgery [C. M. B.] and Comprehensive Cancer Center [W. J. D., V. K. G., C. M. B., R. N. H.], University of Alabama in Birmingham, Birmingham, Alabama 35294

Tumor cells from animals and humans were treated with drugs under tissue culture conditions. Tumor cells from the sensitive L1210 model were studied first. A dose-response curve was derived between drug exposure and subsequent cytotoxicity in L1210. The concentration of drug and duration of exposure were factors critical to the subsequent development of in vitro cytotoxicity. The in vitro dosage which effected 50% leukemic cell death in L1210 cells correlated with reported in vivo drug levels. Other tumor models and human neoplastic cells were studied at this dosage level. A good correlation was noted in these studies between the in vivo responsiveness and the in vitro chemotherapy results in both animals and humans. It was suggested by these results that it may be possible to predict cancericidal drug activity for individual neoplasms by assaying the tumor cells in vitro for drug sensitivity.

¹ This research was supported by Research Grant R01-CA-14125 from the National Cancer Institute, NIH.

² To whom requests for reprints should be addressed, at Lyons-Harrison Research Building, Room 642, Division of Hematology and Oncology, University of Alabama in Birmingham, The Medical Center, Birmingham, Ala. 35294.

Received 7/24/78. Accepted 10/30/78.