In vitro testing of chemotherapeutic combinations in a rapid thymidine incorporation assay

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Abstract
A total of 199 solid human tumors were tested with a rapid thymidine incorporation assay for sensitivity to one of several clinically used multi-drug combinations and to each agent in the combination separately. Melanomas, lung and breast cancers accounted for the majority of specimens. In 120 specimens, at least one single agent exhibited in vitro activity (80% or greater inhibition of thymidine incorporation), and in 116 of these (96.7%) the drug combination was active in vitro. In the 79 specimens where no single agent was active in vitro, the combination was also inactive in 62 (78.5%). Overall, there was concordance of in vitro activity of the most active single agent and the combination of agents in 89.5% of specimens tested. A lack of significant in vitro synergy was noted in all of the drug combinations and tumor types tested. Of note is the fact that in 141 of the 199 tests (70.9%) either no drug (n = 79) or only 1 drug (n = 62) demonstrated in vitro activity. We conclude that the rapid thymidine incorporation assay can be used to test for in vitro sensitivity to drug combinations, and that sensitivity to a drug combination can be inferred if a tumor is sensitive to any component drug of the combination.