INVITRO TESTING OF CHEMOTHERAPEUTIC DRUG-COMBINATIONS IN ACUTE MYELOCYTIC-LEUKEMIA USING THE FLUOROMETRIC MICROCULTURE CYTOTOXICITY ASSAY (FMCA)

The fluorometric microculture cytotoxicity assay (FMCA) was employed f or analysing the effect of different chemotherapeutic drug combination s and their single constituents in 44 cases of acute myelocytic leukae mia (AML). A large heterogeneity with respect to cell kill was observe d for all combinations tested, the interactions ranging from antagonis tic to synergistic in terms of the multiplicative concept for drug int eractions. However, an 'additive' model provided a significantly bette r fit of the data compared to the effect of the most active single age nt of the combination (Dmax) for several common antileukaemic drug com binations. When the two interaction models were related to treatment o utcome 38% of the non-responders showed preference for the additive mo del whereas the corresponding figure for responders was 80%. Overall, in 248 of 290 (85%) tests performed with drug combinations, there was an agreement between the effect of the combination and that of the mos t active single component. Direct comparison of Dmax and the combinati on for correlation with clinical outcome demonstrated only minor diffe rences in the ability to predict drug resistance. The results show tha t FMCA appear to report drug interactions in samples from patients wit h AML in accordance with clinical experience. Furthermore, testing sin gle agents as a substitute for drug combinations may be adequate for d etection of clinical drug resistance to combination therapy in AML.