In vitro effects on DNA synthesis as a predictor of biological effect from chemotherapy

Cell suspensions of tumor or normal bone marrow were incubated in vitro with control media (supplemented Ham's F-10 medium or autologous, pretreatment plasma) and with autologous, posttreatment plasma containing chemotherapeutic agents or their metabolites (treated plasma). Drug-specific perturbation of tumor cell DNA synthesis, as measured by the thymidine labeling index, occurred in treated plasma in 9 of 9 courses where antitumor effect was seen compared to 2 of 8 in which chemotherapy failed. Similar effects on myelocyte labeling index in normal marrow were observed in 14 of 20 courses associated with leukopenia and in 0 of 3 in which there was none. The labeling index was affected in 23 of 29 courses with associated biological effect (79%) versus 2 of 11 courses without biological effect (p = 0.0007). Measurement of changes in labeling index upon exposure to drug-containing plasma may become a useful guide to the choice of antineoplastic chemotherapy.