DETECTION OF TUMOR-SPECIFIC CYTOTOXIC DRUG ACTIVITY IN-VITRO USING THE FLUOROMETRIC MICROCULTURE CYTOTOXICITY ASSAY AND PRIMARY CULTURES OFTUMOR-CELLS FROM PATIENTS

The semi-automated fluorometric microculture cytotoxicity assay (FMCA) , based on the measurement of fluorescence generated from cellular hyd rolysis of fluorescein diacetate (FDA) by viable cells, was employed f or cytotoxic drug sensitivity testing of tumor cells from patients wit h hematological or solid tumors. In total, 390 samples from 20 diagnos es were tested with up to 12 standard cytotoxic drugs. The technical s uccess rate for different tumor types ranged from 67 to 95%. Fluoresce nce was linearly related to cell number but variably steep depending o n tumor type. Samples from most solid tumors thus showed higher signal -to-noise ratios than hematological samples. A wide spectrum of in vit ro drug activity was obtained, with acute leukemias and non-Hodgkin's lymphomas being sensitive to almost all tested drugs, whereas renal an d adrenocortical carcinomas were essentially totally resistant. Betwee n these extremes were samples of breast and ovarian carcinomas and sar comas. When in vitro response was compared with known clinical respons e patterns, a good correspondence was observed. The results indicate t hat the FMCA is a rapid and efficient method for in vitro measurement of tumor-specific drug activity both in hematological and in solid tum ors. The assay may be suitable for new drug development and direction of phase-2 trials to suitable patients. (C) 1994 Wiley-Liss, Inc.