Chemosensitivity of human tumor clonogenic cells simultaneously assayed in agar diffusion chambers and in a two-layer...

We have compared plating efficiencies (PE) of 20 fresh and cryopreserved samples of human solid tumors, disaggregated and cloned simultaneously in a two-layer agar culture system (2LACS) and in agar diffusion chambers (ADC). A significant correlation (0.001 less than P less than 0.01, paired t test) was found between PE, confirming that the two methods reflect the same property of tumor cells: their clonogenic potential. The median PE in ADC was 1.4 and 3.3 times higher than that in the 2LACS for cryopreserved and fresh specimens, respectively. One- and two-drug doses, approximately clinically achievable concentrations, were assayed simultaneously in the ADC and in the 2LACS, respectively, on 15 tumor specimens. In this way we evaluated the effects of eight drugs, two to five for each tumor, in a static (2LACS) versus a dynamic (ADC) system. The comparison of percent survival in ADC versus that in the 2LACS at both concentrations tested showed no statistically significant rank correlation. If the data regarding cyclophosphamide and mitomycin, which produced significant cell kill in the ADC and almost none in the 2LACS, were excluded, the rank correlation was still not significant. We conclude that the widely used 2LACS is unsuitable to study cyclophosphamide and mitomycin, for which the ADC technique may be a valid alternative.