In vitro chemosensitivity of human bladder cancer

The chemosensitivity of fresh specimens of human transitional cell carcinoma was tested using a novel dye exclusion assay based upon Fast Green staining, cytocentrifugation, and H & E counterstaining. Assays were successful (three or more drugs tested) in 22/24 specimens obtained by cytoscopy and 2/2 specimens obtained by open biopsy. Three of 17 specimens had more than 70% cell kill after a 1-hour exposure to thiotepa (500 micrograms/ml), compared with 10/18 after exposure to mitomycin C (250 micrograms/ml), and 19/19 after exposure to doxorubicin (100 micrograms/ml). There was a trend for specimens with high histologic grades or low control viabilities in short-term culture to be more sensitive to mitomycin C than specimens with low histologic grades or high control viabilities. Comparison of these data with published clinical data suggests that intrinsic chemosensitivity may be the most important determinate of clinical response to intravesical chemotherapy with thiotepa, while drug penetration to the tumor cells may primarily determine clinical response to intravesical doxorubicin. Thiotepa may be most valuable in treating large lesions which are intrinsically sensitive, while doxorubicin may be valuable in nearly all small lesions. Improved drug distribution to tumor sites could improve intravesical therapy with doxorubicin.