Antineoplastic drug cytotoxicity in a human bladder cancer cell line: implications for intravesical chemotherapy

The clonogenic survival of MGH-U1 human bladder carcinoma cells treated with melphalan, cisplatin, mitomycin-C, adriamycin, vincristine and 5-fluorouracil was measured to determine the relative contribution of drug concentration and duration of exposure to cytotoxicity and to measure the relative cytotoxic effects of these agents used in intravesical chemotherapy. The survival curves were plotted as a function of log (C X T) and were fitted using a linear least squares analysis. The survival was the same for any given C X T whether this was determined by varying concentration or by varying the duration of exposure in the cases of melphalan, cisplatin, adriamycin, mitomycin-C and 5-fluorouracil. However, duration of exposure was more important than was drug concentration in the case of vincristine cytotoxicity. By utilizing the slope of the log (survival fraction) as a function of log (C X T), the relative cytotoxicity of each agent was determined. Mitomycin C, melphalan, adriamycin and cisplatin had comparable activity in this cell line, whereas vincristine and 5-fluorouracil demonstrated much lower cytotoxicity. We conclude that: mitomycin-C, adriamycin and melphalan were the agents with the greatest cytotoxic efficacy; determination of survival as a function of C X T can be used to separate the relative importance of concentration and of duration of exposure. the cytotoxicity of 5/6 drugs studied was equal when the C X T was kept constant but concentration and exposure times were varied.