Intravesical chemotherapy: in vitro studies on the relationship between dose and cytotoxicity

The relative importance of two variables, drug concentration and period of exposure, in relation to the therapeutic potential of intravesical chemotherapy was examined in an experimental system. A human bladder cancer cell line was exposed to a range of concentrations of the four drugs commonly used to treat superficial bladder cancer (adriamycin, epodyl, mitomycin-c, thiotepa) for periods of 30, 60 and 120 min. An exponential relationship was observed between clonogenic cell kill and both drug concentration and period of exposure. Thus, under the experimental conditions employed, cytotoxicity is proportional to dose (i.e. concentration X period of exposure). These two variables are of equal importance in relation to tumor cell kill, indicating that maximum therapeutic benefit may be obtained by using the highest concentration achievable for as long as the patient can retain the instillate, bearing in mind the potential increase in toxicity to the patient and the cost.