THIOTEPA PHARMACOKINETICS DURING INTRAVESICAL CHEMOTHERAPY - THE INFLUENCE OF DOSE AND VOLUME OF INSTILLATE ON SYSTEMIC UPTAKE AND DOSE-RATE TO THE TUMOR

ThioTEPA is given intravesically in a variety of schedules to treat su perficial bladder cancer. In this study, the influence of the dose of ThioTEPA and the volume of instillate on the dose rate to the tumour a nd the systemic uptake of ThioTEPA was investigated in eight patients with pTa or pT1 disease. Each patient received four courses of ThioTEP A consisting of 30 mg of drug/30 ml of distilled water, 30 mg/60 ml, 6 0 mg/30 ml and 60 mg/60 ml. Blood and urine samples were obtained for sh following instillation, and ThioTEPA and TEPA levels were measured. The AUC(infinity) values (areas under the concentration-time curve, e xtrapolated to infinity) in plasma were approximately 2 factors higher at the two 60-mg doses. However, the AUC value in the bladder was nea rly 70% higher when 60 mg of drug was instilled in 30 ml of distilled water as compared with 60 mg in 60 ml. Thus, by decreasing the volume of instillate it is possible to increase the dose rate to the tumour w ithout increasing the systemic toxicity.