Effect of local hyperthermia of the bladder on mitomycin C pharmacokinetics during intravesical chemotherapy for the treatment of superficial transitional cell carcinoma

Aims To assess the effect of local hyperthermia on the systemic absorption of mitomycin C (MMC) during intravesical chemotherapy for the treatment of superficial transitional cell carcinoma of the bladder, and to establish th e likely safety of this procedure. Methods Group 1 (n = 12) received 20 mg intravesical MMC plus local hyperth ermia, group 2 (n = 13) 20 mg MMC alone, group 3 (n = 16) 40 mg MMC plus lo cal hyperthermia and group 4 (n = 10) 40 mg MMC alone. Patients in groups 1 , 2, and 4 under-went post-tumour resection adjuvant treatment, whereas tho se in group 3 still had tumour present and were treated to eradicate it. In travesical instillation lasted 60 min, with the solution (50 ml) being repl aced after the first 30 min. Blood samples were taken before, and every 15 min during instillation. MMC concentrations in plasma and in urine were det ermined by h.p.l.c. Results The highest MMC plasma concentration (67.9 mg ml(-1)) occurred in a patient in group 3. This value was well below the threshold concentration (400 ng ml(-1)) for myelosuppression. Local hyperthermia associated with th e intravesical chemotherapy enhanced plasma MMC concentrations at 30, 45 an d 60 min compared with chemotherapy alone (Group 1 vs 2, P less than or equ al to0.008). Systemic exposure to MMC was not significantly increased by do ubling the intravesical dose when intravesical chemotherapy alone was admin istered. Patients in group 3 displayed the highest degree of MMC absorption and the greatest variability in pharmacokinetics between patients. Conclusions Local hyperthermia enhances the systemic absorption of MMC duri ng intravesical chemotherapy for bladder cancer. In the doses used, plasma MMC concentrations were always more than six times lower than those shown t o cause toxicity.