Mervyn Israel

Intravesical doxorubicin for prophylaxis in the management of recurrent superficial bladder carcinoma.

Intermittent intravesical doxorubicin chemotherapy was given to 27 patients with multiple recurrent superficial transitional cell carcinoma of the bladder, including 12 who had become refractory to intravesical thiotepa. The starting dose was 60 mg. doxorubicin diluted in 40 to 50 ml. normal saline solution and doses were increased to 90 mg. The duration of instillation was 60 minutes. Treatments were administered every 3 weeks for a total of 8 doses, then every 6 weeks for 2 doses and then every 12 weeks for 2 doses. Therapy then ended for patients who were rendered free of disease. Cystoscopy and urinary cytology studies were performed every 3 months throughout the study. Of the patients 30 per cent had intermittent episodes of dysuria, 26 per cent had urinary frequency, 41 per cent had hematuria and 15 per cent had bladder spasms. None of these toxicities required discontinuation of the drug. Analysis of plasma samples for doxorubicin and metabolites revealed no systemic absorption and there was no myelosuppression. Of the 27 patients 15 (56 per cent) have maintained complete eradication of bladder cancer without any evidence of residual carcinoma detected endoscopically or with urinary cytology. Recurrent disease developed in 9 patients (33 per cent) while on therapy, including 3 with muscle invasion. Cystoscopy has remained grossly negative in 3 patients who have had positive class 5 cytology studies. The median duration of followup in all patients has been 12 months, with a range of 6 to 24 months. We conclude that intravesical doxorubicin is tolerated well and is effective in the management of multiple recurrent superficial transitional cell carcinoma of the bladder.

Distribution of radioactivity and anthracycline-fluorescence in tissues of mice one hour after [14C]-labeled AD 32 administration

SummaryLevels of radioactivity and total anthracycline fluorescence in tissues of A/JAX mice were compared 1 h after IV administration of unlabeled or [14C]-labeled AD 32 (50 mg/kg). Highest levels of both fluorescence and radioactivity were found in the small intestine (including contents) and liver, a result consistent with the known hepatobiliary excretion of AD 32 and metabolites. Significant accumulations of radioactivity and fluorescence were found in kidney, spleen, large intestine (including contents), lung, and heart. Lesser levels were found in muscle and fat. Little radioactivity and fluorescence were found in brain. Liquid chromatographic analysis of extracts of small intestine and liver homogenates showed N-trifluoroacetyladriamycin (AD 41) as the major fluorescent species, and also revealed N-trifluoroacetyladriamycinol (AD 92) and occasional low levels of AD 32. In addition, there was a major peak of nonfluorescent radioactive material and two fluorescent nonradioactive signals (unknowns 1 and 2), indicative of cleavage of the radiolabel from the chromophore.