Studies on the Intravesical Action of Topically Administered G 3 H-Doxorubicin Hydrochloride in Men: Plasma Uptake and Tumor Penetration

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Abstract
Doxorubicin hydrochloride has been used for the treatment and prevention of recurrences of transitional cell carcinoma. Ideal indications for the drug and side effects have not been determined. The penetration of the drug into the bladder wall and the urothelium as a urinary blood barrier is of interest. Using a tritium label, tumor penetration and transmucosal plasma uptake of doxorubicin hydrochloride were investigated after intravesical application in 7 patients with stage A bladder tumors. Of the 7 patients 5 were tumor-free following transurethral resection and 2 had recurrent disease. The patients free of tumor received 40 mg doxorubicin hydrochloride per 30 ml normal saline with 1.2 mg 3H-doxorubicin hydrochloride (27.8 mCi/mmol) intravesically for 2 h. Blood was drawn for up to 120 min and plasma was assayed for radioactivity. The patients with recurrent papillary tumor received 2.3 mg labeled doxorubicin hydrochloride with 40 mg cold substance and underwent transurethral resection 2 h thereafter. After plasma studies as done in the 1st group of patients, tissue uptake was determined in the following 3 different specimens: papillary lesion, tumor base and normal urothelium. All patients underwent tests for bone marrow, and renal, hepatic and cardiac side effects. After 54 .mu.Ci or 109 .mu.Ci 3H-doxorubicin hydrochloride instillation, the intravesical radioactivity was 4 .times. 106 and 7 .times. 106 dpm/ml, respectively, but only traces of doxorubicin hydrochloride (20-180 dpm/ml) could be detected in plasma. The highest doxorubicin hydrochloride concentration was measured in the exophytic tumors (1.9 .times. 104 dpm/g); uptake into tumor base was only 1/6 that amount. Doxorubicin hydrochloride was almost as high in normal urothelium (1.6 .times. 104 dpm/g) as in a papillary lesion. No local or systemic side effects were observed. Doxorubicin hydrochloride seems to be beneficial for patients with carcinoma in situ and superficial papillary tumors but less helpful for patients with infiltrating carcinoma. The lack of systemic effects is explained by the negligible plasma uptake after intravesical instillation.