Studies on the Intravesical Action of Topically Administered G 3 H-Doxorubicin Hydrochloride in Men: Plasma Uptake and Tumor Penetration (1980)

No AccessJournal of Urology1 Jul 1980Studies on the Intravesical Action of Topically Administered G3H-Doxorubicin Hydrochloride in Men: Plasma Uptake and Tumor Penetration Günther H. Jacobi, and Karl-Heinz Kurth Günther H. JacobiGünther H. Jacobi More articles by this author , and Karl-Heinz KurthKarl-Heinz Kurth Current address: Department of Urology, Erasmus University, Rotterdam, Netherlands. More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(17)55279-9AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail 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. In this regard the penetration of the drug into the bladder wall and the urothelium as a urinary blood barrier is of interest. Using a tritium label we have investigated tumor penetration and transmucosal plasma uptake of doxorubicin hydrochloride after intravesical application in 7 patients with stage A bladder tumors. Of the 7 patients 5 were free of tumor following transurethral resection and 2 had recurrent disease. The patients free of tumor received 40mg. doxorubicin hydrochloride per 30ml. normal saline with 1.2mg. G3H-doxorubicin hydrochloride (27.8mCi./mMol.) intravesically for 2hours. Blood was drawn for up to 120 minutes and plasma was assayed for radioactivity. The patients with recurrent papillary tumor received 2.3mg. labeled doxorubicin hydrochloride along with 40mg. cold substance and underwent transurethral resection 2 hours thereafter. After plasma studies as done in the first group of patients tissue uptake was determined in 3 different specimens: 1) papillary lesion, 2) tumor base and 3) normal urothelium. All patients underwent tests for bone marrow, and renal, hepatic and cardiac side effects. After 54μCi. or 109μCi. 3H-doxorubicin hydrochloride instillation the intravesical radioactivity was 4 X 106 and 7 X 106 disintegrations per minute per milliliter, respectively, but only traces of doxorubicin hydrochloride (20 to 180 disintegrations per minute per milliliter) could be detected in plasma. The highest doxorubicin hydrochloride concentration was measured in the exophytic tumors (1.9 X 104 disintegrations per minute per gram), whereas uptake into tumor base was only one-sixth that amount. Doxorubicin hydrochloridewas almost as high in normal urothelium (1.6 X 104 disintegrations per minute per gram) as in a papillary lesion. No local or systemic side effects were observed. Thus, 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. © 1980 by The American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited ByAli-El-Dein B, El-Baz M, Aly A, Shamaa S and Ashamallah A (2018) Intravesical Epirubicin Versus Doxorubicin for Superficial Bladder Tumors (Stages pTa and pT1): a Randomized Prospective StudyJournal of Urology, VOL. 158, NO. 1, (68-74), Online publication date: 1-Jul-1997.Chai M, Wientjes M, Badalament R, Burgers J and Au J (2018) Pharmacokinetics of Intravesical Doxorubicin in Superficial Bladder Cancer PatientsJournal of Urology, VOL. 152, NO. 2 Part 1, (374-378), Online publication date: 1-Aug-1994.Long J, Prout G, Kai Wong Y and Lin C (2018) The Effect of Verapamil on a Multi-Drug ResistantBladder Carcinoma Cell Line and Its Potential as anIntravesical Chemotherapeutic AgentJournal of Urology, VOL. 143, NO. 5, (1053-1056), Online publication date: 1-May-1990.Jurincic C, Engelmann U, Gasch J and Klippel K (2018) Immunotherapy in Bladder Cancer with Keyhole-Limpet Hemocyanin: A Randomized StudyJournal of Urology, VOL. 139, NO. 4, (723-726), Online publication date: 1-Apr-1988.Crawford E, McKenzie D, Mansson W, Totonchy M, Grossman H, Davis M, Lamm D and Duchek M (2018) Adverse Reactions to the Intravesical Administration of Doxorubicin Hydrochloride: Report of 6 CasesJournal of Urology, VOL. 136, NO. 3, (668-669), Online publication date: 1-Sep-1986.Kurth K, Schröder F, Tunn U, Ay R, Pavone-Macaluso M, Debruyne F, de Pauw M, Dalesio O and ten Kate F (2018) Adjuvant Chemotherapy of Superficial Transitional Cell Bladder Carcinoma:Preliminary Results of a European Organization for Research onTreatment of Cancer Randomized Trial Comparing Doxorubicin Hydrochloride, Ethoglucid and Transurethral Resection AloneJournal of Urology, VOL. 132, NO. 2, (258-262), Online publication date: 1-Aug-1984.Schmidbauer C, Porpaczy P, Georgopoulos A and Rameis H (2018) Absorption of Doxorubicin-Hydrochloride and Mitomycin-C After Instillation into Noninfected and Infected Bladders of DogsJournal of Urology, VOL. 131, NO. 4, (818-821), Online publication date: 1-Apr-1984.Engelmann U, Bürger R, Rumpelt J and Jacobi G (2018) Adriamycin Permeability of the Rat Bladder under Different ConditionsJournal of Urology, VOL. 129, NO. 4, (862-864), Online publication date: 1-Apr-1983.Yu H, Glashan R, Robinson M, Richards B, Fryszman A, Daponte D and Cooper E (2018) Changes in the Urine Protein Profile Following Intravesical DoxorubicinJournal of Urology, VOL. 128, NO. 2, (272-275), Online publication date: 1-Aug-1982.Soloway M (2018) Editorial CommentJournal of Urology, VOL. 128, NO. 2, (275-275), Online publication date: 1-Aug-1982.Jakse G, Hofstädter F and Marberger H (2018) Intracavitary Doxorubicin Hydrochloride Therapy for Carcinoma in Situ of the BladderJournal of Urology, VOL. 125, NO. 2, (185-190), Online publication date: 1-Feb-1981. Volume 124Issue 1July 1980Page: 34-37 Advertisement Copyright & Permissions© 1980 by The American Urological Association Education and Research, Inc.MetricsAuthor Information Günther H. Jacobi More articles by this author Karl-Heinz Kurth Current address: Department of Urology, Erasmus University, Rotterdam, Netherlands. More articles by this author Expand All Advertisement Loading ...