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PHASE I PHARMACOKINETIC STUDY OF A SINGLE INTRAVESICAL INSTILLATION OF GEMCITABINE ADMINISTERED IMMEDIATELY AFTER TRANSURETHRAL RESECTION PLUS MULTIPLE RANDOM BIOPSIES IN PATIENTS WITH SUPERFICIAL BLADDER CANCER

2004; Lippincott Williams & Wilkins; Volume: 172; Issue: 2 Linguagem: Inglês

10.1097/01.ju.0000131770.14409.7f

1527-3792

Juan Palou, Antonio J. Carcas, J. Segarra Tomás, B. Duque, José M. Corberán, Ignacio García-Ribas, Humberto Villavicencio,

Gastric Cancer Management and Outcomes

No AccessJournal of UrologyAdult Urology: Oncology: Renal/Upper Tract/Bladder1 Aug 2004PHASE I PHARMACOKINETIC STUDY OF A SINGLE INTRAVESICAL INSTILLATION OF GEMCITABINE ADMINISTERED IMMEDIATELY AFTER TRANSURETHRAL RESECTION PLUS MULTIPLE RANDOM BIOPSIES IN PATIENTS WITH SUPERFICIAL BLADDER CANCER JUAN PALOU, ANTONIO CARCAS, JOSE SEGARRA, BLANCA DUQUE, JOSE SALVADOR, IGNACIO GARCIA-RIBAS, and HUMBERTO VILLAVICENCIO JUAN PALOUJUAN PALOU More articles by this author , ANTONIO CARCASANTONIO CARCAS More articles by this author , JOSE SEGARRAJOSE SEGARRA More articles by this author , BLANCA DUQUEBLANCA DUQUE More articles by this author , JOSE SALVADORJOSE SALVADOR More articles by this author , IGNACIO GARCIA-RIBASIGNACIO GARCIA-RIBAS More articles by this author , and HUMBERTO VILLAVICENCIOHUMBERTO VILLAVICENCIO More articles by this author View All Author Informationhttps://doi.org/10.1097/01.ju.0000131770.14409.7fAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: In this phase I study we determined the pharmacokinetic and toxicity profiles of a single intravesical instillation of gemcitabine administered immediately after complete transurethral resection (TUR) plus multiple random biopsies. Materials and Methods: Ten patients with superficial bladder cancer clinically staged as Ta/T1 with no carcinoma in situ were included. A single dose of gemcitabine was administered intra-vesically immediately after TUR plus 6 random biopsies. Five patients received 1,500 mg and 5 received 2,000 mg diluted in 100 ml saline. Retention time in the bladder was 60 minutes. Concentrations of gemcitabine and dFdU (2′,2′-difluoro-2′-deoxyuridine) were determined by high pressure liquid chromatography assay. Results: Treatment was clinically well tolerated in all patients. Two patients in the 1,500 mg group had minimal hipogastric discomfort and 1 in the 2,000 mg group had grade 1 bladder spasms. There was no remarkable systemic toxicity on hematology or biochemistry at any dose level on day 12 or 30. One patient per dose level showed tumor recurrence on 3-month repeat cystourethroscopy. Mean maximum gemcitabine concentration was 1.8 μg/ml and the mean last AUC was 158 μg/ml*minute. There was large interpatient variability but no significant differences between the 2 dose levels. Conclusions: Single intravesical instillation of gemcitabine immediately after TUR and multiple random biopsies for superficial bladder cancer are a safe and well tolerated treatment. The favorable toxicity and pharmacokinetic profiles of intravesical gemcitabine support future phase II studies with this agent. References 1 : Primary superficial bladder cancer risk groups according to progression, mortality and recurrence. J Urol2000; 164: 680. Link, Google Scholar 2 : A combined analysis of European Organization for Research and Treatment of Cancer, and Medical Research Council randomized clinical trials for the prophylactic treatment of stage TaT1 bladder cancer. J Urol1996; 156: 1934. Link, Google Scholar 3 : Effectiveness of a single immediate mitomycin C instillation in patients with low risk superficial bladder cancer: short and long-term follow up. J Urol1999; 161: 1120. 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Google Scholar From the Department of Urology Fundació Puigvert, Universidad Autónoma de Barcelona (JP, JS, JS, HV), Barcelona, Department of Clinical Pharmacology, University Hospital La Paz, Universidad Autonoma de Madrid (AC, BD), Madrid and Medical Department, Eli Lilly and Co. (IG-R), Alcobendas, Spain© 2004 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited ByKRAUSE S, FÖRSTER Y, KRAEMER K, FUESSEL S, KOTZSCH M, SCHMIDT U, WIRTH M, MEYE A and SCHWENZER B (2018) VASCULAR ENDOTHELIAL GROWTH FACTOR ANTISENSE PRETREATMENT OF BLADDER CANCER CELLS SIGNIFICANTLY ENHANCES THE CYTOTOXICITY OF MITOMYCIN C, GEMCITABINE AND CISPLATINJournal of Urology, VOL. 174, NO. 1, (328-331), Online publication date: 1-Jul-2005.BROCKS C, BÜTTNER H and BöHLE A (2018) INHIBITION OF TUMOR IMPLANTATION BY INTRAVESICAL GEMCITABINE IN A MURINE MODEL OF SUPERFICIAL BLADDER CANCERJournal of Urology, VOL. 174, NO. 3, (1115-1118), Online publication date: 1-Sep-2005. Volume 172Issue 2August 2004Page: 485-488 Advertisement Copyright & Permissions© 2004 by American Urological Association, Inc.Keywordsbladder neoplasmsadministration, intravesicalbladdergemcitabineMetricsAuthor Information JUAN PALOU More articles by this author ANTONIO CARCAS More articles by this author JOSE SEGARRA More articles by this author BLANCA DUQUE More articles by this author JOSE SALVADOR More articles by this author IGNACIO GARCIA-RIBAS More articles by this author HUMBERTO VILLAVICENCIO More articles by this author Expand All Advertisement PDF DownloadLoading ...