This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Laufer, M. Articles by Egorin, M. J. Search for Related Content PubMed PubMed Citation Articles by Laufer, M. Articles by Egorin, M. J. Social Bookmarking                            What's this?

Intravesical Gemcitabine Therapy for Superficial Transitional Cell Carcinoma of the Bladder: A Phase I and Pharmacokinetic Study

Menachem Laufer, Sakkaraiappan Ramalingam, Mark P. Schoenberg, Mary Ellen Haisfield-Wolf, Eleanor G. Zuhowski, Irene N. Trueheart, Mario A. Eisenberger, Ofer Nativ, Merrill J. Egorin

From Department of Urology and The Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins Hospital, Baltimore, MD; Division of Hematology/Oncology and Department of Pharmacology, University of Pittsburgh School of Medicine, and Program of Molecular Therapeutics/Drug Discovery, University of Pittsburgh Cancer Institute, Pittsburgh, PA; Department of Urology, Sheba Medical Center, Tel Hashomer, and Department of Urology, Bnai Zion Medical Center, Haifa, Israel.

Address reprint requests to Merrill J. Egorin, MD, University of Pittsburgh Cancer Institute, Room G 27-E, Hillman Research Pavilion, 5117 Centre Ave, Pittsburgh, PA 15213-1863; email: egorinmj{at}msx.upmc.edu.

Purpose: To determine maximum-tolerated dose, toxicities, and pharmacokinetics associated with weekly intravesical gemcitabine therapy in patients with superficial bladder cancer.

Patients and Methods: Fifteen patients with recurrent superficial transitional cell bladder carcinoma who experienced prior intravesical therapy failure were studied. Two to 4 weeks after complete transurethral resection, gemcitabine was administered intravesically, once weekly for 6 consecutive weeks. Dwell time was 2 hours. Pharmacokinetics of gemcitabine and its metabolite, 2'2'-difluorodeoxyuridine (dFdU), were studied in plasma and urine. Cystoscopy was repeated 6 weeks after therapy.

Results: Three-patient cohorts were enrolled sequentially at doses of 500, 1,000, and 1,500 mg in 100 mL 0.9% NaCl. Two patients received 2,000 mg in 100 mL. An additional four patients received 2,000 mg in 50 mL. No grade 4 toxicity or clinically relevant myelosuppression was noted. Nine of 13 evaluable patients were recurrence-free at 12 weeks. Low concentrations of gemcitabine ( 1 µg/mL) were present transiently in plasma of all patients receiving 2,000 mg in 50 mL. Gemcitabine was undetectable in plasma of other patients. dFdU was undetectable in plasma of patients receiving less than 1,500 mg. At doses 1,500 mg, dFdU concentrations increased until 90 to 120 minutes and then declined little, if any. Plasma dFdU concentrations implied absorption of 0.5% to 5.5% of instilled dose. Between 61% and 100% of the gemcitabine dose was accounted for in voided urine. No dFdU was measured in voided urine.

Conclusion: Intravesical gemcitabine, at doses up to 2 g/wk, is well tolerated, is associated with minimal systemic absorption, and has promising efficacy in treatment of superficial bladder cancer.

Supported, in part, by a grant from Eli Lilly and Company.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				G. Dalbagni, P. Russo, B. Bochner, L. Ben-Porat, J. Sheinfeld, P. Sogani, M. S. Donat, H. W. Herr, and D. Bajorin Phase II Trial of Intravesical Gemcitabine in Bacille Calmette-Guerin-Refractory Transitional Cell Carcinoma of the Bladder J. Clin. Oncol., June 20, 2006; 24(18): 2729 - 2734. [Abstract] [Full Text] [PDF]

				W. Zoli, L. Ricotti, A. Tesei, P. Ulivi, A. G. Campani, F. Fabbri, R. Gunelli, G. L. Frassineti, and D. Amadori Schedule-Dependent Cytotoxic Interaction between Epidoxorubicin and Gemcitabine in Human Bladder Cancer Cells in Vitro Clin. Cancer Res., February 15, 2004; 10(4): 1500 - 1507. [Abstract] [Full Text] [PDF]