title: Activity of endovesical gemcitabine in BCG-refractory bladder cancer patients: a translational study.
abstract: Intravesical gemcitabine (Gem) has shown promising activity against transitional cell carcinomas (TCC) of the bladder, with moderate urinary toxicity and low systemic absorption. The present phase II study evaluated the activity of biweekly intravesical treatment with Gem using a scheme directly derived from in vitro preclinical studies. Patients with Bacille Calmette-Guérin (BCG) -refractory Ta G3, T1 G1-3 TCC underwent transurethral bladder resection and then intravesical instillation with 2000 mg Gem diluted in 50 ml saline solution on days 1 and 3 for 6 consecutive weeks. Thirty-eight (95%) of the 40 patients showed persistent negative post-treatment cystoscopy and cytology 6 months after Gem treatment, while the remaining 2 patients relapsed at 5 and 6 months. At a median follow-up of 28 months, recurrences had occurred in 14 patients. Among these, four had downstaged (T) disease, three had a lower grade (G) lesion and three had a reduction in both T and G. Urinary and systemic toxicity was very low, with no alterations in biochemical profiles. In conclusion, biweekly instillation of Gem proved active in BCG-refractory Ta G3, T1 G1-3 TCC. Our results highlight the importance of preclinical studies using in vitro systems that adequately reproduce the conditions of intravesical clinical treatment to define the best therapeutic schedule.
authors.affiliation: Department of Urology, Morgagni-Pierantoni Hospital, Forlì, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Gunelli
authors.forename: E
authors.initials: E
authors.lastname: Bercovich
authors.forename: O
authors.initials: O
authors.lastname: Nanni
authors.forename: M
authors.initials: M
authors.lastname: Ballardini
authors.forename: G L
authors.initials: GL
authors.lastname: Frassineti
authors.forename: N
authors.initials: N
authors.lastname: Giovannini
authors.forename: M
authors.initials: M
authors.lastname: Fiori
authors.forename: E
authors.initials: E
authors.lastname: Pasquini
authors.forename: P
authors.initials: P
authors.lastname: Ulivi
authors.forename: G L
authors.initials: GL
authors.lastname: Pappagallo
authors.forename: R
authors.initials: R
authors.lastname: Silvestrini
authors.forename: W
authors.initials: W
authors.lastname: Zoli
mesh_terms: D000283:Administration, Intravesical; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001500:BCG Vaccine / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D018581:Technology Transfer; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D001500:BCG Vaccine; D003841:Deoxycytidine; D000093542:Gemcitabine