Enhanced Antitumor Effect of Coincident Intravesical Gemcitabine Plus BCG Therapy in an Orthotopic Bladder Cancer Model

• Published in: Urology (Ridgewood, N.J.) Vol. 76; no. 5; pp. 1267.e1 - 1267.e6
• Main Authors: Horinaga, Minoru, Fukuyama, Ryuichi, Iida, Masahiro, Yanaihara, Hitoshi, Nakahira, Yoko, Nonaka, Shoichi, Deguchi, Nobuhiro, Asakura, Hirotaka
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-11-2010
• Subjects: Adjuvants, Immunologic - administration & dosage; Administration, Intravesical; Animals; Antimetabolites, Antineoplastic - administration & dosage; BCG Vaccine - administration & dosage; Cell Line, Tumor; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Dose-Response Relationship, Drug; Female; Ki-67 Antigen - analysis; Mice; Mice, Inbred C3H; Neoplasm Transplantation; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - pathology; Urology
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/j.urology.2010.03.028

Objectives To evaluate the antitumor effect of the coincident administration of intravesical gemcitabine (Gem) plus bacillus Calmette-Guérin (BCG) in an orthotopic bladder cancer model. Methods We evaluated the cytotoxic effect of gemcitabine against MBT-2 cells in vitro. Orthotopic tumors were established by implanting MBT-2 cells into the bladder of syngeneic female C3H mice. Intravesical Gem administration was evaluated at various doses: 0 mg (control); 1, 2, 4, and 8 mg (n = 8 for each group). Next, a comparative evaluation of tumor growth among the control, Gem-alone, BCG-alone, and combined Gem + BCG groups was performed (n = 16 for each group). Therapy was administered at 3-day intervals starting on day 5 and repeated 6 times. To evaluate the proliferative activity among the groups, Ki-67 immunostaining of the tumor was performed. Results Gemcitabine exhibited a dose-dependent antitumor effect. Of the 8 mice in each group treated with a dose of 0, 1, 2, 4, or 8 mg of Gem, 1, 4, 4, 4, 5, and 4 mice failed to develop tumors and survived, respectively. The combination of Gem + BCG (54.1 ± 9.4 days) provided a significant survival advantage compared with BCG-alone (39.0 ± 16.4 days) ( P = .02). Ki-67 expression, representing tumor proliferation, was significantly lower in the combined Gem + BCG group than in the BCG-alone group ( P <.01). Conclusions Our results suggest that intravesical Gem + BCG treatment induces an enhanced antitumor effect against bladder tumors.