Enhanced antitumor effect of coincident intravesical gemcitabine plus BCG therapy in an orthotopic bladder cancer model.
OBJECTIVE
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.
Department of Urology, Saitama Medical School, Moroyama, Saitama, Japan. m5508985@ra2.so
Minoru
M
Horinaga
Ryuichi
R
Fukuyama
Masahiro
M
Iida
Hitoshi
H
Yanaihara
Yoko
Y
Nakahira
Shoichi
S
Nonaka
Nobuhiro
N
Deguchi
Hirotaka
H
Asakura
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000283:Administration, Intravesical; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D001500:BCG Vaccine / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D005260:Female; D019394:Ki-67 Antigen / Q000032:analysis; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000093542:Gemcitabine
D000276:Adjuvants, Immunologic; D000964:Antimetabolites, Antineoplastic; D001500:BCG Vaccine; D019394:Ki-67 Antigen; D003841:Deoxycytidine; D000093542:Gemcitabine