Antineoplastic effect of gemcitabine in an animal model of superficial bladder cancer.
OBJECTIVE
To evaluate the safety and efficacy of gemcitabine in an animal model of superficial bladder cancer because of the promising results for treatment of patients with advanced urothelial carcinoma using gemcitabine. The substantial failure rate and toxicity of currently available intravesical agents for treating superficial bladder cancer emphasize the need for alternative drugs.


METHODS
The mouse bladder tumor (MBT-2) model was used in female C3H/eb mice to evaluate gemcitabine toxicity (n = 45) and efficacy (n = 402).


RESULTS
Treatment with varying doses (0.5, 2.5, and 10 mg) of intravesical gemcitabine was well tolerated with no demonstrable side effects. No statistically significant differences in the histologic changes in the bladder wall were observed among the various treatment groups. The efficacy of the drug was tested in two sets of experiments and showed a statistically significant decrease in the bladder weight of the animals treated with gemcitabine compared with those treated with phosphate-buffered saline or untreated controls (61.4 +/- 24.1 mg versus 106.2 +/- 50 mg and 105.5 +/- 46 mg, respectively [P = 0.0001], for an aggressive tumor variant). In the second set of experiments, gemcitabine was given both intraperitoneally and intravesically and resulted in a lower bladder weight (44.5 +/- 15.75 mg and 59.71 +/- 22.5 mg, respectively) compared with the control groups (116.43 +/- 53.91 mg and 122.29 +/- 50 mg, respectively, P = 0.0004).


CONCLUSIONS
The results of the present study indicate that repeated doses of gemcitabine can be safely administered intravesically to C3H/eb mice. This drug displayed significant antineoplastic activity against superficial bladder cancer.
Nativ
Ofer
O
Department of Urology, Bnai Zion Medical Center, Haifa, Israel.
Dalal
Eilata
E
Laufer
Menachem
M
Sabo
Edmond
E
Aronson
Moshe
M
D000283:Administration, Intravesical; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D003556:Cystitis / Q000139:chemically induced; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005355:Fibrosis; D006965:Hyperplasia; D007274:Injections, Intraperitoneal; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009929:Organ Size / Q000187:drug effects; D016037:Single-Blind Method; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D019459:Urothelium / Q000187:drug effects / Q000473:pathology; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine