The effect of thio-TEPA on developing and established mammalian bladder tumors

Abstract

The inhibitory effect of thio-TEPA on both developing and established mammalian bladder cancer was tested in the FANFT model system using female C3H/He mice. This model allows the histologic evaluation of the entire target organ, a major advantage over clinical trials, which have relied largely on endoscopic appearance for determination of response. A powerful carcinogen, FANFT is known to cause bladder carcinoma in at least 90% of these animals within 12 months. The tumors develop through a spectrum of morphologic changes including hyperplasia, dysplasia, and carcinoma in situ. Animals were divided into equally sized control and test groups and either thio-TEPA or saline was administered on a schedule designed to correspond to that used in clinical trials. Bladders from 159 mice were evaluated grossly, microscopically and in some instances, ultrastructurally, for the presence of tumor or other intraepithelial lesions. When compared to controls, thio-TEPA had no statistically significant inhibitory effect on either developing or established bladder tumors. The drug did, however, cause a statistically significant decrease in the frequency of high-grade, high-stage lesions when given during tumor development and may retard the evolution of such neoplasms from low-grade noninvasive carcinomas. The correlation of these experimental findings with the reportedly beneficial results of clinical trials is discussed.