PHARMACOLOGICAL EFFECTS OF PACLITAXEL IN HUMAN BLADDER-TUMORS

Purpose: The goal of this study was to determine whether paclitaxel, w hen given by a 2-h treatment, produces significant cytotoxic effects i n human bladder transitional cell carcinoma and hence qualifies as a c andidate drug for intravesical treatment. Methods: Histocultures of su rgical specimens from patients (n = 16) were used. Results: Paclitaxel produced partial inhibition of DNA precursor incorporation in about 7 0% of tumors and induced apoptosis in about 90% of tumors, while these effects were minimal or not detectable in the remaining tumors. In th e responsive tumors, the average maximal inhibition of DNA synthesis w as 60% and the average maximal apoptotic index was 15%. Resistance to antiproliferative and apoptotic effects was not always found in the sa me individual tumors, and no relationship was found between the magnit ude of antiproliferative and apoptotic effects in individual tumors. T he maximal apoptotic index correlated with the LI for the untreated co ntrol (r(2) = 0.42, P < 0.01). More than 95% of apoptotic cells were l abeled by DNA precursor, whereas not all labeled cells were apoptotic. The pharmacologic effects of paclitaxel in bladder tumors were qualit atively equivalent to those previously found in human head and neck tu mors and in human prostate tumors after treatment for longer periods o f 24 to 96 h. Conclusions: These results indicate that a 2-h paclitaxe l treatment was sufficient to produce antiproliferation and apoptosis in 70-90% of human bladder tumors, and the apoptotic effect appeared t o be linked to proliferation and occurred after DNA synthesis.