Pharmacologic effects of paclitaxel in human bladder tumors

Abstract

Purpose: The goal of this study was to determine whether paclitaxel, when given by a 2-h treatment, produces significant cytotoxic effects in human bladder transitional cell carcinoma and hence qualifies as a candidate drug for intravesical treatment.

Methods: Histocultures of surgical specimens from patients (n = 16) were used.

Results: Paclitaxel produced partial inhibition of DNA precursor incorporation in about 70% of tumors and induced apoptosis in about 90% of tumors, while these effects were minimal or not detectable in the remaining tumors. In the responsive tumors, the average maximal inhibition of DNA synthesis was 60% and the average maximal apoptotic index was 15%. Resistance to antiproliferative and apoptotic effects was not always found in the same individual tumors, and no relationship was found between the magnitude of antiproliferative and apoptotic effects in individual tumors. The maximal apoptotic index correlated with the LI for the untreated control (r2 = 0.42, P < 0.01). More than 95% of apoptotic cells were labeled by DNA precursor, whereas not all labeled cells were apoptotic. The pharmacologic effects of paclitaxel in bladder tumors were qualitatively equivalent to those previously found in human head and neck tumors and in human prostate tumors after treatment for longer periods of 24 to 96 h.

Conclusions: These results indicate that a 2-h paclitaxel treatment was sufficient to produce antiproliferation and apoptosis in 70-90% of human bladder tumors, and the apoptotic effect appeared to be linked to proliferation and occurred after DNA synthesis.