Effects of Intravesical Instillation of 5-Fluorouracil and Interferon in Patients with Recurrent Superficial Urinary Bladder Carcinoma: A Clinical and Pharmacodynamic Study

Abstract

Eleven patients with recurrent superficial bladder tumours were treated with 6 weekly instillations of 10 million IU Introna and 1000 mg 5-fluorouracil for 1 h. Before and immediately after the first treatment biopsies were taken from normal urothelium and tumour for analysis of thymidylate synthase (TS). One papillary tumour was left as a marker. Tumour tissue had 9 times higher TS concentrations than normal urothelium (0.97 versus 0.11 pmol/g, p < 0.005). Despite a large variation in TS concentration in the tumours between different patients (range 0.02-2.24 pmol/g), after instillation the TS concentration decreased significantly in all but one patient. Six patients had complete and 2 had partial tumour regression after treatment. The effect was inversely correlated to the initial TS value. A low TS value seemed to predict a good response. The data suggest that weekly administrations are not sufficient in those with high TS concentrations. New treatment schedules may be beneficial in those with highly proliferating bladder tumours.

Substitution of anti-androgens and tegafur-uracil combination therapy for castration-resistant prostate cancer: Results of a multi-center randomized phase II study

“…Invasive bladder cancer has higher TS expression, and it has a positive correlation with that of proliferation markers. Furthermore, patients with a high level of TS immunostaining had a significantly poorer prognosis in bladder cancer (13,14). However, in prostate cancer, the expression level of these enzymes has not fully been examined, and the correlation of their expression level with stage, Gleason score or prognosis has not been investigated.…”