EFFECTS OF INTRAVESICAL INSTILLATION OF 5-FLUOROURACIL AND INTERFERONIN PATIENTS WITH RECURRENT SUPERFICIAL URINARY-BLADDER CARCINOMA - A CLINICAL AND PHARMACODYNAMIC STUDY

Eleven patients with recurrent superficial bladder tumours were treate d with 6 weekly instillations of 10 million IU Introna (R) and 1000 mg 5-fluorouracil for 1 h. Before and immediately after the first treatm ent biopsies were taken from normal urothelium and tumour for analysis of thymidylate synthase (TS). One papillary tumour was left as a mark er. Tumour tissue had 9 times higher TS concentrations than normal uro thelium (0.97 versus 0.11 pmol/g, p < 0.005). Despite a large variatio n 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 inversel y 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 schedu les may be beneficial in those with highly proliferating bladder tumou rs.