Results of a European comparative randomized study comparing oral bropirimine versus intravesical BCG treatment in BCG-naive patients with carcinoma in situ of the urinary bladder. European Bropirimine Study Group.
OBJECTIVE
This European phase III clinical trial was part of an intercontinental study which was closed prematurely by the sponsor. The study was designed to compare the effects of oral bropirimine with intravesical BCG, the current standard treatment in patients with newly diagnosed bladder carcinoma in situ (CIS).


METHODS
A total of 55 BCG-naive patients with bladder CIS were randomized to receive bropirimine (n = 27) or BCG (n = 28). Bropirimine was orally administered at a dose of 3 g/day for 3 consecutive days with a 4-day drug-free interval for up to 1 year. BCG-Tice instillations were administered weekly for 2 x 6 weeks. Both biopsies and cytology had to be negative for the patient to be considered a complete responder (CR).


RESULTS
The percentage of dropouts for all of the adverse events was 4% for bropirimine and 14% for BCG. The most frequently reported local events in the bropirimine- versus the BCG-treated group were irritative complaints, 64 vs. 89% (p = 0.03) and hematuria, 24 vs. 61% (p < 0.01). The most frequently reported systemic events in the bropirimine- versus the BCG-treated group were fever 4 vs. 21%, flu syndrome 24 vs. 7%, headache 28 vs. 11% and nausea 24 vs. 11% (all p > 0.05). A total of 92% of the patients treated with bropirimine had a CR with a mean duration of 12.6 months (95% CI 9.2-15.9). In the BCG group, all of the patients had a CR with a mean of 12.3 months (95% CI 8.5-16.0).


CONCLUSIONS
This study shows that bropirimine, an orally administered drug that can be self-administered to outpatients with more acceptable local toxicity compared to BCG, could be an effective first-line therapy in patients with CIS of the urinary bladder. Continued investigation of bropirimine is warranted to increase its clinical utility.
Witjes
W P
WP
Department of Urology, University Hospital Nijmegen, The Netherlands. w.witjes@trial.azn.nl
König
M
M
Boeminghaus
F P
FP
Hall
R R
RR
Schulman
C C
CC
Zurlo
M
M
Fittipaldo
A
A
Riggi
M
M
Debruyne
F M
FM
D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000627:therapeutic use*; D000284:Administration, Oral; D001500:BCG Vaccine / Q000009:adverse effects / Q000627:therapeutic use*; D002278:Carcinoma in Situ / Q000628:therapy*; D016009:Chi-Square Distribution; D003596:Cytosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D015996:Survival Rate; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000628:therapy*
D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D003596:Cytosine; C033560:bropirimine