A review of clinical studies of bropirimine immunotherapy of carcinoma in situ of the bladder and upper urinary tract.

Bropirimine has been shown to have activity against carcinoma in situ (CIS) of the bladder in a previous phase-I trial. A review of three completed clinical trials as well as ongoing studies is presented to provide a current update. Details of the initial phase-I trial are reviewed, as are findings of a subsequent phase-II trial in bladder CIS and a multicenter study in upper tract CIS. All have used a dose of 3 g/day for 3 consecutive days each week, repeated weekly for up to 1 year. Cytology must be positive prior to treatment, and both biopsies and cytology must be negative after therapy for the patient to be considered a complete response. In the phase-II trial in bladder CIS, 20 (61%) of 33 patients had a complete response. Responders included patients with prior bacillus Calmette-Guérin (BCG) therapy, uni- and multifocal CIS, and primary and secondary CIS. Responses were seen in 10 (48%) of 21 evaluable patients with upper tract CIS. Toxicities in both studies were manageable in most patients. Trials underway include bropirimine in BCG-failed CIS, a randomized comparison to BCG in previously untreated patients, and a trial of the two together. Bropirimine does have activity against both bladder and upper tract CIS on the dose schedule used to date.