ORAL BROPIRIMINE IMMUNOTHERAPY OF BLADDER-CARCINOMA IN-SITU AFTER PRIOR INTRAVESICAL BACILLE-CALMETTE-GUERIN

Objectives. Bropirimine is an oral immunomodulator that has demonstrat ed anticancer activity in transitional cell carcinoma in situ (CIS) in both the bladder and upper urinary tract. Activity also has been docu mented in patients after prior therapy with bacille Calmette-Guerin (B CG). To more accurately estimate bropirimine's efficacy in BCG-resista nt bladder CIS, a Phase II trial was performed. A separate analysis wa s performed in additional patients intolerant of BCG toxicity. Methods . Patients received bropirimine 3.0 g/day by mouth for 3 consecutive d ays, weekly, for up to 1 year. Bladder biopsies and cytologic examinat ion were performed quarterly. Complete response (CR) required negative biopsy and cytology results. Results. Twenty-one of 86 patients enter ed were not evaluable. CR was seen in 21 (32%; 95th percentile confide nce interval [CI], 21% to 44%) of 65 evaluable patients, including 14 (30%, CI 17% to 43%) of 47 BCC-resistant, and 7 (39%, CI 16% to 61%) o f 18 BCG-intolerant patients. Overall, by intent-to-treat analysis, CR was thus seen in 21 (24%) of 86 subjects. Most BCG-resistant patients were failures to BCG without relapse, and had received 12 to 36 (medi an 12) BCG treatments; intolerant patients had received 4 to 11 treatm ents (median 6). Response duration ranged from 65 to 810 days, with me dian not yet reached (but greater than 12 months). Thirteen (15%) of 8 6 stopped bropirimine due to toxicity. Progression to invasive or meta static disease during or immediately after therapy was documented in o nly 4 patients (6%), all nonresponders. Conclusions. Bropirimine may b e an alternative to cystectomy for some patients with bladder CIS who have failed or have not tolerated BCC. Further evaluation to improve r esponses and durability is warranted. (C) 1998, Elsevier Science Inc. All rights reserved.