Oral bropirimine immunotherapy of bladder carcinoma in situ after prior intravesical bacille Calmette-Guérin

• Published in: Urology (Ridgewood, N.J.) Vol. 51; no. 2; pp. 226 - 231
• Main Authors: Sarosdy, Michael F., Manyak, Michael J., Sagalowsky, Arthur I., Belldegrun, Arie, Benson, Mitchell C., Bihrle, William, Carroll, Peter R., Ellis, William J., Hudson, M'Liss A., Sharkey, Francis E.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.02.1998; Elsevier Science
• Subjects: Adjuvants, Immunologic - adverse effects; Adjuvants, Immunologic - therapeutic use; Administration, Oral; Antineoplastic agents; BCG Vaccine - adverse effects; BCG Vaccine - therapeutic use; Biological and medical sciences; Carcinoma in Situ - drug therapy; Cytosine - administration & dosage; Cytosine - adverse effects; Cytosine - analogs & derivatives; Humans; Immunotherapy; Medical sciences; Pharmacology. Drug treatments; Remission Induction; Treatment Failure; Urinary Bladder Neoplasms - drug therapy; Antineoplastic agent; Human; Urinary system disease; Carcinoma; Carcinoma in situ; BCG; Oral administration; Bropirimine; Malignant tumor; Urinary tract disease; Treatment; Urinary bladder; Immunotherapy; Bladder disease; Intravesical administration
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/S0090-4295(97)00510-4

Objectives. Bropirimine is an oral immunomodulator that has demonstrated anticancer activity in transitional cell carcinoma in situ (CIS) in both the bladder and upper urinary tract. Activity also has been documented in patients after prior therapy with bacille Calmette-Guérin (BCG). To more accurately estimate bropirimine's efficacy in BCG-resistant bladder CIS, a Phase II trial was performed. A separate analysis was performed in additional patients intolerant of BCG toxicity. Methods. Patients received bropirimine 3.0 g/day by mouth for 3 consecutive days, weekly, for up to 1 year. Bladder biopsies and cytologic examination were performed quarterly. Complete response (CR) required negative biopsy and cytology results. Results. Twenty-one of 86 patients entered were not evaluable. CR was seen in 21 (32%; 95th percentile confidence interval [CI], 21% to 44%) of 65 evaluable patients, including 14 (30%, CI 17% to 43%) of 47 BCG-resistant, and 7 (39%, CI 16% to 61%) of 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 (median 12) BCG treatments; intolerant patients had received 4 to 11 treatments (median 6). Response duration ranged from 65 to 810 days, with median not yet reached (but greater than 12 months). Thirteen (15%) of 86 stopped bropirimine due to toxicity. Progression to invasive or metastatic disease during or immediately after therapy was documented in only 4 patients (6%), all nonresponders. Conclusions. Bropirimine may be an alternative to cystectomy for some patients with bladder CIS who have failed or have not tolerated BCG. Further evaluation to improve responses and durability is warranted.