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

Michael F. Sarosdy, Michael J. Manyak, Arthur I Sagalowsky, Arie Belldegrun, Mitchell C. Benson, William Bihrle, Peter R. Carroll, William J. Ellis, M'Liss A. Hudson, Francis E. Sharkey

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Abstract

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-Guerin (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.

Original languageEnglish (US)
Pages (from-to)226-231
Number of pages6
JournalUrology
Volume51
Issue number2
DOIs
StatePublished - Feb 1998

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Carcinoma in Situ
Immunotherapy
Urinary Bladder
Confidence Intervals
bropirimine
Biopsy
Transitional Cell Carcinoma
Cystectomy
Immunologic Factors
Therapeutics
Urinary Tract
Cell Biology
Mouth
Recurrence

ASJC Scopus subject areas

  • Urology

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Sarosdy, M. F., Manyak, M. J., Sagalowsky, A. I., Belldegrun, A., Benson, M. C., Bihrle, W., ... Sharkey, F. E. (1998). Oral bropirimine immunotherapy of bladder carcinoma in situ after prior intravesical bacille Calmette-Guerin. Urology, 51(2), 226-231. https://doi.org/10.1016/S0090-4295(97)00510-4

Oral bropirimine immunotherapy of bladder carcinoma in situ after prior intravesical bacille Calmette-Guerin. / 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.

In: Urology, Vol. 51, No. 2, 02.1998, p. 226-231.

Research output: Contribution to journalArticle

Sarosdy, MF, Manyak, MJ, Sagalowsky, AI, Belldegrun, A, Benson, MC, Bihrle, W, Carroll, PR, Ellis, WJ, Hudson, MLA & Sharkey, FE 1998, 'Oral bropirimine immunotherapy of bladder carcinoma in situ after prior intravesical bacille Calmette-Guerin', Urology, vol. 51, no. 2, pp. 226-231. https://doi.org/10.1016/S0090-4295(97)00510-4
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. / Oral bropirimine immunotherapy of bladder carcinoma in situ after prior intravesical bacille Calmette-Guerin. In: Urology. 1998 ; Vol. 51, No. 2. pp. 226-231.
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abstract = "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-Guerin (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.",
author = "Sarosdy, {Michael F.} and Manyak, {Michael J.} and Sagalowsky, {Arthur I} and Arie Belldegrun and Benson, {Mitchell C.} and William Bihrle and Carroll, {Peter R.} and Ellis, {William J.} and Hudson, {M'Liss A.} and Sharkey, {Francis E.}",
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T1 - Oral bropirimine immunotherapy of bladder carcinoma in situ after prior intravesical bacille Calmette-Guerin

AU - Sarosdy, Michael F.

AU - Manyak, Michael J.

AU - Sagalowsky, Arthur I

AU - Belldegrun, Arie

AU - Benson, Mitchell C.

AU - Bihrle, William

AU - Carroll, Peter R.

AU - Ellis, William J.

AU - Hudson, M'Liss A.

AU - Sharkey, Francis E.

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N2 - 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-Guerin (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.

AB - 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-Guerin (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.

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