Efficacy and safety of valrubicin for the treatment of bacillus Calmette-Guerin refractory carcinoma in situ of the bladder

Gary Steinberg, Robert Bahnson, Stanley Brosman, Richard Middleton, Zev Wajsman, Michael Wehle, Stephen Auerbach, Michael Blute, William Bohnert, Charles Brendler, Paul Bretton, Thomas Brown, John Byrne, Jeffrey Cohen, Bruce Dalkin, Jeoffrey Deeths, Eugena Dula, William Ellis, Howard Epstein, Robert FeldmanWilliam Friedel, Donald Gleason, Richard Greenberg, Thomas Hakala, John Heaney, Jeffrey Ignatoff, Mark Immergut, Charles Jackson, Charles F. Johnson, Aaron Katz, Eric Klein, Ira Klimberg, Bruce Lowe, William Moseley, Myron Murdock, Perinchery Narayan, Edmund Sabanegh, Joseph Schmidt, Michael Schutz, Mark Soloway, John Tuttle, Zevs Wajsman, Lamar Weems, Michael Wehe, Timothy Wilson, Norman Zinner

Research output: Contribution to journalArticle

210 Citations (Scopus)

Abstract

Purpose: We assess the efficacy and safety of intravesical valrubicin for the treatment of carcinoma in situ in patients with failure or recurrence after bacillus Calmette-Guerin (BCG) and who otherwise would have undergone cystectomy. Total anthracycline recovery in urine samples obtained within 24 hours of valrubicin administration was assessed in a subset of patients. Materials and Methods: A total of 90 patients with recurrent carcinoma in situ after failed multiple prior courses of intravesical therapy, including at least i course of BCG, participated in this open label, noncomparative study. Each patient received 6 weekly instillations of 800 mg. intravesical valrubicin. Disease evaluations were made at baseline and 3-month intervals following treatment. Evaluations included cystoscopy with biopsy and urine cytology. Toxicity was noted throughout treatment and followup. No evidence of disease recurrence for 6 months or greater was considered a complete response. Results: Of 90 patients 19 (21%) had a complete response, including 7 who remained disease-free at the last evaluation, with a median followup of 30 months. Additionally, 14 patients who did not meet the strict protocol definition of complete response had superficial Ta disease only. Median time to failure and/or last followup for complete responders was greater than 18 months. Recurrence has been noted in 79 patients to date, including only 2 with clinically advanced disease (stage T2). Of these 79 patients 44 (56%, 4 responders and 40 nonresponders) underwent radical cystectomy. Of the 41 patients with known pathological stage 6 (15%) had stage pT3 or greater at cystectomy. Four patients died of bladder cancer during the median followup of 30 months, none of whom was a complete responder or underwent cystectomy following valrubicin. The main side effects of valrubicin therapy were reversible local bladder symptoms. Conclusions: Valrubicin was effective and well tolerated in patients with carcinoma in situ of the bladder refractory to BCG therapy. Delaying cystectomy while attempting salvage therapy with valrubicin does not pose an undue risk to most patients.

Original languageEnglish
Pages (from-to)761-767
Number of pages7
JournalJournal of Urology
Volume163
Issue number3
StatePublished - Mar 1 2000
Externally publishedYes

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valrubicin
Carcinoma in Situ
Mycobacterium bovis
Urinary Bladder
Safety
Cystectomy
Therapeutics
Recurrence
Urine

Keywords

  • Bladder
  • Bladder neoplasms
  • Carcinoma in situ
  • Drug
  • Instillation

ASJC Scopus subject areas

  • Urology

Cite this

Steinberg, G., Bahnson, R., Brosman, S., Middleton, R., Wajsman, Z., Wehle, M., ... Zinner, N. (2000). Efficacy and safety of valrubicin for the treatment of bacillus Calmette-Guerin refractory carcinoma in situ of the bladder. Journal of Urology, 163(3), 761-767.

Efficacy and safety of valrubicin for the treatment of bacillus Calmette-Guerin refractory carcinoma in situ of the bladder. / Steinberg, Gary; Bahnson, Robert; Brosman, Stanley; Middleton, Richard; Wajsman, Zev; Wehle, Michael; Auerbach, Stephen; Blute, Michael; Bohnert, William; Brendler, Charles; Bretton, Paul; Brown, Thomas; Byrne, John; Cohen, Jeffrey; Dalkin, Bruce; Deeths, Jeoffrey; Dula, Eugena; Ellis, William; Epstein, Howard; Feldman, Robert; Friedel, William; Gleason, Donald; Greenberg, Richard; Hakala, Thomas; Heaney, John; Ignatoff, Jeffrey; Immergut, Mark; Jackson, Charles; Johnson, Charles F.; Katz, Aaron; Klein, Eric; Klimberg, Ira; Lowe, Bruce; Moseley, William; Murdock, Myron; Narayan, Perinchery; Sabanegh, Edmund; Schmidt, Joseph; Schutz, Michael; Soloway, Mark; Tuttle, John; Wajsman, Zevs; Weems, Lamar; Wehe, Michael; Wilson, Timothy; Zinner, Norman.

In: Journal of Urology, Vol. 163, No. 3, 01.03.2000, p. 761-767.

Research output: Contribution to journalArticle

Steinberg, G, Bahnson, R, Brosman, S, Middleton, R, Wajsman, Z, Wehle, M, Auerbach, S, Blute, M, Bohnert, W, Brendler, C, Bretton, P, Brown, T, Byrne, J, Cohen, J, Dalkin, B, Deeths, J, Dula, E, Ellis, W, Epstein, H, Feldman, R, Friedel, W, Gleason, D, Greenberg, R, Hakala, T, Heaney, J, Ignatoff, J, Immergut, M, Jackson, C, Johnson, CF, Katz, A, Klein, E, Klimberg, I, Lowe, B, Moseley, W, Murdock, M, Narayan, P, Sabanegh, E, Schmidt, J, Schutz, M, Soloway, M, Tuttle, J, Wajsman, Z, Weems, L, Wehe, M, Wilson, T & Zinner, N 2000, 'Efficacy and safety of valrubicin for the treatment of bacillus Calmette-Guerin refractory carcinoma in situ of the bladder', Journal of Urology, vol. 163, no. 3, pp. 761-767.
Steinberg G, Bahnson R, Brosman S, Middleton R, Wajsman Z, Wehle M et al. Efficacy and safety of valrubicin for the treatment of bacillus Calmette-Guerin refractory carcinoma in situ of the bladder. Journal of Urology. 2000 Mar 1;163(3):761-767.
Steinberg, Gary ; Bahnson, Robert ; Brosman, Stanley ; Middleton, Richard ; Wajsman, Zev ; Wehle, Michael ; Auerbach, Stephen ; Blute, Michael ; Bohnert, William ; Brendler, Charles ; Bretton, Paul ; Brown, Thomas ; Byrne, John ; Cohen, Jeffrey ; Dalkin, Bruce ; Deeths, Jeoffrey ; Dula, Eugena ; Ellis, William ; Epstein, Howard ; Feldman, Robert ; Friedel, William ; Gleason, Donald ; Greenberg, Richard ; Hakala, Thomas ; Heaney, John ; Ignatoff, Jeffrey ; Immergut, Mark ; Jackson, Charles ; Johnson, Charles F. ; Katz, Aaron ; Klein, Eric ; Klimberg, Ira ; Lowe, Bruce ; Moseley, William ; Murdock, Myron ; Narayan, Perinchery ; Sabanegh, Edmund ; Schmidt, Joseph ; Schutz, Michael ; Soloway, Mark ; Tuttle, John ; Wajsman, Zevs ; Weems, Lamar ; Wehe, Michael ; Wilson, Timothy ; Zinner, Norman. / Efficacy and safety of valrubicin for the treatment of bacillus Calmette-Guerin refractory carcinoma in situ of the bladder. In: Journal of Urology. 2000 ; Vol. 163, No. 3. pp. 761-767.
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abstract = "Purpose: We assess the efficacy and safety of intravesical valrubicin for the treatment of carcinoma in situ in patients with failure or recurrence after bacillus Calmette-Guerin (BCG) and who otherwise would have undergone cystectomy. Total anthracycline recovery in urine samples obtained within 24 hours of valrubicin administration was assessed in a subset of patients. Materials and Methods: A total of 90 patients with recurrent carcinoma in situ after failed multiple prior courses of intravesical therapy, including at least i course of BCG, participated in this open label, noncomparative study. Each patient received 6 weekly instillations of 800 mg. intravesical valrubicin. Disease evaluations were made at baseline and 3-month intervals following treatment. Evaluations included cystoscopy with biopsy and urine cytology. Toxicity was noted throughout treatment and followup. No evidence of disease recurrence for 6 months or greater was considered a complete response. Results: Of 90 patients 19 (21{\%}) had a complete response, including 7 who remained disease-free at the last evaluation, with a median followup of 30 months. Additionally, 14 patients who did not meet the strict protocol definition of complete response had superficial Ta disease only. Median time to failure and/or last followup for complete responders was greater than 18 months. Recurrence has been noted in 79 patients to date, including only 2 with clinically advanced disease (stage T2). Of these 79 patients 44 (56{\%}, 4 responders and 40 nonresponders) underwent radical cystectomy. Of the 41 patients with known pathological stage 6 (15{\%}) had stage pT3 or greater at cystectomy. Four patients died of bladder cancer during the median followup of 30 months, none of whom was a complete responder or underwent cystectomy following valrubicin. The main side effects of valrubicin therapy were reversible local bladder symptoms. Conclusions: Valrubicin was effective and well tolerated in patients with carcinoma in situ of the bladder refractory to BCG therapy. Delaying cystectomy while attempting salvage therapy with valrubicin does not pose an undue risk to most patients.",
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author = "Gary Steinberg and Robert Bahnson and Stanley Brosman and Richard Middleton and Zev Wajsman and Michael Wehle and Stephen Auerbach and Michael Blute and William Bohnert and Charles Brendler and Paul Bretton and Thomas Brown and John Byrne and Jeffrey Cohen and Bruce Dalkin and Jeoffrey Deeths and Eugena Dula and William Ellis and Howard Epstein and Robert Feldman and William Friedel and Donald Gleason and Richard Greenberg and Thomas Hakala and John Heaney and Jeffrey Ignatoff and Mark Immergut and Charles Jackson and Johnson, {Charles F.} and Aaron Katz and Eric Klein and Ira Klimberg and Bruce Lowe and William Moseley and Myron Murdock and Perinchery Narayan and Edmund Sabanegh and Joseph Schmidt and Michael Schutz and Mark Soloway and John Tuttle and Zevs Wajsman and Lamar Weems and Michael Wehe and Timothy Wilson and Norman Zinner",
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T1 - Efficacy and safety of valrubicin for the treatment of bacillus Calmette-Guerin refractory carcinoma in situ of the bladder

AU - Steinberg, Gary

AU - Bahnson, Robert

AU - Brosman, Stanley

AU - Middleton, Richard

AU - Wajsman, Zev

AU - Wehle, Michael

AU - Auerbach, Stephen

AU - Blute, Michael

AU - Bohnert, William

AU - Brendler, Charles

AU - Bretton, Paul

AU - Brown, Thomas

AU - Byrne, John

AU - Cohen, Jeffrey

AU - Dalkin, Bruce

AU - Deeths, Jeoffrey

AU - Dula, Eugena

AU - Ellis, William

AU - Epstein, Howard

AU - Feldman, Robert

AU - Friedel, William

AU - Gleason, Donald

AU - Greenberg, Richard

AU - Hakala, Thomas

AU - Heaney, John

AU - Ignatoff, Jeffrey

AU - Immergut, Mark

AU - Jackson, Charles

AU - Johnson, Charles F.

AU - Katz, Aaron

AU - Klein, Eric

AU - Klimberg, Ira

AU - Lowe, Bruce

AU - Moseley, William

AU - Murdock, Myron

AU - Narayan, Perinchery

AU - Sabanegh, Edmund

AU - Schmidt, Joseph

AU - Schutz, Michael

AU - Soloway, Mark

AU - Tuttle, John

AU - Wajsman, Zevs

AU - Weems, Lamar

AU - Wehe, Michael

AU - Wilson, Timothy

AU - Zinner, Norman

PY - 2000/3/1

Y1 - 2000/3/1

N2 - Purpose: We assess the efficacy and safety of intravesical valrubicin for the treatment of carcinoma in situ in patients with failure or recurrence after bacillus Calmette-Guerin (BCG) and who otherwise would have undergone cystectomy. Total anthracycline recovery in urine samples obtained within 24 hours of valrubicin administration was assessed in a subset of patients. Materials and Methods: A total of 90 patients with recurrent carcinoma in situ after failed multiple prior courses of intravesical therapy, including at least i course of BCG, participated in this open label, noncomparative study. Each patient received 6 weekly instillations of 800 mg. intravesical valrubicin. Disease evaluations were made at baseline and 3-month intervals following treatment. Evaluations included cystoscopy with biopsy and urine cytology. Toxicity was noted throughout treatment and followup. No evidence of disease recurrence for 6 months or greater was considered a complete response. Results: Of 90 patients 19 (21%) had a complete response, including 7 who remained disease-free at the last evaluation, with a median followup of 30 months. Additionally, 14 patients who did not meet the strict protocol definition of complete response had superficial Ta disease only. Median time to failure and/or last followup for complete responders was greater than 18 months. Recurrence has been noted in 79 patients to date, including only 2 with clinically advanced disease (stage T2). Of these 79 patients 44 (56%, 4 responders and 40 nonresponders) underwent radical cystectomy. Of the 41 patients with known pathological stage 6 (15%) had stage pT3 or greater at cystectomy. Four patients died of bladder cancer during the median followup of 30 months, none of whom was a complete responder or underwent cystectomy following valrubicin. The main side effects of valrubicin therapy were reversible local bladder symptoms. Conclusions: Valrubicin was effective and well tolerated in patients with carcinoma in situ of the bladder refractory to BCG therapy. Delaying cystectomy while attempting salvage therapy with valrubicin does not pose an undue risk to most patients.

AB - Purpose: We assess the efficacy and safety of intravesical valrubicin for the treatment of carcinoma in situ in patients with failure or recurrence after bacillus Calmette-Guerin (BCG) and who otherwise would have undergone cystectomy. Total anthracycline recovery in urine samples obtained within 24 hours of valrubicin administration was assessed in a subset of patients. Materials and Methods: A total of 90 patients with recurrent carcinoma in situ after failed multiple prior courses of intravesical therapy, including at least i course of BCG, participated in this open label, noncomparative study. Each patient received 6 weekly instillations of 800 mg. intravesical valrubicin. Disease evaluations were made at baseline and 3-month intervals following treatment. Evaluations included cystoscopy with biopsy and urine cytology. Toxicity was noted throughout treatment and followup. No evidence of disease recurrence for 6 months or greater was considered a complete response. Results: Of 90 patients 19 (21%) had a complete response, including 7 who remained disease-free at the last evaluation, with a median followup of 30 months. Additionally, 14 patients who did not meet the strict protocol definition of complete response had superficial Ta disease only. Median time to failure and/or last followup for complete responders was greater than 18 months. Recurrence has been noted in 79 patients to date, including only 2 with clinically advanced disease (stage T2). Of these 79 patients 44 (56%, 4 responders and 40 nonresponders) underwent radical cystectomy. Of the 41 patients with known pathological stage 6 (15%) had stage pT3 or greater at cystectomy. Four patients died of bladder cancer during the median followup of 30 months, none of whom was a complete responder or underwent cystectomy following valrubicin. The main side effects of valrubicin therapy were reversible local bladder symptoms. Conclusions: Valrubicin was effective and well tolerated in patients with carcinoma in situ of the bladder refractory to BCG therapy. Delaying cystectomy while attempting salvage therapy with valrubicin does not pose an undue risk to most patients.

KW - Bladder

KW - Bladder neoplasms

KW - Carcinoma in situ

KW - Drug

KW - Instillation

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