Phase II study of intravesical therapy with AD32 in patients with papillary urothelial carcinoma or carcinoma in situ (CIS) refractory to prior therapy with bacillus Calmette-Guerin (E3897): A trial of the Eastern Cooperative Oncology Group

Ignatoff, Jeffrey M.; Chen, Yu-Hui; Greenberg, Richard Evan; Pow-Sang, Julio M.; Messing, Edward M.; Wilding, George

doi:10.1016/j.urolonc.2008.05.004

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Volume 27, Issue 5 , Pages 496-501, September 2009

Phase II study of intravesical therapy with AD32 in patients with papillary urothelial carcinoma or carcinoma in situ (CIS) refractory to prior therapy with bacillus Calmette-Guerin (E3897): A trial of the Eastern Cooperative Oncology Group☆

Received 8 February 2008; received in revised form 11 May 2008; accepted 13 May 2008. published online 22 July 2008.

Abstract

Objective

To assess the safety and effectiveness of AD32, a doxorubicin analogue with little systemic exposure when administered intravesically, in patients with recurrent or refractory superficial urothelial carcinoma (formerly called transitional cell carcinoma [TCC]), or carcinoma in situ (CIS), who have failed prior BCG-based immunotherapy.

Methods

Eligible patients received six weekly doses (800 mg) of intravesical AD32 and were evaluated at 12-week intervals for 24 months or until date of worsening disease. Primary analysis was the proportion of all patients recurrence-free at 12 months. Treatment-related and GU-specific toxicities were also examined. All participating institutions submitted the protocol for Institutional Review Board (IRB) approval.

Results

The study was halted due to unavailability of study drug after accrual of 48 of a planned 64 patients; 42 were included in the analysis. Of these, 28 (67%) were still alive after median follow-up of 61.1 months. Of 21 TCC patients, 18 (85.7%) experienced disease recurrence (median time to recurrence, 5.3 months). Of the 5 CIS patients with complete response (CR), 3 (60%) experienced disease recurrence; (median time to recurrence, 37.3 months). Recurrence-free rates at 12 and 24 months were 20% (90% CI, 7.8%, 36.1%) and 15% (90 CI, 4.9%, 30.2%), respectively, for patients with TCC and 80% (90% CI, 31.4%, 95.8%) at both intervals for CIS patients with CR. Infection was the most common treatment-related toxicity; no grade 4 or higher toxicity was observed. The most common GU-specific toxicity was increased frequency/urgency.

Conclusions

AD32 is safe and active for treatment of recurrent or refractory superficial bladder carcinoma. The agent awaits more complete characterization when drug production problems can be solved.

Keywords: AD32, Superficial transitional cell carcinoma, Urothelial carcinoma, Carcinoma in situ, Bladder, Intravesical

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☆ This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M.D.) and supported in part by Public Health Service grants CA23318, CA66636, CA21115, CA27525, CA11083, CA17145, CA21076 and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.