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Ignatoff JM , Chen YH , Greenberg RE , Pow-Sang JM , Messing EM , Wilding G
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
Urologic Oncology-Seminars and Original Investigations. 2009 Sep-Oct;27(5) :496-501
PMID: 18639470    PMCID: PMC2743955   
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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. AM 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% Cl, 7.8%, 36.1%) and 15% (90 Cl, 4.9% 30.2%), respectively, for patients with TCC and 80% (90% Cl, 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. (C) 2009 Elsevier Inc. All rights reserved.
Notes
Ignatoff, Jeffrey A. Chen, Yu-Hui Greenberg, Richard Evan Pow-Sang, Julio M. Messing, Edward M. Wilding, George Public Health Service [CA23318, CA66636, CA21115, CA27525, CA11083, CA17145, CA21076]; National Cancer Institute, National Institutes of Health ; Department of Health and Human Services 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 die responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. 26 Elsevier science inc; 360 park ave south, new york, ny 10010-1710 usa 494mf