Treatment of carcinoma in situ of the urinary bladder with an alpha-emitter immunoconjugate targeting the epidermal growth factor receptor: a pilot study
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Patients with carcinoma in situ (CIS) of the bladder refractory to bacillus Calmette-Guérin (BCG) treatment are usually treated with cystectomy. Therefore, new treatment options with preservation of the urinary bladder are needed. The objective of the study was to investigate the feasibility, safety and efficacy of a novel targeted alpha-emitter immunotherapy for CIS after BCG treatment failure.
A pilot study was conducted in 12 patients (age range 64–86 years, ten men, two women) with biopsy-proven CIS of the bladder refractory to BCG treatment. The patients were treated intravesically with a single instillation (one patient was treated twice) of the alpha-emitter 213Bi coupled to an anti-EGFR antibody (366–821 MBq). The primary aims of the study were to determine the feasibility of treatment with the 213Bi-immunoconjugate and evaluation of adverse effects. Therapeutic efficacy was monitored by histological mapping of the urinary bladder 8 weeks after treatment and at different time points thereafter.
The study proved that intravesical instillation of the 213Bi-immunoconjugate targeting EGFR is feasible. No adverse effects were observed and all blood and urine parameters determined remained in their normal ranges. Therapeutic efficacy was considered satisfactory, in that three of the 12 patients showed no signs of CIS 44, 30 and 3 months after treatment.
Intravesical instillation of 213Bi-anti-EGFR monoclonal antibody was well tolerated and showed therapeutic efficacy. Repeated instillation and/or instillation of higher activities of the 213Bi-immunoconjugate might lead to better therapeutic outcomes. A phase I clinical trial is planned.
KeywordsAlpha-emitter 213Bi 225Ac/213Bi generator Targeted therapy Bladder cancer Feasibility Adverse effects Therapeutic efficacy
We owe special thanks to Reingard Senekowitsch-Schmidtke who introduced treatment of bladder cancer xenografts with 213Bi-anti-EGFR immunoconjugates to the scientific community. The authors are indebted for provision of parts of the 225Ac/213Bi used in this study to the Isotope Development and Production for Research and Applications Program, Office of Nuclear Physics, U.S. Department of Energy.
Compliance with ethical standards
Conflicts of interest
The study was approved by the local Ethics Committee.
Informed consent was obtained from all patients included in the study.
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