First intravesical α-radioimmunotherapy of human urothelial carcinoma in men as a new therapy for carcinoma in situ after BCG failure.

Abstract

427 Background: Failure to respond to BCG in patients with carcinoma in situ (CIS) of the urinary bladder is problematic, since those tumours often have the potential to progress to muscle invasion. radical cystectomy remains the mainstay after BCG failure.Because treatment of mice bearing intravesical human bladder cancer xenografts with Bi-213-anti-EGFR-MAb turned out highly efficient (Pfost B et al. 2009, J of Nucl Med 50:1700-1708), the aim of this pilot study was to evaluate tolerability and safety of the α-emitter radioimmunoconjugate in patients after BCG failure. Methods: The alpha-emitter Bi-213 was eluted from a generator system provided by the Institute for Transuranium Elements (European Commission, JRC, Karlsruhe, Germany) and coupled to the anti-EGFR-mAb (Cetuximab, Merck, Germany) via the chelating agent CHX-A”-DTPA. 7 patients suffering from carcinoma in situ of the bladder who had histologically proven residual tumor after BCG induction therapy were included. After emptying the bladder an activity between 9,9 mCi and 22,2 mCi in 40 ml NaCl of Bi-213-anti-EGFR-mAb via a transurethral catheter was instilled. Distribution of Bi-213-anti-EGFR-mAb was monitored by SPECT/CT. Treatment was terminated by emptying of the radioimmunoconjugate from the bladder 120 min after injection. Efficacy was evaluated via endoscopy and histology six weeks after instillation. Results: All patients showed excellent toleration of the treatment without any side effects. SPECT/CT monitoring clearly revealed location of the Bi-213-anti-EGFR-MAb immunoconjugate only in the bladder without extravasation. Treatment resulted in complete eradication of tumor cells in 3 patients and persistent tumor detection in the other 4 patients. Conclusions: Intravesical instillation of Bi-213-anti-EGFR-mAb is a promising therapeutic option for treatment of in situ bladder cancerafterBCG failure for patients who wish to preserve the bladder.