Treatment of bladder cancer with Bi-213-anti-EGFR-MAb - A pilot study

Objectives Following transurethral resection of non-muscle-invasive bladder cancer (carcinoma in situ) and subsequent chemotherapy and treatment with Bacillus Calmette-Guérin (BCG), up to 40% of patients relapse within 5 years. Therefore, new therapeutic strategies to combat tumor recurrence are needed. Because treatment of mice bearing intravesical human bladder cancer xenografts with Bi-213-anti-EGFR-MAb turned out highly efficient, the aim of this pilot study was to evaluate therapeutic efficacy of the α-emitter radioimmunoconjugate in bladder cancer patients.

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. Two patients suffering from carcinoma in situ bladder cancer that had shown no response to BCG treatment were intravesically applied with 370 MBq of Bi-213-anti-EGFR-MAb in 40 ml of PBS. 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 after six weeks.

Results Both 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 in the bladder. Treatment resulted in complete eradication of tumor cells in one patient and progressive tumor growth in the other patient.

Conclusions Intravesical instillation of Bi-213-anti-EGFR-MAb is a promising therapeutic option for treatment of in situ bladder cancer after BCG failure.