Bi-213-anti-EGFR-MAb therapy of recurrent bladder cancer

Ziel/Aim: Following transurethral resection of non-muscle-invasive bladder cancer (carcinoma in situ, CIS) and subsequent chemotherapy and treatment with Bacillus Calmette–Guérin (BCG), up to 40% of patients relapse within 5 years and need complete bladder excision. 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 feasibility, safety and therapeutic efficacy of an alpha-emitter radioimmunoconjugate in recurrent bladder cancer patients. Methodik/Methods: The alpha-emitter Bi-213 was eluted from a Ac-225/Bi-213 generator system and coupled to the anti-EGFR-MAb (cetuximab, Merck, Germany) via the chelating agent CHX-A”-DTPA. 12 patients (10 m, 2 f) suffering from CIS bladder cancer that had shown no response to BCG treatment were intravesically applied with 366-821 MBq (9.9 – 22.2 mCi) 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 up to 120 min after injection. Efficacy was evaluated via endoscopy and histology after eight weeks, and then six-monthly. Ergebnisse/Results: All patients (pts) showed excellent tolerance of the treatment without any side effects. SPECT/CT monitoring clearly revealed location of the Bi-213-anti-EGFR-MAb immunoconjugate in the bladder. Up to now (12 pts, 13 treatments), treatment resulted in a documented complete eradication of tumor cells in four patients (CR lasting 44+, resp. 30+ months, 1 CR lasting 15 months, 1 CR after 2nd therapy 6+months) and remaining / progressive tumor growth in eight patients. Schlussfolgerungen/Conclusions: Intravesical instillation of Bi-213-anti-EGFR-MAb is a promising, well tolerated therapeutic option for treatment of in situ bladder cancer after BCG failure and can help to avoid or postpone radical bladder surgery. Repeated instillation seems to be possible; a follow up study is planned to investigate further improvement of therapeutic efficacy through dose escalation and repeated treatments.JRC.G.I.5-Advanced Nuclear Knowledg

Bi-213-anti-EGFR-MAb therapy of recurrent bladder cancer – a pilot study

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 and need complete bladder excision. 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 feasibility, safety and therapeutic efficacy of the α-emitter radioimmunoconjugate in recurrent bladder cancer patients.JRC.G.I.5-Advanced Nuclear Knowledg

Treatment of carcinoma in situ of the urinary bladder with an alpha-emitter immunoconjugate targeting the epidermal growth factor receptor: A pilot study

Purpose: 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. Methods: 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. Results: 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. Conclusion: 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.JRC.G.I.5-Advanced Nuclear Knowledg