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.

SCHEIDHAUER Klemens;  SEIDL C.;  AUTENRIETH M.;  BRUCHERTSEIFER Frank;  APOSTOLIDIS Christos;  KURTZ F;  HORN Thomas;  PFOB C;  SCHWAIGER M.;  GSCHWEND J.E.;  D'ALESSANDRIA C;  MORGENSTERN Alfred; 

2018-05-28

SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN

JRC111736

0029-5566,   

http://www.nuklearmedizin.de/jahrestagungen/abstr_online2018/abstract_detail.php?navId=216&aId=282,    https://publications.jrc.ec.europa.eu/repository/handle/JRC111736,