The application of adjuvant autologous antravesical macrophage cell therapy vs. BCG in non-muscle invasive bladder cancer: a multicenter, randomized trial.

Introduction: While adjuvant immunotherapy with Bacille Calmette Guérin (BCG) is effective in non-muscle-invasive bladder cancer (BC), adverse events (AEs) are considerable. Monocyte-derived activated killer cells (MAK) are discussed as essential in antitumoural immunoresponse, but their application may imply risks. The present trial compared autologous intravesical macrophage cell therapy (BEXIDEM) to BCG in patients after transurethral resection (TURB) of BC.

Materials And Methods: This open-label trial included 137 eligible patients with TaG1-3, T1G1-2 plurifocal or unifocal tumours and >or=2 occurrences within 24 months and was conducted from June 2004 to March 2007. Median follow-up for patients without recurrence was 12 months. Patients were randomized to BCG or mononuclear cells collected by apheresis after ex vivo cell processing and activation (BEXIDEM). Either arm treatment consisted of 6 weekly instillations and 2 cycles of 3 weekly instillations at months 3 and 6. Toxicity profile (primary endpoint) and prophylactic effects (secondary endpoint) were assessed.

Results: Patient characteristics were evenly distributed. Of 73 treated with BCG and 64 with BEXIDEM, 85% vs. 45% experienced AEs and 26% vs. 14% serious AEs (SAE), respectively (p<0.001). Recurrence occurred significantly less frequent with BCG than with BEXIDEM (12% vs. 38%; p<0.001).

Discussion: This initial report of autologous intravesical macrophage cell therapy in BC demonstrates BEXIDEM treatment to be safe. Recurrence rates were significantly lower with BCG however. As the efficacy of BEXIDEM remains uncertain, further data, e.g. marker lesions studies, are warranted.

Trial Registration: The trial has been registered in the ISRCTN registry http://isrctn.org under the registration number ISRCTN35881130.