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Open Access Research

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

Maximilian Burger1*, Nicolas Thiounn2, Stefan Denzinger1, Jozsef Kondas3, Gerard Benoit4, Manuel S Chapado5, Fernando J Jimenz-Cruz6, Laszlo Kisbenedek7, Zoltán Szabo8, Domján Zsolt8, Marc O Grimm9, Imre Romics10, Joachim W Thüroff11, Tamas Kiss12, Bertrand Tombal13, Manfred Wirth9, Marc Munsell14, Bonnie Mills15, Tung Koh15 and Jeff Sherman16

Author Affiliations

1 Dept. of Urology, Caritas St. Josef Medical Centre, University of Regensburg, Regensburg, Germany

2 Dept. d'Urologie, Hopital Necker - Pôle Adulte, Paris, France

3 Urológiai Sebészeti Osztály, Fővárosi Önkormányzat Péterfy Sándor utcai, Budapest, Hungary

4 Service Urologie, CHU Kremlin-Bicetre, Kremlin-Bicetre, France

5 Dept. of Urology, Hospital Universitario Principe de Asturias, Madrid, Spain

6 Dept. of Urology, Hospital La Fe, Valencia, Spain

7 Kórház Urológiai Osztály, Fövárosi Önkormányzat Jahn Ferenc Dél-Pesti, Budapest, Hungary

8 Kórháza Urológiai Osztály, Bács-Kiskun Megyei Önkormányzat, Kecskemét, Hungary

9 Dept. of Urology, Carl-Gustav Carus University, Dresden, Germany

10 Dept. of Urology, Semmelweis Egyetem Urológiai Klinika, Budapest, Hungary

11 Dept. of Urology, Johannes Gutenberg University, Mainz, Germany

12 Urológiai Osztály, Fővárosi Önkormányzat Bajcsy-Zsilinszky Kórháza, Budapest, Hungary

13 Urology Unit, Clinique Unversitaire Saint Luc (UCL), Brussels, Belgium

14 Dept. of Biostatistics, The University of Texas M. D. Anderson Cancer Center Houston, USA

15 Inspiration Biopharmaceuticals, Laguna Niguel, CA, USA

16 HorizonTherapeutics, Northbrook, IL, USA

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Journal of Translational Medicine 2010, 8:54  doi:10.1186/1479-5876-8-54

Published: 8 June 2010

Abstract

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 ≥ 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 webcite under the registration number ISRCTN35881130.