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

Journal of Translational Medicine

Research

Nicolas Thiounn¹  Marc Munsell²  Maximilian Burger³  Stefan Denzinger³  Marc O Grimm⁴  Manfred Wirth⁴  Fernando J Jimenz-Cruz⁵  Manuel S Chapado⁶  Joachim W Thüroff⁷  Imre Romics⁸  Jeff Sherman⁹  Bonnie Mills^1,10  Tung Koh^1,10  Laszlo Kisbenedek^1,11  Domján Zsolt^1,12  Zoltán Szabo^1,12  Gerard Benoit^1,13  Bertrand Tombal^1,14  Tamas Kiss^1,15  Jozsef Kondas^1,16 

[1]Dept. d'Urologie, Hopital Necker - Pôle Adulte, Paris, France

[2]Dept. of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, USA

[3]Dept. of Urology, Caritas St. Josef Medical Centre, University of Regensburg, Regensburg, Germany

[4]Dept. of Urology, Carl-Gustav Carus University, Dresden, Germany

[5]Dept. of Urology, Hospital La Fe, Valencia, Spain

[6]Dept. of Urology, Hospital Universitario Principe de Asturias, Madrid, Spain

[7]Dept. of Urology, Johannes Gutenberg University, Mainz, Germany

[8]Dept. of Urology, Semmelweis Egyetem Urológiai Klinika, Budapest, Hungary

[9]HorizonTherapeutics, Northbrook, IL, USA

[10]Inspiration Biopharmaceuticals, Laguna Niguel, CA, USA

[11]Kórház Urológiai Osztály, Fövárosi Önkormányzat Jahn Ferenc Dél-Pesti, Budapest, Hungary

[12]Kórháza Urológiai Osztály, Bács-Kiskun Megyei Önkormányzat, Kecskemét, Hungary

[13]Service Urologie, CHU Kremlin-Bicetre, Kremlin-Bicetre, France

[14]Urology Unit, Clinique Unversitaire Saint Luc (UCL), Brussels, Belgium

[15]Urológiai Osztály, Fővárosi Önkormányzat Bajcsy-Zsilinszky Kórháza, Budapest, Hungary

[16]Urológiai Sebészeti Osztály, Fővárosi Önkormányzat Péterfy Sándor utcai, Budapest, Hungary

关键词: Bladder Cancer;    Human Serum Albumin;    Prostatitis;    Neopterin;    Intravesical Instillation;   

DOI  :  10.1186/1479-5876-8-54

 received in 2010-03-16, accepted in 2010-06-08,  发布年份 2010

来源: Springer

【 摘 要 】

IntroductionWhile 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 methodsThis 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.ResultsPatient 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).DiscussionThis 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 registrationThe trial has been registered in the ISRCTN registry http://isrctn.org under the registration number ISRCTN35881130.

【 授权许可】

CC BY   
© Burger et al; licensee BioMed Central Ltd. 2010