This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brouwers, A. H. Articles by Oyen, W. J.G. Search for Related Content PubMed PubMed Citation Articles by Brouwers, A. H. Articles by Oyen, W. J.G. Social Bookmarking                            What's this?

Lack of Efficacy of Two Consecutive Treatments of Radioimmunotherapy With ¹³¹I-cG250 in Patients With Metastasized Clear Cell Renal Cell Carcinoma

From the Departments of Nuclear Medicine, Urology and Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Wilex AG, München, Germany; and the Department of Radiology, Rijnstate Hospital, Arnhem, The Netherlands

Address reprint requests to Adrienne H. Brouwers, MD, PhD, University Medical Center Groningen, University of Groningen, Department of Nuclear Medicine and Molecular Imaging, P.O. Box 30001, 9700 RB Groningen, the Netherlands; e-mail: a.h.brouwers{at}nucl.umcg.nl

PURPOSE: A previous activity dose-escalation study using ¹³¹I-labeled chimeric monoclonal antibody cG250 in patients with progressive metastatic renal cell carcinoma (RCC) resulted in occasional therapeutic responses. The present study was designed to determine the safety and therapeutic efficacy of two sequential high-dose treatments with ¹³¹I-cG250.

PATIENTS AND METHODS: Patients (n = 29) with progressive metastatic RCC received a low dose of ¹³¹I-cG250 for assessment of preferential targeting of metastatic lesions, followed by the first radioimmunotherapy (RIT) with 2220 MBq/m^{2 131}I-cG250 (n = 27) 1 week later. If no grade 4 hematologic toxicity was observed, a second low-dose ¹³¹I-cG250 (n = 20) was given 3 months later. When blood clearance was not accelerated, a second RIT of ¹³¹I-cG250 was administered at an activity-dose of 1110 MBq/m² (n = 3) or 1665 MBq/m² (n = 16). Patients were monitored weekly for toxicity, and tumor size was evaluated by computed tomography once every 3 months intervals.

RESULTS: The maximum-tolerated dose (MTD) of the second RIT was 1,665 MBq/m² because of dose-limiting hematological toxicity. Based on an intention-to-treat analysis, after two RIT treatments, the disease stabilized in five of 29 patients, whereas it remained progressive in 14 of 29 patients. Two patients received no RIT, and eight of 29 received only one ¹³¹I-cG250 RIT because of grade 4 hematologic toxicity, formation of human antichimeric antibodies, or disease progression.

CONCLUSION: In patients with progressive end-stage RCC, the MTD of the second treatment was 75% of the MTD of the first RIT. In the majority of patients, two cycles of ¹³¹I-cG250 could be safely administered without severe toxicity. No objective responses were observed, but occasionally two RIT doses resulted in stabilization of previously progressive disease.

Supported by Dutch Cancer Society grant No. KUN 99-1973, the Ludwig Institute for Cancer Research, New York, NY, and Wilex AG, München, Germany. E.O. was supported financially by the Ludwig Institute for Cancer Research, New York, NY.

Presented in part at the Society of Nuclear Medicine 2003 meeting in New Orleans, LA, the European Association of Nuclear Medicine 2003 meeting in Amsterdam, The Netherlands and the 10th Conference on Cancer Therapy with Antibodies & Immunoconjugates, Princeton, NJ, October 2004.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				A. H. Brouwers, P. F.A. Mulders, and W. J.G. Oyen Carbonic Anhydrase IX Expression in Clear Cell Renal Cell Carcinoma and Normal Tissues: Experiences From (Radio) Immunotherapy J. Clin. Oncol., August 1, 2008; 26(22): 3808 - 3809. [Full Text] [PDF]

				B. C. Leibovich, Y. Sheinin, C. M. Lohse, R. H. Thompson, J. C. Cheville, J. Zavada, and E. D. Kwon In Reply J. Clin. Oncol., August 1, 2008; 26(22): 3811 - 3812. [Full Text] [PDF]

				W. J. G. Oyen, L. Bodei, F. Giammarile, H. R. Maecke, J. Tennvall, M. Luster, and B. Brans Targeted therapy in nuclear medicine current status and future prospects Ann. Onc., November 1, 2007; 18(11): 1782 - 1792. [Abstract] [Full Text] [PDF]

				C. H.J. Lamers, S. Sleijfer, A. G. Vulto, W. H.J. Kruit, M. Kliffen, R. Debets, J. W. Gratama, G. Stoter, and E. Oosterwijk Treatment of Metastatic Renal Cell Carcinoma With Autologous T-Lymphocytes Genetically Retargeted Against Carbonic Anhydrase IX: First Clinical Experience J. Clin. Oncol., May 1, 2006; 24(13): e20 - e22. [Full Text] [PDF]