Radioimmunotherapy with [131I]cG250 in Patients with Metastasized Renal Cell Cancer: Dosimetric Analysis and Immunologic Response

• Published in: Clinical cancer research 2005-10, Vol.11 (19), p.7178s-7186s
• Main Authors: BROUWERS, Adrienne H, BUIJS, Wilhelmina C. A. M, MULDERS, Peter F. A, DE MULDER, Pieter H. M, VAN DEN BROEK, Wim J. M, MALA, Carola, OOSTERWIJK, Egbert, BOERMAN, Otto C, CORSTENS, Frans H. M, OYEN, Wim J. G
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - pharmacology; Antineoplastic agents; Biological and medical sciences; carbonic anhydrase isotype IX; Carcinoma, Renal Cell - therapy; clinical; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Disease Progression; Dose-Response Relationship, Radiation; dosimetry; Female; Humans; Iodine Radioisotopes - therapeutic use; Kidney Neoplasms - therapy; Kidneys; Kinetics; Male; Medical sciences; Middle Aged; Neoplasm Metastasis; Nephrology. Urinary tract diseases; pharmacokinetic; Pharmacology. Drug treatments; Radioimmunotherapy - methods; Radiometry; Recombinant Fusion Proteins - chemistry; renal cell carcinoma; Tumors of the urinary system
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-1004-0010

Purpose: A study was designed to define the therapeutic efficacy, safety, and toxicity of two sequential high-dose treatments of radioimmunotherapy with [ 131 I]cG250 in patients with metastasized renal cell carcinoma. Here, we report the dosimetric analysis and the relationship between the development of a human antichimeric antibody response and altered pharmacokinetics. Experimental Design: Patients ( n = 29) with progressive metastatic renal cell carcinoma received a low dose (222 MBq) of [ 131 I]cG250 for dosimetric analysis, followed by the first radioimmunotherapy with 2,220 MBq/m 2 [ 131 I]cG250 ( n = 27) 1 week later. If no grade 4 hematologic toxicity was observed, a second low dose of [ 131 I]cG250 ( n = 20) was given 3 months later. Provided that no accelerated blood clearance was observed, a second radioimmunotherapy of [ 131 I]cG250 was administered at an activity-dose level of 1,110 MBq/m 2 ( n = 3) or 1,665 MBq/m 2 ( n = 16). After each administration, whole-body images were obtained and the pharmacokinetics and the development of human antichimeric antibody responses were determined. Radiation-absorbed doses were calculated for whole body, red marrow, organs, and metastases. Results: No correlation was found between hematologic toxicity and radiation-absorbed dose to the whole body or bone marrow, nor administered activity (MBq and MBq/kg). The tumor-absorbed doses varied largely. An inverse relation between tumor size and radiation-absorbed dose was found. Most tumor lesions received