Radioimmunotherapy with [131I]cG250 in patients with metastasized renal cell cancer: dosimetric analysis and immunologic response
| Autor: | Peter F.A. Mulders, C. Mala, Egbert Oosterwijk, W.C.A.M. Buijs, Frans H.M. Corstens, Otto C. Boerman, Adrienne H. Brouwers, Wim J.G. Oyen, Wim J.M. van den Broek, Pieter H.M. De Mulder |
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| Přispěvatelé: | University of Groningen, Guided Treatment in Optimal Selected Cancer Patients (GUTS) |
| Rok vydání: | 2005 |
| Předmět: |
Male
Cancer Research Pathology medicine.medical_treatment Aetiology screening and detection [ONCOL 5] COLORECTAL-CANCER Iodine Radioisotopes Monoclonal antibody G250 Renal cell carcinoma Immune Regulation [NCMLS 2] Neoplasm Metastasis Antibodies Monoclonal Middle Aged Kidney Neoplasms Pathogenesis and modulation of inflammation [N4i 1] medicine.anatomical_structure I-131 TOSITUMOMAB Oncology Radioimmunotherapy Toxicity Disease Progression Female NORMAL KIDNEY ANTIGEN G250 PHASE-II TRIAL medicine.drug Adult medicine.medical_specialty Recombinant Fusion Proteins TOSITUMOMAB THERAPY Pharmacokinetics CARBONIC-ANHYDRASE Translational research [ONCOL 3] medicine Humans NON-HODGKINS-LYMPHOMA Radiometry Carcinoma Renal Cell MONOCLONAL-ANTIBODY G250 Aged business.industry Girentuximab HEMATOLOGIC TOXICITY Dose-Response Relationship Radiation Immunotherapy gene therapy and transplantation [UMCN 1.4] medicine.disease Kinetics Bone marrow Functional Imaging [UMCN 1.1] Nuclear medicine business Kidney cancer |
| Zdroj: | Clinical Cancer Research, 11, 19 Pt 2, pp. 7178s-7186s Clinical Cancer Research, 11, 7178s-7186s Clinical Cancer Research, 11(19), 7178S-7186S. AMER ASSOC CANCER RESEARCH |
| ISSN: | 1078-0432 |
| Popis: | Purpose: A study was designed to define the therapeutic efficacy, safety, and toxicity of two sequential high-dose treatments of radioimmunotherapy with [131I]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 [131I]cG250 for dosimetric analysis, followed by the first radioimmunotherapy with 2,220 MBq/m2 [131I]cG250 (n = 27) 1 week later. If no grade 4 hematologic toxicity was observed, a second low dose of [131I]cG250 (n = 20) was given 3 months later. Provided that no accelerated blood clearance was observed, a second radioimmunotherapy of [131I]cG250 was administered at an activity-dose level of 1,110 MBq/m2 (n = 3) or 1,665 MBq/m2 (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 50 Gy. A relatively high number of patients developed a human antichimeric antibody response (8 of 27) with altered pharmacokinetics, hampering additional radioimmunotherapies in four of these patients. Conclusions: Dosimetric analysis did not adequately predict the degree of bone marrow toxicity. When human antichimeric antibody developed, the rapid clearance of radioactivity from the blood and body prohibited further treatment. According to the calculated absorbed dose in metastatic lesions, future radioimmunotherapy studies with radiolabeled cG250 should aim at treatment of small-volume disease or treatment in an adjuvant setting. |
| Databáze: | OpenAIRE |
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