title: Phase I radioimmunotherapy of metastatic renal cell carcinoma with 131I-labeled chimeric monoclonal antibody G250.
abstract: Clinical tumor targeting studies with chimeric monoclonal antibody G250 (cG250) in renal cell carcinoma (RCC) patients indicated the potential use of this antibody for radioimmunotherapy. Here we report on a phase I activity dose escalation study to determine the safety, the maximum tolerable dose (MTD), and the possible therapeutic potential of 131I-labeled cG250 in patients with progressive metastatic RCC. All patients (n = 12) received a diagnostic i.v. infusion of 5 mg of cG250 labeled with 222 MBq of 131I. If accumulation of the antibody in metastatic lesions was observed, patients were hospitalized and a second, therapeutic, i.v. infusion of 5 mg of cG250 labeled with a high dose of 131I was administered (n = 8). Three patients per dose level were entered, starting at 1665 MBq/m2. If no dose-limiting toxicity occurred, the study continued at the next dose level (555 MBq/m2 increase). Most patients experienced mild nausea without vomiting. No other complaints were reported during hospitalization. In two of two patients who received a dose of 2775 MBq/m2, grade IV hematological toxicity was observed, which was defined as dose limiting. Thus, the MTD was set at 2220 MBq/m2. In one patient (2220 MBq/m2), stable disease (lasting 3-6 months) was achieved, whereas another patient (2220 MBq/m2) showed a partial response that is ongoing (>9 months). The minor responses observed in this phase I trial in patients with an advanced stage of RCC are encouraging and warrant further study in a phase II setting at the MTD to determine the efficacy of radioimmunotherapy for metastatic RCC.
authors.affiliation: Department of Urology, University Hospital Nijmegen, The Netherlands.
authors.forename: M G
authors.initials: MG
authors.lastname: Steffens
authors.forename: O C
authors.initials: OC
authors.lastname: Boerman
authors.forename: P H
authors.initials: PH
authors.lastname: de Mulder
authors.forename: W J
authors.initials: WJ
authors.lastname: Oyen
authors.forename: W C
authors.initials: WC
authors.lastname: Buijs
authors.forename: J A
authors.initials: JA
authors.lastname: Witjes
authors.forename: W J
authors.initials: WJ
authors.lastname: van den Broek
authors.forename: J C
authors.initials: JC
authors.lastname: Oosterwijk-Wakka
authors.forename: F M
authors.initials: FM
authors.lastname: Debruyne
authors.forename: F H
authors.initials: FH
authors.lastname: Corstens
authors.forename: E
authors.initials: E
authors.lastname: Oosterwijk
mesh_terms: D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016499:Radioimmunotherapy / Q000009:adverse effects; D011877:Radionuclide Imaging; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D011993:Recombinant Fusion Proteins