title: Phase I/II radioimmunotherapy trial with iodine-131-labeled monoclonal antibody G250 in metastatic renal cell carcinoma.
abstract: This Phase I/II radioimmunotherapy study was carried out to determine the maximum tolerated dose (MTD) and therapeutic potential of 131I-G250. Thirty-three patients with measurable metastatic renal cell carcinoma were treated. Groups of at least three patients received escalating amounts of 1311I (30, 45, 60, 75, and 90 mCi/m2) labeled to 10 mg of mouse monoclonal antibody G250, administered as a single i.v. infusion. Fifteen patients were studied at the MTD of activity. No patient had received prior significant radiotherapy; one had received prior G250. Whole-body scintigrams and single-photon emission computed tomography images were obtained in all patients. There was targeting of radioactivity to all known tumor sites that were > or =2 cm. Reversible liver function test abnormalities were observed in the majority of patients (27 of 33 patients). There was no correlation between the amount of 131I administered or hepatic absorbed radiation dose (median, 0.073 Gy/mCi) and the extent or nature of hepatic toxicity. Two of the first six patients at 90 mCi/m2 had grade > or =3 thrombocytopenia; the MTD was determined to be 90 mCi/m2 131I. Hematological toxicity was correlated with whole-body absorbed radiation dose. All patients developed human antimouse antibodies within 4 weeks posttherapy; retreatment was, therefore, not possible. Seventeen of 33 evaluable patients had stable disease. There were no major responses. On the basis of external imaging, 131I-labeled mouse monoclonal antibody G250 showed excellent localization to all tumors that were > or =2 cm. Seventeen of 33 patients had stable disease, with tumor shrinkage observed in two patients. Antibody immunogenicity restricted therapy to a single infusion. Studies with a nonimmunogenic G250 antibody are warranted.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. divgic@mskcc.org
authors.forename: C R
authors.initials: CR
authors.lastname: Divgi
authors.forename: N H
authors.initials: NH
authors.lastname: Bander
authors.forename: A M
authors.initials: AM
authors.lastname: Scott
authors.forename: J A
authors.initials: JA
authors.lastname: O'Donoghue
authors.forename: G
authors.initials: G
authors.lastname: Sgouros
authors.forename: S
authors.initials: S
authors.lastname: Welt
authors.forename: R D
authors.initials: RD
authors.lastname: Finn
authors.forename: F
authors.initials: F
authors.lastname: Morrissey
authors.forename: P
authors.initials: P
authors.lastname: Capitelli
authors.forename: J M
authors.initials: JM
authors.lastname: Williams
authors.forename: D
authors.initials: D
authors.lastname: Deland
authors.forename: A
authors.initials: A
authors.lastname: Nakhre
authors.forename: E
authors.initials: E
authors.lastname: Oosterwijk
authors.forename: S
authors.initials: S
authors.lastname: Gulec
authors.forename: M C
authors.initials: MC
authors.lastname: Graham
authors.forename: S M
authors.initials: SM
authors.lastname: Larson
authors.forename: L J
authors.initials: LJ
authors.lastname: Old
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001772:Blood Cell Count / Q000528:radiation effects; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D008099:Liver / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy; D011874:Radiometry; D011877:Radionuclide Imaging; D014916:Whole-Body Irradiation
chemical_list: D000911:Antibodies, Monoclonal; C106533:G250 monoclonal antibody; D018796:Immunoconjugates; D007457:Iodine Radioisotopes