Phase I/II radioimmunotherapy trial with iodine-131-labeled monoclonal antibody G250 in metastatic renal cell carcinoma

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 ¹³¹I (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 ≥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 ≥3 thrombocytopenia; the MTD was determined to be 90 mCi/m^{2 131}I. 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 ≥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.