Lack of efficacy of two consecutive treatments of radioimmunotherapy with 131I-cG250 in patients with metastasized clear cell renal cell carcinoma

Purpose A previous activity dose-escalation study using I-131-labeled chimeric monoclonal antibody cG250 in patients with progressive metastatic renal cell carcinoma (RCC) resulted in occasional therapeutic responses. The present study was designed to determine the safety and therapeutic efficacy of two sequential high-dose treatments with I-131-cG250. Patients and Methods Patients (n = 29) with progressive metastatic RCC received a low dose of I-131-cG250 for assessment of preferential targeting of metastatic lesions, followed by the first radioimmunotherapy (RIT) with 2220 MBq/m(2) I-131-cG250 (n = 27) 1 week later. If no grade 4 hematologic toxicity was observed, a second low-dose I-131-cG250 (n = 20) was given 3 months later. When blood clearance was not accelerated, a second RIT of I-131-cG250 was administered at an activity-dose of 1110 MBq/m(2) (n = 3) or 1665 MBq/m(2) (n = 16). Patients were monitored weekly for toxicity, and tumor size was evaluated by computed tomography once every 3 months intervals. Results The maximum-tolerated dose (MTD) of the second RIT was 1,665 MBq/m(2) because of dose-limiting hematological toxicity. Based on an intention-to-treat analysis, after two RIT treatments, the disease stabilized in five of 29 patients, whereas it remained progressive in 14 of 29 patients. Two patients received no RIT, and eight of 29 received only one I-131-cG250 RIT because of grade 4 hematologic toxicity, formation of human antichimeric antibodies, or disease progression. Conclusion In patients with progressive end-stage RCC, the MTD of the second treatment was 75% of the MTD of the first RIT. In the majority of patients, two cycles of I-131-cl could be safely administered without severe toxicity. No objective responses were observed, but occasionally two RIT doses resulted in stabilization of previously progressive disease.