Phase I radioimmunotherapy of metastatic renal cell carcinoma with I-131-labeled chimeric monoclonal antibody G250

Clinical tumor targeting studies with chimeric monoclonal antibody G250 (cG 250) 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 I-131-labeled cG250 in pati ents with progressive metastatic RCC, All patients (n = 12) received a diag nostic i.v. infusion of 5 mg of cG250 labeled with 222 MBq of I-131. If acc umulation of the antibody in metastatic lesions was observed, patients were hospitalized and a second, therapeutic, i.v. infusion of 5 mg of cG250 lab eled with a high dose of I-131 was administered (n = 8). Three patients per dose level were entered, starting at 1665 MBq/m(2.) If no dose-limiting to xicity occurred, the study continued at the next dose level (555 MBq/m(2) i ncrease). 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/m(2), grade IV hematological toxicity was obse rved, which was defined as dose limiting. Thus, the MTD was set at 2220 MBq /m(2). In one patient (2220 MBq/m2), stable disease (lasting 3-6 months) wa s achieved, whereas another patient (2220 MBq/m(2)) showed a partial respon se 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 warra nt further study in a phase II setting at the MTD to determine the efficacy of radioimmunotherapy for metastatic RCC.