A phase I clinical trial for [(131)I]meta-iodobenzylguanidine therapy in patients with refractory pheochromocytoma and paraganglioma

Refractory pheochromocytoma and paraganglioma (PPGL) have a poor prognosis and the treatment strategy remains to be established. This multi-institutional phase I study was performed to determine the safety, dose-limiting toxicity (DLT), and efficacy of [(131)I]-meta-iodobenzylguanidine ((131)I-mIBG) therapy for refractory PPGLs. Twenty patients with refractory PPGL were enrolled in this study. We administered fixed doses of (131)I-mIBG to all patients, delivering a second and third course of (131)I-mIBG to eight and three patients, respectively. During the 20 weeks after (131)I-mIBG injection, the authors surveyed the adverse events in accordance with the Common Terminology Criteria for Adverse Events. All patients experienced adverse events and adverse reactions, but none experienced a grade 4 adverse event. Twelve weeks after (131)I-mIBG injection, examinations for the evaluation of therapeutic effects was performed in accordance with the Response Evaluation Criteria in Solid Tumours (RECIST). The best overall response rates (based on RECIST categories) were 10% (complete response), 65% (stable disease), 15% (progressive disease), and 10% (not all evaluated). The efficacy and safety of (131)I-mIBG therapy was shown in patients with refractory PPGL, and DLT was observed in neither single nor repeated (131)I-mIBG therapy, indicating a tolerability for (131)I-mIBG therapy.