Abstract
ObjectiveIn this phase II study, we aimed to investigate the efficacy and safety of single-dose [131I]meta-iodobenzylguanidine (131I-mIBG) therapy in patients with refractory pheochromocytoma and paraganglioma (PPGL).Patients and methodsThis study was designed as an open-label, single-arm, multi-center, phase II clinical trial. The enrolled patients were administered 7.4 GBq of 131I-mIBG. Its efficacy was evaluated 12 and 24 weeks later, and its safety was monitored continuously until the end of the study. We evaluated the biochemical response rate as the primary endpoint using the one-sided exact binomial test based on the null hypothesis (≤ 5%).ResultsSeventeen patients were enrolled in this study, of which 16 were treated. The biochemical response rate (≥ 50% decrease in urinary catecholamines) was 23.5% (90% confidence interval: 8.5–46.1%, p = 0.009). The radiographic response rates, determined with CT/MRI according to the response evaluation criteria in solid tumors (RECIST) version 1.1 and 123I-mIBG scintigraphy were 5.9% (0.3%–25.0%) and 29.4% (12.4%–52.2%), respectively. The most frequent non-hematologic treatment-emergent adverse events (TEAEs) were gastrointestinal symptoms including nausea, appetite loss, and constipation, which were, together, observed in 15 of 16 patients. Hematologic TEAEs up to grade 3 were observed in 14 of 16 patients. No grade 4 or higher TEAEs were observed. All patients had experienced at least one TEAE, but no fatal or irreversible TEAEs were observed.ConclusionA single dose 131I-mIBG therapy was well tolerated by patients with PPGL, and statistically significantly reduced catecholamine levels compared to the threshold response rate, which may lead to an improved prognosis for these patients.
Highlights
Pheochromocytomas and paragangliomas (PPGLs) are rare tumors, genealogically derived from the neural crest cells that develop into the sympathetic and parasympathetic nervous systems
Secondary endpoints were defined as the objective response rate (ORR) upon CT or MRI according to the response evaluation criteria in solid tumors (RECIST) version 1.1; the scintigraphic response upon 123I-mIBG scintigraphy; patients’ quality of life (QOL) according to the European Organization for Research and Treatment of Cancer (EORTC) QLQC30, EuroQol 5 Dimensions (EQ-5D-5L) questionnaire; and patients’ safety [14, 15]
Follow-up was discontinued in two patients (13%) because of disease progression at the 12-week follow-up and in one patient (6%) because of a serious adverse event at 20 weeks after 131I-mIBG therapy
Summary
Pheochromocytomas and paragangliomas (PPGLs) are rare tumors, genealogically derived from the neural crest cells that develop into the sympathetic and parasympathetic nervous systems. [131I]meta-iodobenzylguanidine (131I-mIBG) is a radioactive agent with high-energy beta-ray emission, first developed by Wieland et al in 1980 [7] It is taken up through neuronal uptake-1 transporter into tumor cells derived from the abovementioned neural crest cells, such as pheochromocytomas, medullary thyroid cancer, and. There have been only few prospective studies due to the extremely low incidence of PPGL [12] Based on those background, in December 2012, the Advanced Medical Care Committee, sponsored by the Japanese Ministry of Health, Labour and Welfare, promoted 131I-mIBG to the status of an anticancer drug with high priority for clinical development. This study was designed and data provided by FUJIFILM Toyama Chemical Co., Ltd
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