Treatment of inoperable or metastatic paragangliomas and pheochromocytomas with peptide receptor radionuclide therapy using 177Lu-DOTATATE

Abstract

Objectives Inoperable or metastatic paragangliomas (PGLs) and malignant pheochromocytomas (PCCs) are rare tumours with limited options for systemic treatment. Aim of this study was to assess the safety and efficacy of the radiolabelled somatostatin analogue (177LutetiumDOTA0-Tyr3)octreotate (177Lu-DOTATATE) for the treatment of PGLs and PCCs. Methods Patients with histologically proven inoperable or malignant PGLs and PCCs treated with 177Lu-DOTATATE at our centre were retrospectively analysed. Patients were treated with up to four cycles of 177Lu-DOTATATE with an intended dose of 7.4 Gb per cycle. Response was assessed with use of RECIST 1.1. Results Thirty patients were included: 17 with parasympathetic, 10 with sympathetic PGLs and 3 with PCCs. Grade 3/4 subacute haematotoxicity occurred in 6 (20%) of patients. A reversible subacute adverse event due to cardiac failure following possible catecholamine release occurred in two patients. Best tumour response was partial response in 7 (23%) and stable disease in 20 (67%), whereas 3 (10%) patients had progressive disease. In 20 patients with baseline disease progression, tumour control was observed in 17 (85%); the median progression-free survival was 91 months in patients with parasympathetic PGLs, 13 months in patients with sympathetic PGLs and 10 months in patients with metastatic PCCs. Conclusion This study suggests that PRRT with 177Lu-DOTATATE is a safe and effective treatment option for patients with inoperable or malignant PGL and PCC.

177Lu-DOTATATE therapy in metastatic/inoperable pheochromocytoma-paraganglioma

“…In the Netter-1 trial including 116 patients with mid-gut NET who received PRRT, grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1, 2, and 9%, respectively, whereas none of them developed nephrotoxicity and myelodysplastic syndrome (MDS) ( 21 ). Although catecholaminergic crisis and tumor lysis syndrome have been reported in PPGL patients receiving PRRT ( 22 , 23 ), none of our patients developed these adverse effects. However, most of our secretory PPGLs had received adequate alpha blockade before being subjected to therapy which might have masked the potential for catecholaminergic crisis.…”

‘Peptide receptor radionuclide therapy in the management of advanced pheochromocytoma and paraganglioma: A systematic review and meta‐analysis’

“…Though the experience with PRRT is predominantly limited to gastroenteropancreatic neuroendocrine tumours, few studies have also evaluated its efficacy and safety in PPGLs . However, the individual studies have been conducted with limited number of patients and the precise effect of PRRT in treatment of advanced PPGLs is currently unclear.…”

Strategies Towards Improving Clinical Outcomes of Peptide Receptor Radionuclide Therapy

“…In our study, 177 Lu-DOTATATE therapy in 27 PGL and 3 PCC patients, with 67% of them having progressive disease at baseline, resulted in PR and SD in 23% and 67% of the patients, respectively. Median PFS of the total study population was 30 months but was increased to 91 months in the subgroup of patients with parasympathetic PGL [13]. In another study involving 177 Lu-DOTATATE therapy in 13 PGL and 9 PCC patients, the PR and SD rates were 9% and 91%, respectively.…”