lutetium-lu-177-dotatate and Pheochromocytoma

Topics: 3-Iodobenzylguanidine; Humans; Iodine Radioisotopes; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pheochromocytoma; Precision Medicine; Radiopharmaceuticals

Inoperable and metastatic pheochromocytomas and paragangliomas (PPGLs) present a therapeutic challenge with current treatment options being limited to radiolabelled meta-iodo-benzyl-guanidine (MIBG) and systemic chemotherapy. Peptide receptor radionuclide therapy (PRRT) seems to be a promising option for these patients with few studies reporting favourable response. This systematic review was conducted to evaluate the efficacy and safety of PRRT in patients with advanced PPGLs.. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches in PubMed, Scopus and Embase were made using relevant keywords and articles up to May 2019 were included. Data on efficacy and toxicity were extracted from the individual articles, and pooled estimates were generated using meta-analysis.. Peptide receptor radionuclide therapy is a safe and efficacious treatment option for advanced PPGLs and may be considered a viable alternative to chemotherapy and I-

Topics: Female; Heterocyclic Compounds; Humans; Male; Octreotide; Organometallic Compounds; Paraganglioma; Peptides, Cyclic; Pheochromocytoma; Radiopharmaceuticals; Receptors, Peptide

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.. 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.. 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.. This study suggests that PRRT with 177Lu-DOTATATE is a safe and effective treatment option for patients with inoperable or malignant PGL and PCC.

Topics: Adrenal Gland Neoplasms; Adult; Aged; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Octreotide; Organometallic Compounds; Paraganglioma; Pheochromocytoma; Radiation Dosage; Radioisotopes; Receptors, Peptide; Retrospective Studies; Treatment Outcome

Treatment options for unresectable paraganglioma (PGL)/pheochromocytoma (PCC), especially with uncontrolled secondary hypertension (HTN), are limited. Preliminary studies with peptide receptor radionuclide therapy (PRRT) suggest efficacy, but data on HTN control and survival are lacking. We assessed PRRT outcomes in such patients from two referral centers.. Twenty consecutive patients (13 men; age range, 21 to 77 years) with high somatostatin receptor (SSTR) expression treated with 177Lu-DOTA-octreotate, nine with radiosensitizing chemotherapy, were retrospectively reviewed. Median cumulative activity was 22 GBq (median 4 cycles). Fourteen patients were treated for uncontrolled HTN and six for progressive or symptomatic metastatic disease or local recurrence.. Three months after PRRT, 8 of 14 patients treated for HTN required reduced medication doses, 5 had no change in anti-HTN doses, and 1 was lost to follow-up. Eighty-six percent had serum chromogranin-A reduction. Of the entire cohort, 36% had disease regression (29% partial and 7% minor response) on computed tomography, with stable findings in 50%. Three other patients had bony disease evaluable only on SSTR imaging (2 partial response and 1 stable). Median progression-free survival was 39 months; median overall survival was not reached (5 deaths; median follow-up, 28 months). Four patients had grade 3 lymphopenia; 2 had grade 3 thrombocytopenia. Renal impairment in 2 patients was attributed to underlying disease processes.. PRRT achieves worthwhile clinical and biochemical responses with low toxicity and encouraging survival in PGL/PCC. Because PRRT has logistic and radiation-safety advantages compared to 131I-MIBG therapy, further prospective evaluation is warranted.

Topics: Adrenal Gland Neoplasms; Adult; Aged; Biopsy, Needle; Cohort Studies; Coordination Complexes; Disease-Free Survival; Dose-Response Relationship, Radiation; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Male; Middle Aged; Octreotide; Paraganglioma; Pheochromocytoma; Prognosis; Radioisotopes; Receptors, Peptide; Retrospective Studies; Risk Assessment; Survival Analysis; Treatment Outcome; Young Adult

Radionuclide therapy has been used to treat patients with progressive/metastatic paragangliomas (PGLs) and phaeochromocytomas (PCCs). The aim of the present study is to retrospectively compare the therapeutic outcomes of these modalities in patients with progressive/metastatic PCCs and PGLs.. Patients with progressive/metastatic PGLs and PCCs that were subjected to radionuclide treatment in our department were retrieved from our department's database for the period 1998-2013. Overall survival (OS), progression free survival (PFS), event free survival (EFS), and response to treatment were calculated. Treatment toxicity was documented.. Twenty-two patients with progressive/metastatic PGLs or PCCs were treated with either (131)I-MIBG, (90)Y-DOTATATE or (177)Lu-DOTATATE. A total of 30 treatments were administered (16 treatments with (131)I-MIBG, 2 with (177)Lu-DOTATATE, and 12 with (90)Y-DOTATATE. Patients treated with PRRT had increased PFS and response to treatment compared to (131)I-MIBG treated patients (P < 0.05). However, difference in OS was non significant (P = 0.09). There was no difference in major toxicities between groups. When comparing only patients with PGLs, OS, PFS, EFS, and response to treatment were significantly higher in the PRRT treatment group.. PRRT treatment offers increased OS, PFS, EFS, and response to treatment compared to (131)I-MIBG therapy in patients with progressive/malignant PGLs.

Topics: 3-Iodobenzylguanidine; Acute Kidney Injury; Adrenal Gland Neoplasms; Adult; Aged; Chemotherapy, Adjuvant; Female; Humans; Male; Middle Aged; Octreotide; Organometallic Compounds; Paraganglioma; Pheochromocytoma; Radiopharmaceuticals; Retrospective Studies; Yttrium Radioisotopes