Efficacy and Safety of High-Specific-Activity 131I-MIBG Therapy in Patients with Advanced Pheochromocytoma or Paraganglioma

J Nucl Med. 2019 May;60(5):623-630. doi: 10.2967/jnumed.118.217463. Epub 2018 Oct 5.

Abstract

Patients with metastatic or unresectable (advanced) pheochromocytoma and paraganglioma (PPGL) have poor prognoses and few treatment options. This multicenter, phase 2 trial evaluated the efficacy and safety of high-specific-activity 131I-meta-iodobenzylguanidine (HSA 131I-MIBG) in patients with advanced PPGL. Methods: In this open-label, single-arm study, 81 PPGL patients were screened for enrollment, and 74 received a treatment-planning dose of HSA 131I-MIBG. Of these patients, 68 received at least 1 therapeutic dose (∼18.5 GBq) of HSA 131I-MIBG intravenously. The primary endpoint was the proportion of patients with at least a 50% reduction in baseline antihypertensive medication use lasting at least 6 mo. Secondary endpoints included objective tumor response as assessed by Response Evaluation Criteria in Solid Tumors version 1.0, biochemical tumor marker response, overall survival, and safety. Results: Of the 68 patients who received at least 1 therapeutic dose of HSA 131I-MIBG, 17 (25%; 95% confidence interval, 16%-37%) had a durable reduction in baseline antihypertensive medication use. Among 64 patients with evaluable disease, 59 (92%) had a partial response or stable disease as the best objective response within 12 mo. Decreases in elevated (≥1.5 times the upper limit of normal at baseline) serum chromogranin levels were observed, with confirmed complete and partial responses 12 mo after treatment in 19 of 28 patients (68%). The median overall survival was 36.7 mo (95% confidence interval, 29.9-49.1 mo). The most common treatment-emergent adverse events were nausea, myelosuppression, and fatigue. No patients had drug-related acute hypertensive events during or after the administration of HSA 131I-MIBG. Conclusion: HSA 131I-MIBG offers multiple benefits, including sustained blood pressure control and tumor response in PPGL patients.

Keywords: high-specific-activity 131I-MIBG; neuroendocrine tumors; paraganglioma; pheochromocytoma; rare; ultra-orphan disease.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Iodobenzylguanidine / adverse effects*
  • 3-Iodobenzylguanidine / therapeutic use*
  • Adolescent
  • Adrenal Gland Neoplasms / metabolism
  • Adrenal Gland Neoplasms / pathology
  • Adrenal Gland Neoplasms / radiotherapy*
  • Biomarkers, Tumor / metabolism
  • Female
  • Humans
  • Male
  • Paraganglioma / metabolism
  • Paraganglioma / pathology
  • Paraganglioma / radiotherapy*
  • Pheochromocytoma / metabolism
  • Pheochromocytoma / pathology
  • Pheochromocytoma / radiotherapy*
  • Safety*
  • Survival Analysis
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • 3-Iodobenzylguanidine