Thyroid and hepatic function after high‐dose <sup>131</sup>I‐metaiodobenzylguanidine (<sup>131</sup>I‐MIBG) therapy for neuroblastoma

Quach, Alekist; Ji, Lingyun; Mishra, Vikash Kumar; Sznewajs, Aimee; Veatch, Janet; Huberty, John P.; Franc, Benjamin L.; Sposto, Richard; Groshen, Susan; Wei, Dan; FitzGerald, Paul A.; Maris, John M.; Yanik, Gregory A.; Hawkins, Randall A.; Villablanca, Judith G.; Matthay, Katherine K.

doi:10.1002/pbc.22767

Cited by 58 publications

(40 citation statements)

References 28 publications

(26 reference statements)

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“…Historically, 2 late toxicities of MIBG, hypothyroidism and secondary leukemia, have been reported with therapeutic doses of carrier-added 131 I-MIBG. Hypothyroidism is a frequent late effect of MIBG therapy, because of thyroid uptake of dissociated radioactive iodide anions (18). Myelodysplasia or leukemia after carrier-added MIBG has been reported, with a cumulative incidence of 4% at 4 y after therapy (8,19).…”

Section: Discussionmentioning

confidence: 99%

“…The planned dose (note that dose level is used throughout to indicate activity) levels were 444, 555, 666, and 777 MBq/kg (12,15,18, and 21 mCi/kg, respectively) of NCA 131 I-MIBG, replicating the doses used in our prior phase I study of carrier-added MIBG (9). The dose was not escalated unless 0 of 3 or no more than 1 of 6 evaluable patients had DLT.…”

Section: Study Design and Statistical Methodsmentioning

confidence: 99%

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Dose Escalation Study of No-Carrier-Added ¹³¹I-Metaiodobenzylguanidine for Relapsed or Refractory Neuroblastoma: New Approaches to Neuroblastoma Therapy Consortium Trial

Matthay¹,

Weiss²,

Villablanca³

et al. 2012

J Nucl Med

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and 14 Molecular Insight Pharmaceuticals, Cambridge, Massachusetts 131 I-metaiodobenzylguanidine (MIBG) is specifically taken up in neuroblastoma, with a response rate of 20%-37% in relapsed disease. Nonradioactive carrier MIBG molecules inhibit uptake of 131 I-MIBG, theoretically resulting in less tumor radiation and increased risk of cardiovascular toxicity. Our aim was to establish the maximum tolerated dose of nocarrier-added (NCA) 131 I-MIBG, with secondary aims of assessing tumor and organ dosimetry and overall response. Methods: Eligible patients were 1-30 y old with resistant neuroblastoma, 131 I-MIBG uptake, and cryopreserved hematopoietic stem cells. A diagnostic dose of NCA 131 I-MIBG was followed by 3 dosimetry scans to assess radiation dose to critical organs and soft-tissue tumors. The treatment dose of NCA 131 I-MIBG (specific activity, 165 MBq/mg) was adjusted as necessary on the basis of critical organ tolerance limits. Autologous hematopoietic stem cells were infused 14 d after therapy to abrogate prolonged myelosuppression. Response and toxicity were evaluated on day 60. The NCA 131 I-MIBG was escalated from 444 to 777 MBq/kg (12-21 mCi/kg) using a 3 1 3 design. Dose-limiting toxicity (DLT) was failure to reconstitute neutrophils to greater than 500/mL within 28 d or platelets to greater than 20,000/mL within 56 d, or grade 3 or 4 nonhematologic toxicity by Common Terminology Criteria for Adverse Events (version 3.0) except for predefined exclusions. Results: Three patients each were evaluable at 444, 555, and 666 MBq/kg without DLT. The dose of 777 MBq/kg dose was not feasible because of organ dosimetry limits; however, 3 assigned patients were evaluable for a received dose of 666 MBq/kg, providing a total of 6 patients evaluable for toxicity at 666 MBq/kg without DLT. Mean whole-body radiation was 0.23 mGy/MBq, and mean organ doses were 0.92, 0.82, and 1.2 mGy/MBq of MIBG for the liver, lung, and kidney, respectively. Eight patients had 13 soft-tissue lesions with tumor-absorbed doses of 26-378 Gy. Four of 15 patients had a complete (n 5 1) or partial (n 5 3) response, 1 had a mixed response, 4 had stable disease, and 6 had progressive disease. Conclusion: NCA 131 I-MIBG with autologous peripheral blood stem cell transplantation is feasible at 666 MBq/kg without significant nonhematologic toxicity and with promising activity.

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Section: Discussionmentioning

confidence: 99%

Section: Study Design and Statistical Methodsmentioning

confidence: 99%

Dose Escalation Study of No-Carrier-Added ¹³¹I-Metaiodobenzylguanidine for Relapsed or Refractory Neuroblastoma: New Approaches to Neuroblastoma Therapy Consortium Trial

Matthay¹,

Weiss²,

Villablanca³

et al. 2012

J Nucl Med

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“…Tositumomab, an anti-CD20 MAb combined with 131 I, is approved for the treatment of non-Hodgkin lymphoma, whereas 131 I-metaiodobenzylguanidine is used in pheochromocytoma, neuroblastoma and carcinoid tumors. As the radioactive iodine concentrates in thyroid cells, hypothyroidism may occur in 9-64% of patients (within 6-24 months or later) (136)(137)(138)(139)(140)(141). However, this side effect is preventable by the administration of oral iodine (Lugol solution or saturated solution of potassium iodide, SSKI) or potassium perchlorate (KClO 4 ).…”

Section: Iodine-based Anticancer Radioimmunotherapymentioning

confidence: 99%

Thyroid Dysfunction as an Unintended Side Effect of Anticancer Drugs

Torino

Barnabei²,

Paragliola

et al. 2013

Thyroid

102

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“…MIBG therapy in particular has been linked to new-onset thyroid dysfunction, secondary leukemias, and myelodysplastic syndrome in early studies [173,174]. Pharmacogenomics is an evolving field that may assist in the understanding of genetic variations that may allow for prediction of risks for specific chemotherapy toxicities.…”

Section: Late Effectsmentioning

confidence: 99%

Overview and recent advances in the treatment of neuroblastoma

Whittle

Smith

Doherty

et al. 2017

Expert Review of Anticancer Therapy

311

258

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Introduction: Children with neuroblastoma have widely divergent outcomes, ranging from cure in >90% of patients with low risk disease to <50% for those with high risk disease. Recent research has shed light on the biology of neuroblastoma, allowing for more accurate risk stratification and treatment reduction in many cases, although newer treatment strategies for children with high-risk and relapsed neuroblastoma are needed to improve outcomes. Areas covered: Neuroblastoma epidemiology, diagnosis, risk stratification, and recent advances in treatment of both newly diagnosed and relapsed neuroblastoma. Expert commentary: The identification of newer tumor targets and of novel cell-mediated immunotherapy agents may lead to novel therapeutic approaches, and clinical trials for regimens designed to target individual genetic aberrations in tumors are underway. A combination of therapeutic modalities will likely be required to improve survival and cure rates for patients with high-risk neuroblastoma.ARTICLE HISTORY

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Thyroid and hepatic function after high‐dose ¹³¹I‐metaiodobenzylguanidine (¹³¹I‐MIBG) therapy for neuroblastoma

Cited by 58 publications

References 28 publications

Dose Escalation Study of No-Carrier-Added ¹³¹I-Metaiodobenzylguanidine for Relapsed or Refractory Neuroblastoma: New Approaches to Neuroblastoma Therapy Consortium Trial

Dose Escalation Study of No-Carrier-Added ¹³¹I-Metaiodobenzylguanidine for Relapsed or Refractory Neuroblastoma: New Approaches to Neuroblastoma Therapy Consortium Trial

Thyroid Dysfunction as an Unintended Side Effect of Anticancer Drugs

Overview and recent advances in the treatment of neuroblastoma

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Thyroid and hepatic function after high‐dose 131I‐metaiodobenzylguanidine (131I‐MIBG) therapy for neuroblastoma

Cited by 58 publications

References 28 publications

Dose Escalation Study of No-Carrier-Added 131I-Metaiodobenzylguanidine for Relapsed or Refractory Neuroblastoma: New Approaches to Neuroblastoma Therapy Consortium Trial

Dose Escalation Study of No-Carrier-Added 131I-Metaiodobenzylguanidine for Relapsed or Refractory Neuroblastoma: New Approaches to Neuroblastoma Therapy Consortium Trial

Thyroid Dysfunction as an Unintended Side Effect of Anticancer Drugs

Overview and recent advances in the treatment of neuroblastoma

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Product

Resources

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Thyroid and hepatic function after high‐dose ¹³¹I‐metaiodobenzylguanidine (¹³¹I‐MIBG) therapy for neuroblastoma

Dose Escalation Study of No-Carrier-Added ¹³¹I-Metaiodobenzylguanidine for Relapsed or Refractory Neuroblastoma: New Approaches to Neuroblastoma Therapy Consortium Trial

Dose Escalation Study of No-Carrier-Added ¹³¹I-Metaiodobenzylguanidine for Relapsed or Refractory Neuroblastoma: New Approaches to Neuroblastoma Therapy Consortium Trial