Is there a benefit of 131I-MIBG therapy in the treatment of children with stage 4 neuroblastoma?

Schmidt, Matthias; Simon, Thorsten; Hero, Barbara; Eschner, W.; Dietlein, Markus; Sudbrock, F.; Bongartz, Rudolf; Berthold, Frank; Schicha, H.

doi:10.1055/s-0038-1625111

Cited by 41 publications

(3 citation statements)

References 25 publications

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“…Forty-one patients at an Amsterdam center treated with two cycles of 131 I-MIBG prior to addition of chemotherapy had a response rate to the MIBG of 66% (43). German studies evaluated the addition of MIBG therapy at the end of induction and prior to myeloablative therapy for patients with residual MIBG positive disease, with a response rate of 46%, but no improvement in overall survival (44). A Children's Oncology Group pilot trial (ANBL09P1) will test the addition of MIBG with vincristine and irinotecan prior to myeloablative therapy for all high-risk patients, regardless of residual disease, and if feasibility and tolerability is demonstrated, a randomized trial will be undertaken.…”

Section: Targeting the Human Norepinephrine Transporter (Hnet) With Mibgmentioning

confidence: 99%

Promising Therapeutic Targets in Neuroblastoma

Matthay

George²,

Yu³

2012

Clinical Cancer Research

173

144

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Neuroblastoma, the most common extra- cranial solid tumor in children, is derived from neural crest cells. Nearly half of patients present with metastatic disease, and have 5-year EFS of less than 50%. New approaches with targeted therapy may improve efficacy without increased toxicity. The current review will evaluate three promising targeted therapies, including 131I-metaiodobenzylguanidine (MIBG), a radiopharmaceutical taken up by the human norepinephrine transporter expressed in 90% of neuroblastomas, immunotherapy with monoclonal antibodies targeting the GD2 ganglioside, expressed on 98% of neuroblastoma cells, and inhibitors of ALK, a tyrosine kinase which is mutated or amplified in approximately 10% of neuroblastoma and expressed on the surface of most neuroblastoma cells. Early phase trials have confirmed the activity of 131I-MIBG in relapsed neuroblastoma, with response rates of about 30%, but the technical aspects of administration of large amounts of radioactivity in young children and the limited access have hindered incorporation into treatment of newly diagnosed patients. Anti-GD2 antibodies have also demonstrated activity in relapsed disease, and a recent phase III randomized trial showed a significant improvement in event-free survival for patients receiving chimeric anti-GD2 (ch14.18) combined with cytokines and isotretinoin after myeloablative consolidation therapy. A recently approved small molecule inhibitor of ALK has promising pre-clinical activity for neuroblastoma, and is currently in phase I and II trials. This is the first agent directed to a specific mutation in neuroblastoma, and marks a new step toward personalized therapy for neuroblastoma. Further clinical development of targeted treatments offers new hope for children with neuroblastoma.

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Section: Targeting the Human Norepinephrine Transporter (Hnet) With Mibgmentioning

confidence: 99%

Promising Therapeutic Targets in Neuroblastoma

Matthay

George²,

Yu³

2012

Clinical Cancer Research

173

144

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“…Schmidt and colleagues retrospectively analyzed data from a German neuroblastoma trial in which 40 of 111 patients with residual disease following induction therapy were treated with 131 I-MIBG [13]. Although significantly improved 3-year event-free survival and overall survival was observed in the cohort treated with 131 I-MIBG, no difference in outcome was seen in a subgroup analysis of 66 patients who underwent high-dose chemotherapy with autologous stem cell transplantation.…”

Section: 131i-meta-iodobenzylguanidine (Mibg)mentioning

confidence: 99%

Emerging and investigational therapies for neuroblastoma

Applebaum

Desai

Bender

et al. 2017

Expert Opinion on Orphan Drugs

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Introduction Treatment for children with clinically aggressive, high-risk neuroblastoma remains challenging. Less than 50% of patients with high-risk neuroblastoma will survive long-term with current therapies, and survivors are at risk for serious treatment-related late toxicities. Here, we review new and evolving treatments that may ultimately improve outcome for children with high-risk neuroblastoma with decreased potential for late adverse events. Areas covered New strategies for treating high-risk neuroblastoma are reviewed including: radiotherapy, targeted cytotoxics, biologics, immunotherapy, and molecularly targeted agents. Recently completed and ongoing neuroblastoma clinical trials testing these novel treatments are highlighted. In addition, we discuss ongoing clinical trials designed to evaluate precision medicine approaches that target actionable somatic mutations and oncogenic cellular pathways. Expert opinion Advances in genomic medicine and molecular biology have led to the development of early phase studies testing biologically rational therapies targeting aberrantly activated cellular pathways. Because many of these drugs have a wider therapeutic index than standard chemotherapeutic agents, these treatments may be more effective and less toxic than current strategies. However, to effectively integrate these targeted strategies, robust predictive biomarkers must be developed that will identify patients who will benefit from these approaches and rapidly match treatments to patients at diagnosis.

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“…In a German Neuroblastoma Trial (NB97), a benefit of I-131 MIBG therapy at the end of induction therapy in neuroblastoma patients with residual disease was investigated [ 63 ]. After induction therapy for newly diagnosed patients, 36 patients received I-131 MIBG therapy before auto-HCT and 30 patients did not receive I-131 MIBG therapy before auto-HCT.…”

Section: I-131 Mibg Therapy For Newly Diagnosed Neuroblastomamentioning

confidence: 99%

Iodine‐131 Metaiodobenzylguanidine Therapy for Neuroblastoma: Reports So Far and Future Perspective

Kayano

Kinuya

2015

The Scientific World Journal

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Neuroblastoma, which derives from neural crest, is the most common extracranial solid cancer in childhood. The tumors express the norepinephrine (NE) transporters on their cell membrane and take in metaiodobenzylguanidine (MIBG) via a NE transporter. Since iodine-131 (I-131) MIBG therapy was firstly reported, many trails of MIBG therapy in patients with neuroblastoma were performed. Though monotherapy with a low dose of I-131 MIBG could achieve high-probability pain reduction, the objective response was poor. In contrast, more than 12 mCi/kg I-131 MIBG administrations with or without hematopoietic cell transplantation (HCT) obtain relatively good responses in patients with refractory or relapsed neuroblastoma. The combination therapy with I-131 MIBG and other modalities such as nonmyeloablative chemotherapy and myeloablative chemotherapy with HCT improved the therapeutic response in patients with refractory or relapsed neuroblastoma. In addition, I-131 MIBG therapy incorporated in the induction therapy was proved to be feasible in patients with newly diagnosed neuroblastoma. To expand more the use of MIBG therapy for neuroblastoma, further studies will be needed especially in the use at an earlier stage from diagnosis, in the use with other radionuclide formations of MIBG, and in combined use with other therapeutic agents.

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Is there a benefit of 131I-MIBG therapy in the treatment of children with stage 4 neuroblastoma?

Abstract: An independent advantage of I-131-MIBG therapy could not be proven in this retrospective analysis. The ongoing German Neuroblastoma Trial NB2004 will address the influence of (131)I-MIBG therapy with emphasis on tumour dosimetry.

Cited by 41 publications

References 25 publications

Promising Therapeutic Targets in Neuroblastoma

Promising Therapeutic Targets in Neuroblastoma

Emerging and investigational therapies for neuroblastoma

Iodine‐131 Metaiodobenzylguanidine Therapy for Neuroblastoma: Reports So Far and Future Perspective

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