Matthay KK, Tan JC, Villablanca JG, Yanik GA, Veatch J, Franc B, Twomey E, Horn B, Reynolds CP, Groshen S, Seeger RC, Maris JMPhase I dose escalation of iodine-131-metaiodobenzylguanidine with myeloablative chemotherapy and autologous stem-cell transplantation in refractory neuroblastoma: a new approaches to Neuroblastoma Therapy Consortium Study. J Clin Oncol 24: 500-506

The Children's Hospital of Philadelphia, Filadelfia, Pennsylvania, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 02/2006; 24(3):500-6. DOI: 10.1200/JCO.2005.03.6400
Source: PubMed


To determine the maximum-tolerated dose (MTD) and toxicity of iodine-131-metaiodobenzylguanidine ((131)I-MIBG) with carboplatin, etoposide, melphalan (CEM) and autologous stem-cell transplantation (ASCT) in refractory neuroblastoma.
Twenty-four children with primary refractory neuroblastoma and no prior ASCT were entered; 22 were assessable for toxicity and response. (131)I-MIBG was administered on day -21, CEM was administered on days -7 to -4, and ASCT was performed on day 0, followed by 13-cis-retinoic acid. (131)I-MIBG was escalated in groups of three to six patients, stratified by corrected glomerular filtration rate (GFR).
The MTD for patients with normal GFR (> or = 100 mL/min/1.73 m2) was 131I-MIBG 12 mCi/kg, carboplatin 1,500 mg/m2, etoposide 1,200 mg/m2, and melphalan 210 mg/m2. In the low-GFR cohort, at the initial dose level using 12 mCi/kg of 131I-MIBG and reduced chemotherapy, one in six patients had dose limiting toxicity (DLT), including veno-occlusive disease (VOD). Three more patients in this group had grade 3 or 4 hepatotoxicity, and two had VOD, without meeting DLT criteria. There was only one death as a result of toxicity among all 24 patients. All assessable patients engrafted, with median time for neutrophils > or = 500/microL of 10 days and median time for platelets > or = 20,000/microL of 26 days. Six of 22 assessable patients had complete or partial response, and 15 patients had mixed response or stable disease. The estimated probability of event-free survival and survival from the day of MIBG infusion for all patients at 3 years was 0.31 +/- 0.10 and 0.58 +/- 0.10, respectively.
131I-MIBG with myeloablative chemotherapy is feasible and effective for patients with neuroblastoma exhibiting de novo resistance to chemotherapy.

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    • "Therefore, recently, investigators have incorporated 131I-MIBG treatment into HDCT/autoSCT18,19). This therapy has been feasible and effective at 12 mCi/kg 131I-MIBG, and HDCT doses minimally decreased from those without 131I-MIBG treatment18). A phase II study is currently underway for the treatment of newly diagnosed high-risk NB, but not for relapsed tumors. "
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    ABSTRACT: Although high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) have improved the prognosis for patients with high-risk neuroblastoma (NB), event-free survival rates remain in the range of 30 to 40%, which is unsatisfactory. To further improve outcomes, several clinical trials, including tandem HDCT/autoSCT, high-dose (131)I-metaiodobenzylguanidine treatment, and immunotherapy with NB specific antibody, have been undertaken and pilot studies have reported encouraging results. Nonetheless, about half of high-risk NB patients still experience treatment failure and have no realistic chance for cure with conventional treatment options alone after relapse. Therefore, a new modality of treatment is warranted for these patients. In recent years, several groups of investigators have examined the feasibility and effectiveness of reduced-intensity allogeneic stem cell transplantation (RI alloSCT) for the treatment of relapsed/progressed NB. Although a graft-versus-tumor effect has not yet been convincingly demonstrated in the setting of relapsed NB, the strategy of employing RI alloSCT has provided hope that treatment-related mortality will be reduced and a therapeutic benefit will emerge. However, alloSCT for NB is still investigational and there remain many issues to be elucidated in many areas. At present, alloSCT is reserved for specific clinical trials testing the immunomodulatory effect against NB.
    Korean Journal of Pediatrics 04/2012; 55(4):115-20. DOI:10.3345/kjp.2012.55.4.115
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    • "There is strong rationale for the use of 123I-mIBG scintigraphy in assessing response to therapy, as it provides a very sensitive marker of unsuspected skeletal and nodal disease and functional evidence of residual active tumour. With the widespread use of therapeutic 131I-mIBG as a targeted radiopharmaceutical treatment of neuroblastoma both in newly diagnosed and relapsed patients, diagnostic mIBG scans will determine the eligibility for this modality (Garaventa et al, 1999; Gaze et al, 2005; Matthay et al, 2006, 2007; de Kraker et al, 2008; DuBois and Matthay, 2008). Previous studies have indicated that a positive mIBG scan after induction chemotherapy or just before myeloablative therapy may be a prognostic marker for a high likelihood of relapse (Ladenstein et al, 1998; Perel et al, 1999; Schmidt et al, 2008). "
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    ABSTRACT: Neuroblastoma is an embryonic tumour of the sympathetic nervous system, metastatic in half of the patients at diagnosis, with a high preponderance of osteomedullary disease, making accurate evaluation of metastatic sites and response to therapy challenging. Metaiodobenzylguanidine (mIBG), taken into cells via the norepinephrine transporter, provides a sensitive and specific method of assessing tumour in both soft tissue and bone sites. The goal of this report was to develop consensus guidelines for the use of mIBG scans in staging, response assessment and surveillance in neuroblastoma. The International Neuroblastoma Risk Group (INRG) Task Force, including a multidisciplinary group in paediatric oncology of North and South America, Europe, Oceania and Asia, formed a subcommittee on metastatic disease evaluation, including expert nuclear medicine physicians and oncologists, who developed these guidelines based on their experience and the medical literature, with approval by the larger INRG Task Force. Guidelines for patient preparation, radiotracer administration, techniques of scanning including timing, energy, specific views, and use of single photon emission computed tomography are included. Optimal timing of scans in relation to therapy and for surveillance is reviewed. Validated semi-quantitative scoring methods in current use are reviewed, with recommendations for use in prognosis and response evaluation. Metaiodobenzylguanidine scans are the most sensitive and specific method of staging and response evaluation in neuroblastoma, particularly when used with a semi-quantitative scoring method. Use of the optimal techniques for mIBG in staging and response, including a semi-quantitative score, is essential for evaluation of the efficacy of new therapy.
    British Journal of Cancer 04/2010; 102(9):1319-26. DOI:10.1038/sj.bjc.6605621 · 4.84 Impact Factor
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    ABSTRACT: Neuroblastomas are the most common malignant tumors in infancy and are second only to brain tumors as the type of solid malignancy seen during the first decade of life. They originate from neural crest cells that normally give rise to the adrenal medulla and the sympathetic ganglia. These cells, called cympathogonia, are pluripotential and may develop into ganglion cells, pheochromocytes, or neurofibrous tissue. Tumors derived from this tissue reflect the different stages of maturation or differentiation of normal neural crest cells. They include neuroblastoma (sympathoblastoma), ganglioneuroblastoma, ganglioneuroma, pheochromocytoma, and neurofibroma. Although the neuroblastoma was first described more than a century ago, it remains the most challenging childhood cancer to the pediatric oncologist because of its unusual and unpredictable biologic behavior and its resistance to therapy.
    Pediatric Clinics of North America 07/1985; 32(3):755-78. · 2.12 Impact Factor
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