Safety and Efficacy of Tandem (131)I-Metaiodobenzylguanidine Infusions in Relapsed/Refractory Neuroblastoma

University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Pediatric Blood & Cancer (Impact Factor: 2.39). 12/2011; 57(7):1124-9. DOI: 10.1002/pbc.23062
Source: PubMed


Targeted radiotherapy with (131) I-Metaiodobenzylguanidine ((131) I-MIBG) is safe and effective therapy for patients with relapsed neuroblastoma, but anti-tumor activity is sometimes transient. The goal of this study was to determine the safety and efficacy of early (<100 days) second (131) I-MIBG treatment following an effective initial treatment.
After an initial infusion of 18 mCi/kg (131) I-MIBG, patients with tumor response or stable disease (SD), and available hematopoietic stem cell product, were eligible for additional (131) I-MIBG therapy. Residual thrombocytopenia did not preclude patients from receiving additional treatment. Subsequent treatment was administered a minimum of 6 weeks and maximum 100 days from initial infusion, and subjects could receive subsequent therapy if the same criteria were met.
Seventy-six heavily pretreated patients (median 4 prior chemotherapy regimens, range 1-8) with relapsed neuroblastoma were treated with (131) I-MIBG. Response rate to the first infusion was 30%, with 49% showing SD. Response rate among the 41 patients receiving a subsequent second infusion was 29%. After two treatments, 39% of patients experienced a reduction in overall disease burden. Four of five complete responses (CRs) to the initial infusion were maintained, despite all five having disease readily apparent on immediate post-second treatment (131) I-MIBG scanning. Hematologic toxicity was managed with early PBSC support after the second therapy (median: 15 days).
Early second (131) I-MIBG safely reduces disease burden in patients with relapsed neuroblastoma. Patients with CR by conventional (123) I-MIBG scintigraphy may have substantial disease burden apparent on high-dose (131) I-MIBG scintigraphy, supporting consolidation with subsequent (131) I-MIBG therapy in cases of apparent complete remission. Pediatr Blood Cancer 2011; 57: 1124-1129. © 2011 Wiley Periodicals, Inc.

17 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neuroblastoma is an enigmatic disorder, being a pathological entity, but presenting clinically with a wide range of symptoms and responding to treatment in a plethora of different and sometimes unpredictable ways. This represents a challenge for those charged with diagnosing and treating the disease. It is a disease of young children, being the most common tumour in infants, with the prognosis worsening with increasing age at presentation. There are no particular risk factors, so the diagnosis depends on clinical examination and appropriate investigations. Once the diagnosis has been made, further staging investigations and risk stratification are undertaken prior to commencing treatment. Once identified, high-risk disease remains the greatest challenge, with many of these cases ultimately relapsing. Treatment is best undertaken within a specialist, multidisciplinary team, with many medical specialties and allied health professionals involved, in order to optimize the progress and outcome. With high-risk disease being so aggressive, so does the treatment need to be. There are new treatment modalities available which are associated with significant side and late effects. The challenge is how to bring these into the current treatment regimens in order to reduce the relapse rate without causing excessive harm.
    Paediatrics and Child Health 03/2012; 22(3). DOI:10.1016/j.paed.2011.08.005
  • [Show abstract] [Hide abstract]
    ABSTRACT: Since 1981, meta-iodobenzylguanidine (MIBG), labeled with (131)I and later (123)I, has become a valuable agent in the diagnosis and therapy of a number of endocrine tumors. Initially, the agent located pheochromocytomas and paragangliomas (PGLs), both sporadic and familial, in multiple anatomic sites; surgeons were thereby guided to excisional therapies, which were previously difficult and sometimes impossible. The specificity in diagnosis has remained above 95%, but sensitivity has varied with the nature of the tumor: close to 90% for intra-adrenal pheochromocytomas but 70% or less for PGLs. For patients with neuroblastoma, carcinoid tumors, and medullary thyroid carcinoma, imaging with radiolabeled MIBG portrays important diagnostic evidence, but for these neoplasms, use has been primarily as an adjunct to therapy. Although diagnosis by radiolabeled MIBG has been supplemented and sometimes surpassed by newer scintigraphic agents, searches by this radiopharmaceutical remain indispensable for optimal care of some patients. The radiation imparted by concentrations of (131)I-MIBG in malignant pheochromocytomas, PGLs, carcinoid tumors, and medullary thyroid carcinoma has reduced tumor volumes and lessened excretions of symptom-inflicting hormones, but its value as a therapeutic agent is being fulfilled primarily in attacks on neuroblastomas, which are scourges of children. Much promise has been found in tumor disappearance and prolonged survival of treated patients. The experiences with therapeutic (131)I-MIBG have led to development of new tactics and strategies and to well-founded hopes for elimination of cancers. Radiolabeled MIBG is an exemplar of theranostics and remains a worthy agent for both diagnosis and therapy of endocrine tumors.
    Seminars in nuclear medicine 05/2012; 42(3):171-84. DOI:10.1053/j.semnuclmed.2011.11.004 · 3.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neuroblastoma is the most common extra-cranial solid tumor in children. It is a heterogeneous disease, consisting of neural crest-derived tumors with remarkably different clinical behaviors. It can present in a wide variety of ways, including lesions which have the potential to spontaneously regress, or as an extremely aggressive form of metastatic cancer which is resistant to all forms of modern therapy. They can arise anywhere along the sympathetic nervous system. The median age of presentation is approximately 18 months of age. Urinary catecholamines (HVA and VMA) are extremely sensitive and specific tumor markers and are used in diagnosis, treatment response assessment and post-treatment surveillance. The largest national treatment groups from North America, Europe and Japan have formed the International Neuroblastoma Risk Group Task Force (INRG) to identify prognostic factors, to understand the mechanisms of tumorigenesis in this rare disease and to develop multi-modality therapies to improve outcomes and decrease treatment-related toxicities. This international cooperation has resulted in a significant leap in our understanding of the molecular pathogenesis of neuroblastoma. Lower staged disease can be cured if the lesion is resectable. Treatment of unresectable disease (loco-regional and metastatic) is stratified depending on clinical features (age at presentation, staging investigations) and specific tumor biological markers that include histopathological analyses, chromosomal abnormalities and the quantification of expression of an oncogene (MYCN). Modern treatment of high-risk neuroblastoma is the paradigm for the evolution of therapy in pediatric oncology. Outcomes have improved substantially with multi-modality therapy, including chemotherapy, surgery, radiation therapy, myeloablative therapy with stem cell transplant, immunotherapy and differentiation therapy; these comprise the standard of care worldwide. In addition, newer targeted therapies are being tested in phase I/II trials. If successful these agents will be incorporated into mainstream treatment programs.
    Critical Reviews in Clinical Laboratory Sciences 05/2012; 49(3):85-115. DOI:10.3109/10408363.2012.683483 · 3.69 Impact Factor
Show more