Phase 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

• Published in: Journal of clinical oncology Vol. 24; no. 3; pp. 500 - 506
• Main Authors: MATTHAY, Katherine K, TAN, Jessica C, SEEGER, Robert C, MARIS, John M, VILLABLANCA, Judith G, YANIK, Gregory A, VEATCH, Janet, FRANC, Benjamin, TWOMEY, Eilish, HORN, Biljana, REYNOLDS, C. Patrick, GROSHEN, Susan
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 20.01.2006; Lippincott Williams & Wilkins
• Subjects: 3-Iodobenzylguanidine - administration & dosage; 3-Iodobenzylguanidine - adverse effects; Adolescent; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Carboplatin - administration & dosage; Child; Child, Preschool; Disease-Free Survival; Drug Administration Schedule; Etoposide - administration & dosage; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Medical sciences; Melphalan - administration & dosage; Neuroblastoma - drug therapy; Neuroblastoma - surgery; Neurology; Survival Analysis; Transplantation, Autologous; Treatment Outcome; Tumors; Tumors of the nervous system. Phacomatoses; Nervous system diseases; Treatment resistance; Iodine 131; Stem cell; Hematopoietic cell; Malignant tumor; Neuroblastoma; Increasing dose; Autograft; Chemotherapy; Cancerology; Treatment; Graft; Myelosuppression; Autonomic neuropathy
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2005.03.6400

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.