title: 131I-metaiodobenzylguanidine with intensive chemotherapy and autologous stem cell transplantation for high-risk neuroblastoma. A new approaches to neuroblastoma therapy (NANT) phase II study.
abstract: (131)I-Metaiodobenzylguanidine ((131)I-MIBG) has been used as a single agent or in combination with chemotherapy for the treatment of high-risk neuroblastoma. The activity and toxicity of (131)I-MIBG when combined with carboplatin, etoposide, and melphalan (CEM) and autologous stem cell transplantation (SCT) are now investigated in a phase II multicenter study. Fifty patients with MIBG-avid disease were enrolled into 2 cohorts, stratified by response to induction therapy. The primary study endpoint was response of patients with refractory (n = 27) or progressive disease (n = 15). A second cohort of patients (n = 8) with a partial response (PR) to induction therapy was included to obtain preliminary response data. (131)I-MIBG was administered on day -21 to all patients, with CEM given days -7 to -4, and SCT given on day 0. (131)I-MIBG dosing was determined by pre-therapy glomerular filtration rate (GFR), with 8 mCi/kg given if GFR was 60 to 99 mL/minute/1.73 m(2) (n = 13) and 12 mCi/kg if GFR ≥ 100 mL/minute/1.73 m(2) (n = 37). External beam radiotherapy was delivered to the primary and metastatic sites, beginning approximately 6 weeks after SCT. Responses (complete response + PR) were seen in 4 of 41 (10%) evaluable patients with primary refractory or progressive disease. At 3 years after SCT, the event-free survival (EFS) was 20% ± 7%, with overall survival (OS) 62% ± 8% for this cohort of patients. Responses were noted in 3 of 8 (38%) of patients with a PR to induction, with 3-year EFS 38% ± 17% and OS 75% ± 15%. No statistically significant difference was found comparing EFS or OS based upon pre-therapy GFR or disease cohort. Six of 50 patients had nonhematologic dose-limiting toxicity (DLT); 1 of 13 in the low GFR and 5 of 37 in the normal GFR cohorts. Hepatic sinusoidal obstructive syndrome (SOS) was seen in 6 patients (12%), with 5 events defined as dose-limiting SOS. The median times to neutrophil and platelet engraftment were 10 and 15 days, respectively. Patients received a median 163 cGy (61 to 846 cGy) with (131)I-MIBG administration, with 2 of 3 patients receiving >500 cGy experiencing DLT. The addition of (131)I-MIBG to a myeloablative CEM regimen is tolerable and active therapy for patients with high-risk neuroblastoma.
authors: Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, Michigan. Electronic address: gyanik@umich.edu.
authors: Gregory A
authors: GA
authors: Yanik
authors: Department of Pediatrics, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles, California.
authors: Judith G
authors: JG
authors: Villablanca
authors: Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania.
authors: John M
authors: JM
authors: Maris
authors: Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Brian
authors: B
authors: Weiss
authors: Department of Preventive Medicine, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles, California; USC/Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles, California.
authors: Susan
authors: S
authors: Groshen
authors: Department of Pediatrics, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles, California.
authors: Araz
authors: A
authors: Marachelian
authors: Department of Pediatrics, Seattle Children's Hospital/University of Washington School of Medicine, Seattle, Washington.
authors: Julie R
authors: JR
authors: Park
authors: USC/Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles, California.
authors: Denice
authors: D
authors: Tsao-Wei
authors: Department of Radiology, University of California San Francisco, San Francisco, California.
authors: Randall
authors: R
authors: Hawkins
authors: Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors: Barry L
authors: BL
authors: Shulkin
authors: Department of Radiology, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles, California.
authors: Hollie
authors: H
authors: Jackson
authors: Department of Radiology, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles, California.
authors: Fariba
authors: F
authors: Goodarzian
authors: Department of Pathology, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles, California.
authors: Hiro
authors: H
authors: Shimada
authors: Department of Radiology, University of California San Francisco, San Francisco, California.
authors: Jesse
authors: J
authors: Courtier
authors: Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, Michigan.
authors: Raymond
authors: R
authors: Hutchinson
authors: Department of Pediatrics, University of California San Francisco, San Francisco, California.
authors: Daphne
authors: D
authors: Haas-Koga
authors: Department of Pediatrics, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles, California.
authors: C Beth
authors: CB
authors: Hasenauer
authors: Department of Pediatrics, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles, California.
authors: Scarlett
authors: S
authors: Czarnecki
authors: Department of Pediatrics, Vanderbilt University, Nashville, Tennessee.
authors: Howard M
authors: HM
authors: Katzenstein
authors: Department of Pediatrics, University of California San Francisco, San Francisco, California.
authors: Katherine K
authors: KK
authors: Matthay
mesh_terms: D019797:3-Iodobenzylguanidine / Q000008:administration & dosage*; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D064592:Autografts; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009447:Neuroblastoma / Q000401:mortality / Q000628:therapy*; D061766:Proton Therapy; D033581:Stem Cell Transplantation
chemical_list: D000970:Antineoplastic Agents; D019797:3-Iodobenzylguanidine
keywords: Metaiodobenzylguanidine (MIBG); Neuroblastoma; Transplantation