Arsenic Trioxide as a Radiation Sensitizer for 131I-Metaiodobenzylguanidine Therapy: Results of a Phase II Study. Academic Article uri icon

Overview

MeSH

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Male
  • Survival Analysis
  • Treatment Outcome

MeSH Major

  • 3-Iodobenzylguanidine
  • Adrenal Gland Neoplasms
  • Arsenicals
  • Brain Neoplasms
  • Neuroblastoma
  • Oxides
  • Paraganglioma
  • Pheochromocytoma
  • Radiation-Sensitizing Agents
  • Radiopharmaceuticals

abstract

  • Arsenic trioxide has in vitro and in vivo radiosensitizing properties. We hypothesized that arsenic trioxide would enhance the efficacy of the targeted radiotherapeutic agent (131)I-metaiodobenzylguanidine ((131)I-MIBG) and tested the combination in a phase II clinical trial. Patients with recurrent or refractory stage 4 neuroblastoma or metastatic paraganglioma/pheochromocytoma (MP) were treated using an institutional review board-approved protocol (Clinicaltrials.gov identifier NCT00107289). The planned treatment was (131)I-MIBG (444 or 666 MBq/kg) intravenously on day 1 plus arsenic trioxide (0.15 or 0.25 mg/m(2)) intravenously on days 6-10 and 13-17. Toxicity was evaluated using National Cancer Institute Common Toxicity Criteria, version 3.0. Response was assessed by International Neuroblastoma Response Criteria or (for MP) by changes in (123)I-MIBG or PET scans. Twenty-one patients were treated: 19 with neuroblastoma and 2 with MP. Fourteen patients received (131)I-MIBG and arsenic trioxide, both at maximal dosages; 2 patients received a 444 MBq/kg dose of (131)I-MIBG plus a 0.15 mg/kg dose of arsenic trioxide; and 3 patients received a 666 MBq/kg dose of (131)I-MIBG plus a 0.15 mg/kg dose of arsenic trioxide. One did not receive arsenic trioxide because of transient central line-induced cardiac arrhythmia, and another received only 6 of 10 planned doses of arsenic trioxide because of grade 3 diarrhea and vomiting with concurrent grade 3 hypokalemia and hyponatremia. Nineteen patients experienced myelosuppression higher than grade 2, most frequently thrombocytopenia (n = 18), though none required autologous stem cell rescue. Twelve of 13 evaluable patients experienced hyperamylasemia higher than grade 2 from transient sialoadenitis. By International Neuroblastoma Response Criteria, 12 neuroblastoma patients had no response and 7 had progressive disease, including 6 of 8 entering the study with progressive disease. Objective improvements in semiquantitative (131)I-MIBG scores were observed in 6 patients. No response was seen in MP. Seventeen of 19 neuroblastoma patients continued on further chemotherapy or immunotherapy. Mean 5-year overall survival (±SD) for neuroblastoma was 37% ± 11%. Mean absorbed dose of (131)I-MIBG to blood was 0.134 cGy/MBq, well below myeloablative levels in all patients. (131)I-MIBG plus arsenic trioxide was well tolerated, with an adverse event profile similar to that of (131)I-MIBG therapy alone. The addition of arsenic trioxide to (131)I-MIBG did not significantly improve response rates when compared with historical data with (131)I-MIBG alone. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

publication date

  • February 2016

has subject area

  • 3-Iodobenzylguanidine
  • Adolescent
  • Adrenal Gland Neoplasms
  • Adult
  • Arsenicals
  • Brain Neoplasms
  • Child
  • Child, Preschool
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Male
  • Neuroblastoma
  • Oxides
  • Paraganglioma
  • Pheochromocytoma
  • Radiation-Sensitizing Agents
  • Radiopharmaceuticals
  • Survival Analysis
  • Treatment Outcome

Research

keywords

  • Clinical Trial, Phase II
  • Journal Article
  • Randomized Controlled Trial

Identity

Language

  • eng

PubMed Central ID

  • PMC4976822

Digital Object Identifier (DOI)

  • 10.2967/jnumed.115.161752

PubMed ID

  • 26742708

Additional Document Info

start page

  • 231

end page

  • 237

volume

  • 57

number

  • 2