Journal of Neuro-Oncology

, Volume 62, Issue 1, pp 111–121

A critical examination of the results from the Harvard-MIT NCT program phase I clinical trial of neutron capture therapy for intracranial disease

Authors

    • Department of Radiation OncologyBeth Israel Deaconess Medical Center
  • Otto K. Harling
    • Nuclear Reactor LaboratoryMassachusetts Institute of Technology
  • Matthew R. Palmer
    • Department of RadiologyBeth Israel Deaconess Medical Center, Harvard Medical School
  • W. S. Kiger
    • Department of Radiation OncologyBeth Israel Deaconess Medical Center
  • Jody Kaplan
    • Department of Radiation OncologyBeth Israel Deaconess Medical Center
  • Irving Kaplan
    • Department of Radiation OncologyBeth Israel Deaconess Medical Center
  • Cynthia F. Chuang
    • Nuclear Reactor LaboratoryMassachusetts Institute of Technology
  • J. Tim Goorley
    • Nuclear Reactor LaboratoryMassachusetts Institute of Technology
  • Kent J. Riley
    • Nuclear Reactor LaboratoryMassachusetts Institute of Technology
  • Thomas H. Newton
    • Nuclear Reactor LaboratoryMassachusetts Institute of Technology
  • Gustavo A. Santa Cruz
    • Comisión Nacional de Energía Atómica
  • Xing-Qi Lu
    • Department of Radiation OncologyBeth Israel Deaconess Medical Center
  • Robert G. Zamenhof
    • Department of RadiologyBeth Israel Deaconess Medical Center, Harvard Medical School
Article

DOI: 10.1007/BF02699938

Cite this article as:
Busse, P.M., Harling, O.K., Palmer, M.R. et al. J Neuro-Oncol (2003) 62: 111. doi:10.1007/BF02699938

Summary

A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT); tumor response was also followed as a secondary endpoint. Between July 1996 and May 1999, 24 subjects were entered into a phase 1 trial evaluating cranial NCT in subjects with primary or metastatic brain tumors. Two subjects were excluded due to a decline in their performance status and 22 subjects were irradiated at the MIT Nuclear Reactor Laboratory. The median age was 56 years (range 24–78). All subjects had a pathologically confirmed diagnosis of either glioblastoma (20) or melanoma (2) and a Karnofsky of 70 or higher. Neutron irradiation was delivered with a 15 cm diameter epithermal beam. Treatment plans varied from 1 to 3 fields depending upon the size and location of the tumor. The10B carrier,l-p-boronophenylalanine-fructose (BPA-f), was infused through a central venous catheter at doses of 250 mg kg−1 over 1 h (10 subjects), 300 mg kg−1 over 1.5 h (two subjects), or 350 mg kg−1 over 1.5–2 h (10 subjects). The pharmacokinetic profile of10B in blood was very reproducible and permitted a predictive model to be developed. Cranial NCT can be delivered at doses high enough to exhibit a clinical response with an acceptable level of toxicity. Acute toxicity was primarily associated with increased intracranial pressure; late pulmonary effects were seen in two subjects. Factors such as average brain dose, tumor volume, and skin, mucosa, and lung dose may have a greater impact on tolerance than peak dose alone. Two subjects exhibited a complete radiographic response and 13 of 17 evaluable subjects had a measurable reduction in enhanced tumor volume following NCT.

Key words

BNCTglioblastomamelanomaclinical trialboronophenylalanine-fructose (BPA-f)

Copyright information

© Kluwer Academic Publishers 2003