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

  • Paul M. Busse
  • Otto K. Harling
  • Matthew R. Palmer
  • W. S. Kiger
  • Jody Kaplan
  • Irving Kaplan
  • Cynthia F. Chuang
  • J. Tim Goorley
  • Kent J. Riley
  • Thomas H. Newton
  • Gustavo A. Santa Cruz
  • Xing-Qi Lu
  • Robert G. Zamenhof
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

Authors and Affiliations

  • Paul M. Busse
    • 1
  • Otto K. Harling
    • 3
  • Matthew R. Palmer
    • 2
  • W. S. Kiger
    • 1
  • Jody Kaplan
    • 1
  • Irving Kaplan
    • 1
  • Cynthia F. Chuang
    • 3
  • J. Tim Goorley
    • 3
  • Kent J. Riley
    • 3
  • Thomas H. Newton
    • 3
  • Gustavo A. Santa Cruz
    • 4
  • Xing-Qi Lu
    • 1
  • Robert G. Zamenhof
    • 2
  1. 1.Department of Radiation OncologyBeth Israel Deaconess Medical CenterBostonUSA
  2. 2.Department of RadiologyBeth Israel Deaconess Medical Center, Harvard Medical SchoolBoston
  3. 3.Nuclear Reactor LaboratoryMassachusetts Institute of TechnologyCambridgeUSA
  4. 4.Comisión Nacional de Energía AtómicaBuenos AiresArgentina