Boron neutron capture therapy for glioblastoma multiforme using p-boronophenylalanine and epithermal neutrons: trial design and early clinical results

J Neurooncol. 1997 May;33(1-2):141-52. doi: 10.1023/a:1005741919442.

Abstract

A Phase I/II clinical trial of boron neutron capture therapy (BNCT) for glioblastoma multiforme is underway using the amino acid analog p-boronophenylalanine (BPA) and the epithermal neutron beam at the Brook-haven Medical Research Reactor. Biodistribution studies were carried out in 18 patients at the time of craniotomy using an i.v. infusion of BPA, solubilized as a fructose complex (BPA-F). There were no toxic effects related to the BPA-F administration at doses of 130, 170, 210, or 250 mg BPA/kg body weight. The tumor/ blood, brain/blood and scalp/blood boron concentration ratios were approximately 3.5:1, 1:1 and 1.5:1, respectively. Ten patients have received BNCT following 2-hr infusions of 250 mg BPA/kg body weight. The average boron concentration in the blood during the irradiation was 13.0 +/- 1.5 micrograms 10B/g. The prescribed maximum dose to normal brain (1 cm3 volume) was 10.5 photon-equivalent Gy (Gy-Eq). Estimated maximum and minimum doses (mean +/- sd, n = 10) to the tumor volume were 52.6 +/- 4.9 Gy-Eq (range: 64.4-47.6) and 25.2 +/- 4.2 Gy-Eq (range: 32.3-20.0), respectively). The estimated minimum dose to the target volume (tumor +2 cm margin) was 12.3 +/- 2.7 Gy-Eq (range: 16.2-7.8). There were no adverse effects on normal brain. The scalp showed mild erythema, followed by epilation in the 8 cm diameter field. Four patients developed recurrent tumor, apparently in the lower dose (deeper) regions of the target volume, at post-BNCT intervals of 7,5,3.5 and 3 months, respectively. The remaining patients have had less than 4 months of post-BNCT follow-up. BNCT, at this starting dose level, appears safe. Plans are underway to begin the dose escalation phase of this protocol.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Controlled Clinical Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Boron Compounds / adverse effects
  • Boron Compounds / pharmacokinetics*
  • Boron Neutron Capture Therapy* / adverse effects
  • Brain / pathology
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / radiotherapy*
  • Brain Neoplasms / surgery
  • Glioblastoma / diagnosis
  • Glioblastoma / radiotherapy*
  • Glioblastoma / surgery
  • Humans
  • Magnetic Resonance Imaging
  • Neutrons
  • Nuclear Reactors
  • Phenylalanine / adverse effects
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / pharmacokinetics
  • Tissue Distribution

Substances

  • Boron Compounds
  • Phenylalanine
  • 4-boronophenylalanine