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

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.

• Authors: J A Coderre, E H Elowitz, M Chadha, R Bergland, J Capala, D D Joel, H B Liu, D N Slatkin, A D Chanana
• Journal: Journal of neuro-oncology (J Neurooncol) Vol. 33 Issue 1-2 Pg. 141-52 (May 1997) ISSN: 0167-594X [Print] United States
• PMID: 9151231 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Controlled Clinical Trial, Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Boron Compounds
• Phenylalanine
• 4-boronophenylalanine

Topics

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