title: 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.affiliation: Medical Department Brookhaven National Laboratory, Upton, NY 11973, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Coderre
authors.forename: E H
authors.initials: EH
authors.lastname: Elowitz
authors.forename: M
authors.initials: M
authors.lastname: Chadha
authors.forename: R
authors.initials: R
authors.lastname: Bergland
authors.forename: J
authors.initials: J
authors.lastname: Capala
authors.forename: D D
authors.initials: DD
authors.lastname: Joel
authors.forename: H B
authors.initials: HB
authors.lastname: Liu
authors.forename: D N
authors.initials: DN
authors.lastname: Slatkin
authors.forename: A D
authors.initials: AD
authors.lastname: Chanana
mesh_terms: D000328:Adult; D001896:Boron Compounds / Q000009:adverse effects / Q000493:pharmacokinetics*; D016754:Boron Neutron Capture Therapy / Q000009:adverse effects; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000175:diagnosis / Q000532:radiotherapy* / Q000601:surgery; D005909:Glioblastoma / Q000175:diagnosis / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D008279:Magnetic Resonance Imaging; D009502:Neutrons; D009688:Nuclear Reactors; D010649:Phenylalanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D001896:Boron Compounds; D010649:Phenylalanine; C033685:4-boronophenylalanine