BORON NEUTRON-CAPTURE THERAPY FOR GLIOBLASTOMA-MULTIFORME USING P-BORONOPHENYLALANINE AND EPITHERMAL NEUTRONS - TRIAL DESIGN AND EARLY CLINICAL-RESULTS
Ja. Coderre et al., BORON NEUTRON-CAPTURE THERAPY FOR GLIOBLASTOMA-MULTIFORME USING P-BORONOPHENYLALANINE AND EPITHERMAL NEUTRONS - TRIAL DESIGN AND EARLY CLINICAL-RESULTS, Journal of neuro-oncology, 33(1-2), 1997, pp. 141-152
A Phase I/II clinical trial of boron neutron capture therapy (BNCT) fo
r glioblastoma multiforme is underway using the amino acid analog p-bo
ronophenylalanine (BPA) and the epithermal neutron beam at the Brookha
ven Medical Research Reactor. Biodistribution studies were carried out
in 18 patients at the time of craniotomy using an i.v. infusion of BP
A, solubilized as a fructose complex (BPA-F). There were no toxic effe
cts 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/bloo
d 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 mu g B-10/g. The prescri
bed maximum dose to normal brain (1 cm(3) volume) was 10.5 photon-equi
valent 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 estimate
d 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 pati
ents 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 do
se escalation phase of this protocol.