Boron neutron capture therapy for glioblastoma multiforme: Interim resultsfrom the Phase I/II dose-escalation studies

OBJECTIVE: The primary objective of these Phase I/II dose-escalation studie s is to evaluate the safety of borono-phenylalanine (BPA) -fructose-mediate d boron neutron capture therapy (BNCT) for patients with glioblastoma multi forme (GBM). A secondary purpose is to assess the palliation of GEM by BNCT , if possible. METHODS: Thirty-eight patients with GBM have been treated. Subtotal or gros s total resection of GBM was performed for 38 patients (median age, 56 yr) before BNCT. BPA-fructose (250 or 290 mg BPA/kg body weight) was infused in travenously, in 2 hours, approximately 3 to 5 weeks after surgery. Neutron irradiation was begun between 34 and 82 minutes after the end of the BPA in fusion and lasted 38 to 65 minutes. RESULTS: Toxicity related to BPA-fructose was not observed. The maximal rad iation dose to normal brain varied from 8.9 to 14.8 Gy-Eq. The volume-weigh ted average radiation dose to normal brain tissues ranged from 1.9 to 6.0 G y-Eq. No BNCT-related Grade 3 or 4 toxicity was observed, although milder t oxicities were seen. Twenty-five of 37 assessable patients are dead, all as a result of progressive GEM. No radiation-induced damage to normal brain t issue was observed in postmortem examinations of seven brains. The minimal tumor volume doses ranged from 18 to 55 Gy-Eq. The median time to tumor pro gression and the median survival time from diagnosis (from Kaplan-Meier cur ves) were 31.6 weeks and 13.0 months, respectively. CONCLUSION: The BNCT procedure used has been safe for all patients treated to date. Our limited clinical evaluation suggests that the palliation offer ed by a single session of BNCT is comparable to that provided by fractionat ed photon therapy. Additional studies with further escalation of radiation doses are in progress.