A phase-I clinical trial for cranial BNCT at Harvard-MIT

Phase I trial designed to determine the maximum tolerable dose to normal tissue for cranial BNCT (Boron Neutron Capture Therapy) irradiations was recently completed at Harvard Medical School and MIT. Twenty-two subjects diagnosed with either glioblastoma multiforme or intracranial melanoma were treated between 1996 and 1999. Subjects received either one or two administrations of boronophenylalanine intravenously at doses between 250 and 350 mg/kg body weight, then exposed in one, two or three fields to epithermal neutrons at the MIT Research Reactor in one or two fractions. Over the course of the study, the maximum normal tissue dose target was increased from 8.8 to 14.2 RBE (Relative Biological Effectiveness) Gy in 10% increments. Subjects have been followed clinically and radiographically. Of those patients surviving beyond six months, no MRI (Magnetic Resonance Image) white-matter changes were observed and no long-term complications attributable to BNCT were evident. Tumor responses were observed, particularly with the melanoma subjects. With increasing doses, difficulties arose from long irradiation times (approximately 3 hours) and the emergence of acute reactions in the skin and mucosa. The trial was stopped in May 1999. Future trials will be initiated with the new high intensity, low background fission converter beam at MIT. (author)