Neutron capture therapy (NCT) is a unique form of radiation due to the combination of high linear energy transfer (LET) properties and biological targeting. Extensive preclinical work and early clinical experiences have shown NCT to be active against melanoma, and glioblastoma, diseases poorly controlled by conventional radiation. This phase I/II trial is designed to determine the maximum tolerated dose (MTD) for cranial NCT irradiation, an important parameter for future clinical trials. Sixteen patients with either metastatic melanoma or biopsy proven glioblastoma multiforme will be entered. A standard dose escalation scheme will be employed, 3 patients per dose cohort, 10 percent increase in normal tissue dose per cohort. The starting point will be a volume average brain dose of 7.0 RBE-Gy given in two fractions. Boron-delivery will be through the use of l-p-boronophenylalanine-fructose (BPA-f), 14 grams/meter-squared IV, over 90 minutes. Neutron irradiation will take place at the newly constructed fission converter beam (FCB) medical facility at the MIT Nuclear Reactor Laboratory. The FCB produces a high intensity epithermal neutron fluence with a low level of contamination that approaches theoretical limits. The clinical impact is in a greatly increased therapeutic gain. The following are the specific research objectives for the two-year period: (1.) To categorize the time course, uniformity and severity of acute and chronic normal tissue reactions following cranial NCT using the newly constructed fission converter beam (FCB) facility. (2.) To determine a maximum tolerated dose (MTD) for cranial NCT. (3.) To examine, through serial objective measurements, the clinical response of metastatic melanoma nodules and glioblastoma multiforme following NCT. (4.) To further the level of understanding of the pharmacokinetics of 1 -boronophenylalanine-fructose (BPA-f) through the measurement of blood and plasma concentrations of 10B and the refinement of the predictive accuracy of a two-compartment pharmacokinetic model developed by this research group. The long-term objective is to integrate NCT into the established therapeutic mainstream for melanoma, primary brain tumors, and other malignancies.
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