A critical examination of the results from the Harvard-MIT NCT program phase I clinical trial of neutron capture therapy for intracranial disease

A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy ( NCT); tumor response was also followed as a secondary endpoint. Between July 1996 and May 1999, 24 subjects were entered into a phase I trial evaluating cranial NCT in subjects with primary or metastatic brain tumors. Two subjects were excluded due to a decline in their performance status and 22 subjects were irradiated at the MIT Nuclear Reactor Laboratory. The median age was 56 years ( range 24 - 78). All subjects had a pathologically confirmed diagnosis of either glioblastoma ( 20) or melanoma ( 2) and a Karnofsky of 70 or higher. Neutron irradiation was delivered with a 15 cm diameter epithermal beam. Treatment plans varied from 1 to 3 fields depending upon the size and location of the tumor. The B-10 carrier, L- p- boronophenylalanine- fructose ( BPA- f), was infused through a central venous catheter at doses of 250 mg kg(-1) over 1 h ( 10 subjects), 300 mg kg(-1) over 1.5 h ( two subjects), or 350 mg kg(-1) over 1.5 - 2 h ( 10 subjects). The pharmacokinetic profile of B-10 in blood was very reproducible and permitted a predictive model to be developed. Cranial NCT can be delivered at doses high enough to exhibit a clinical response with an acceptable level of toxicity. Acute toxicity was primarily associated with increased intracranial pressure; late pulmonary effects were seen in two subjects. Factors such as average brain dose, tumor volume, and skin, mucosa, and lung dose may have a greater impact on tolerance than peak dose alone. Two subjects exhibited a complete radiographic response and 13 of 17 evaluable subjects had a measurable reduction in enhanced tumor volume following NCT.