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

Abstract

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 1 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. The10B 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 of10B 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.

DOI: 10.1007/BF02699938

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@article{Busse2003ACE, title={A critical examination of the results from the Harvard-MIT NCT program phase I clinical trial of neutron capture therapy for intracranial disease}, author={Paul M. Busse and Otto K. Harling and Matthew R. Palmer and W. S. Kiger and Jody Kaplan and Irving D. Kaplan and Cynthia Fu-Yu Chuang and J. Tim Goorley and Kent J. Riley and Thomas H . Newton and Gustavo Cruz and Xing-Qi Lu and Robert G. Zamenhof}, journal={Journal of Neuro-Oncology}, year={2003}, volume={62}, pages={111-121} }