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

J Neurooncol. Mar-Apr 2003;62(1-2):111-21. doi: 10.1007/BF02699938.

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 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 10B 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 10B 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Boron / blood
  • Boron / pharmacokinetics*
  • Boron Neutron Capture Therapy / adverse effects*
  • Brain Neoplasms / radiotherapy*
  • Brain Neoplasms / secondary
  • Dose-Response Relationship, Radiation
  • Glioblastoma / radiotherapy*
  • Humans
  • Maximum Tolerated Dose*
  • Melanoma / radiotherapy*
  • Middle Aged
  • Radiotherapy Dosage
  • Radiotherapy Planning, Computer-Assisted
  • Treatment Outcome

Substances

  • Boron