Tissue uptake of BSH in patients with glioblastoma in the EORTC 11961 phase I BNCT trial

J Neurooncol. Mar-Apr 2003;62(1-2):145-56. doi: 10.1007/BF02699941.

Abstract

Purpose: The uptake of the boron compound Na2B12H10-SH (BSH) in tumor and normal tissues was investigated in the frame of the EORTC phase I trial 'Postoperative treatment of glioblastoma with BNCT at the Petten Irradiation Facility' (protocol 11961).

Methods and materials: The boron concentration in blood, tumor, normal brain, dura, muscle, skin and bone was detected using inductively coupled plasma-atomic emission spectroscopy in 13 evaluable patients. In a first group of 10 patients 100 mg BSH/kg bodyweight (BW) were administered; a second group of 3 patients received 22.9 mg BSH/kg BW. The toxicity due to BSH was evaluated.

Results: The average boron concentration in the tumor was 19.9 +/- 9.1 ppm (1 standard deviation (SD)) in the high dose group and 9.8 +/- 3.3 ppm in the low dose group, the tumor/blood ratios were 0.6 +/- 0.2 and 0.9 +/- 0.2, respectively. The highest boron uptake has been detected in the dura, very low uptake was found in the bone, the cerebro-spinal fluid and especially in the brain (brain/blood ratio 0.2 +/- 0.02 and 0.4 +/- 0.2). No toxicity was detected except flush-like symptoms in 2 cases during a BSH infusion at a much higher speed than prescribed.

Conclusion: BSH proved to be safe for clinical application at a dose of 100 mg BSH/kg infused and at a dose rate of 1 mg/kg/min. The study underlines the importance of a further investigation of BSH uptake in order to obtain enough data for significant statistical analysis. The boron concentration in blood seems to be a quite reliable parameter to predict the boron concentration in other tissues.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Boron / adverse effects
  • Boron / analysis*
  • Boron / pharmacokinetics*
  • Boron Compounds / administration & dosage
  • Boron Compounds / adverse effects
  • Boron Neutron Capture Therapy* / adverse effects
  • Brain Neoplasms / radiotherapy*
  • Dose-Response Relationship, Radiation
  • Female
  • Glioblastoma / radiotherapy*
  • Humans
  • Male
  • Middle Aged
  • Radiotherapy Dosage
  • Tissue Distribution

Substances

  • Boron Compounds
  • Boron