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 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.
Busse
Paul M
PM
Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. pbusse@caregroup.harvard.edu
Harling
Otto K
OK
Palmer
Matthew R
MR
Kiger
W S
WS
Kaplan
Jody
J
Kaplan
Irving
I
Chuang
Cynthia F
CF
Goorley
J Tim
JT
Riley
Kent J
KJ
Newton
Thomas H
TH
Santa Cruz
Gustavo A
GA
Lu
Xing-Qi
XQ
Zamenhof
Robert G
RG
D000328:Adult; D000368:Aged; D001895:Boron / Q000097:blood / Q000493:pharmacokinetics*; D016754:Boron Neutron Capture Therapy / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000532:radiotherapy* / Q000556:secondary; D004307:Dose-Response Relationship, Radiation; D005909:Glioblastoma / Q000532:radiotherapy*; D006801:Humans; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000532:radiotherapy*; D008875:Middle Aged; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D016896:Treatment Outcome
D001895:Boron