title: L-boronophenylalanine-mediated boron neutron capture therapy for malignant glioma progressing after external beam radiation therapy: a Phase I study.
abstract: OBJECTIVE
  To investigate the safety of boronophenylalanine-mediated boron neutron capture therapy (BNCT) in the treatment of malignant gliomas that progress after surgery and conventional external beam radiation therapy.
  
  
  METHODS
  Adult patients who had histologically confirmed malignant glioma that had progressed after surgery and external beam radiotherapy were eligible for this Phase I study, provided that >6 months had elapsed from the last date of radiation therapy. The first 10 patients received a fixed dose, 290 mg/kg, of L-boronophenylalanine-fructose (L-BPA-F) as a 2-hour infusion before neutron irradiation, and the remaining patients were treated with escalating doses of L-BPA-F, either 350 mg/kg, 400 mg/kg, or 450 mg/kg, using 3 patients on each dose level. Adverse effects were assessed using National Cancer Institute Common Toxicity Criteria version 2.0.
  
  
  RESULTS
  Twenty-two patients entered the study. Twenty subjects had glioblastoma, and 2 patients had anaplastic astrocytoma, and the median cumulative dose of prior external beam radiotherapy was 59.4 Gy. The maximally tolerated L-BPA-F dose was reached at the 450 mg/kg level, where 4 of 6 patients treated had a grade 3 adverse event. Patients who were given >290 mg/kg of L-BPA-F received a higher estimated average planning target volume dose than those who received 290 mg/kg (median, 36 vs. 31 Gy [W, i.e., a weighted dose]; p = 0.018). The median survival time following BNCT was 7 months.
  
  
  CONCLUSIONS
  BNCT administered with an l-BPA-F dose of up to 400 mg/kg as a 2-hour infusion is feasible in the treatment of malignant gliomas that recur after conventional radiation therapy.
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Leena
authors.initials: L
authors.lastname: Kankaanranta
authors.forename: Tiina
authors.initials: T
authors.lastname: Seppälä
authors.forename: Hanna
authors.initials: H
authors.lastname: Koivunoro
authors.forename: Petteri
authors.initials: P
authors.lastname: Välimäki
authors.forename: Annette
authors.initials: A
authors.lastname: Beule
authors.forename: Juhani
authors.initials: J
authors.lastname: Collan
authors.forename: Mika
authors.initials: M
authors.lastname: Kortesniemi
authors.forename: Jouni
authors.initials: J
authors.lastname: Uusi-Simola
authors.forename: Petri
authors.initials: P
authors.lastname: Kotiluoto
authors.forename: Iiro
authors.initials: I
authors.lastname: Auterinen
authors.forename: Tom
authors.initials: T
authors.lastname: Serèn
authors.forename: Anders
authors.initials: A
authors.lastname: Paetau
authors.forename: Kauko
authors.initials: K
authors.lastname: Saarilahti
authors.forename: Sauli
authors.initials: S
authors.lastname: Savolainen
authors.forename: Heikki
authors.initials: H
authors.lastname: Joensuu
mesh_terms: D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D001896:Boron Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016754:Boron Neutron Capture Therapy / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D018450:Disease Progression; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005909:Glioblastoma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D055815:Young Adult
chemical_list: C089739:4-boronophenylalanine-fructose; D001896:Boron Compounds; D011838:Radiation-Sensitizing Agents; D005632:Fructose