title: Phase I and pharmacokinetic study of photodynamic therapy for high-grade gliomas using a novel boronated porphyrin.
abstract: OBJECTIVE
  To determine the recommended dose, toxicity profile, and pharmacokinetics of a novel boronated porphyrin (BOPP) for photodynamic therapy (PDT) of intracranial tumors.
  
  
  METHODS
  BOPP was administered alone in increasing doses (0.25, 0.5, 1.0, 2.0, 4.0, or 8.0 mg/kg) preoperatively in patients with intracranial tumors undergoing postresection PDT until dose-limiting toxicity (DLT) was observed.
  
  
  RESULTS
  Twenty-nine assessable patients with intracranial tumors received BOPP intravenously 24 hours before surgery. The recommended dose was 4 mg/kg. Dose escalation was limited by thrombocytopenia. The most common nonhematologic toxicity was skin photosensitivity. Pharmacokinetic parameters showed increased area under the plasma concentration-time curve and maximum concentration with increased dose. Tumor BOPP concentrations also increased with increased dose.
  
  
  CONCLUSIONS
  BOPP at a dose of 4 mg/kg was well tolerated. DLT was thrombocytopenia, and photosensitivity was the only other toxicity of note. The efficacy of PDT using BOPP requires further exploration.
authors.affiliation: Centre for Developmental Cancer Therapeutics, Parkville, Australia. mark.rosenthal@ludwig.edu.au
authors.forename: M A
authors.initials: MA
authors.lastname: Rosenthal
authors.forename: B
authors.initials: B
authors.lastname: Kavar
authors.forename: J S
authors.initials: JS
authors.lastname: Hill
authors.forename: D J
authors.initials: DJ
authors.lastname: Morgan
authors.forename: R L
authors.initials: RL
authors.lastname: Nation
authors.forename: S S
authors.initials: SS
authors.lastname: Stylli
authors.forename: R L
authors.initials: RL
authors.lastname: Basser
authors.forename: S
authors.initials: S
authors.lastname: Uren
authors.forename: H
authors.initials: H
authors.lastname: Geldard
authors.forename: M D
authors.initials: MD
authors.lastname: Green
authors.forename: S B
authors.initials: SB
authors.lastname: Kahl
authors.forename: A H
authors.initials: AH
authors.lastname: Kaye
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001932:Brain Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010778:Photochemotherapy; D011524:Protoporphyrins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution
chemical_list: D011524:Protoporphyrins; D011838:Radiation-Sensitizing Agents; C073289:boron protoporphyrin