Phase I and pharmacokinetic study of photodynamic therapy for high-grade gliomas using a novel boronated porphyrin.
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.
Rosenthal
M A
MA
Centre for Developmental Cancer Therapeutics, Parkville, Australia. mark.rosenthal@ludwig.edu.au
Kavar
B
B
Hill
J S
JS
Morgan
D J
DJ
Nation
R L
RL
Stylli
S S
SS
Basser
R L
RL
Uren
S
S
Geldard
H
H
Green
M D
MD
Kahl
S B
SB
Kaye
A H
AH
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
D011524:Protoporphyrins; D011838:Radiation-Sensitizing Agents; C073289:boron protoporphyrin