Phase I drug and light dose-escalation trial of motexafin lutetium and far red light activation (phototherapy) in subjects with coronary artery disease undergoing percutaneous coronary intervention and stent deployment: procedural and long-term results.
BACKGROUND
Motexafin lutetium (MLu; Antrin) is a photosensitizer that is taken up by atherosclerotic plaque and concentrated within macrophages and vascular smooth muscle cells. After photoactivation with far red light, MLu facilitates production of cytotoxic oxygen radicals that mediate apoptosis. We assessed the safety and tolerability of phototherapy (PT) with MLu in patients undergoing percutaneous coronary intervention with stent deployment.


RESULTS
An open-label, phase I, drug and light dose-escalation clinical trial of MLu PT enrolled 80 patients undergoing de novo coronary stent deployment. MLu was administered to 79 patients by intravenous infusion 18 to 24 hours before procedure, and photoactivation was performed after balloon predilatation and before stent deployment. Clinical evaluation, serial quantitative angiography, and intravascular ultrasound were performed periprocedurally and at 6 months follow-up. MLu PT was well tolerated without serious dose-limiting toxicities, and side effects (paresthesia and rash) were minor. No adverse angiographic outcomes were attributed to phototherapy.


CONCLUSIONS
This study demonstrates that coronary MLu PT seems safe, and the maximum well-tolerated MLu dose and range of tolerated light doses were identified. These data can be used in phase II efficacy trials of MLu PT for the treatment of coronary atherosclerosis or vulnerable plaque.
Kereiakes
Dean J
DJ
The Lindner Center for Research & Education, 2123 Auburn Ave, Suite 424, Cincinnati, Ohio 45219, USA.
Szyniszewski
Arthur M
AM
Wahr
Dennis
D
Herrmann
Howard C
HC
Simon
Daniel I
DI
Rogers
Campbell
C
Kramer
Paul
P
Shear
Wendy
W
Yeung
Alan C
AC
Shunk
Kendrick A
KA
Chou
Tony M
TM
Popma
Jeffrey
J
Fitzgerald
Peter
P
Carroll
Tanya E
TE
Forer
David
D
Adelman
Daniel C
DC
D000328:Adult; D015906:Angioplasty, Balloon, Coronary; D003131:Combined Modality Therapy; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000601:surgery / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008665:Metalloporphyrins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D010778:Photochemotherapy / Q000009:adverse effects; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015607:Stents; D016896:Treatment Outcome
D008665:Metalloporphyrins; D017319:Photosensitizing Agents; C102825:motexafin lutetium