Photodynamic therapy (PDT) using HPPH for the treatment of precancerous lesions associated with Barrett's esophagus.

Abstract

BACKGROUND AND OBJECTIVES:

Photodynamic therapy (PDT) with porfimer sodium, FDA approved to treat premalignant lesions in Barrett's esophagus, causes photosensitivity for 6-8 weeks. HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a) shows minimal photosensitization of short duration and promising efficacy in preclinical studies. Here we explore toxicity and optimal drug and light dose with endoscopic HPPH-PDT. We also want to know the efficacy of one time treatment with HPPH-PDT.

STUDY DESIGN/MATERIALS AND METHODS:

Two nonrandomized dose escalation studies were performed (18 patients each) with biopsy-proven high grade dysplasia or early intramucosal adenocarcinoma of esophagus. HPPH doses ranged from 3 to 6 mg/m2 . At 24 or 48 hours after HPPH administration the lesions received one endoscopic exposure to 150, 175, or 200 J/cm of 665 nm light.

RESULTS:

Most patients experienced mild to moderate chest pain requiring symptomatic treatment only. Six patients experienced grade 3 and 4 adverse events (16.6%). Three esophageal strictures were treated with dilatation. No clear pattern of dose dependence of toxicities emerged. In the drug dose ranging study (light dose of 150 J/cm at 48 hours), 3 and 4 mg/m2 of HPPH emerged as most effective. In the light dose ranging study (3 or 4 mg/m2 HPPH, light at 24 hours), complete response rates (disappearance of high grade dysplasia and early carcinoma) of 72% were achieved at 1 year, with all patients treated with 3 mg/m2 HPPH plus 175 J/cm and 4 mg/m2 HPPH plus 150 J/cm showing complete responses at 1 year.

CONCLUSIONS:

HPPH-PDT for precancerous lesions in Barrett's esophagus appears to be safe and showing promising efficacy. Further clinical studies are required to establish the use of HPPH-PDT.

• Authors: Hector R Nava, Shyam S Allamaneni, Thomas J Dougherty, Michele T Cooper, Wei Tan, Gregory Wilding, Barbara W Henderson
• Journal: Lasers in surgery and medicine (Lasers Surg Med) Vol. 43 Issue 7 Pg. 705-12 (Sep 2011) ISSN: 1096-9101 [Electronic] United States
• PMID: 22057498 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Wiley-Liss, Inc.

Chemical References

• Photosensitizing Agents
• Chlorophyll
• 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a

Topics

• Adenocarcinoma (drug therapy)
• Aged
• Aged, 80 and over
• Barrett Esophagus (complications)
• Chlorophyll (analogs & derivatives, therapeutic use)
• Dose-Response Relationship, Drug
• Dose-Response Relationship, Radiation
• Drug Administration Schedule
• Esophageal Neoplasms (drug therapy)
• Esophagoscopy
• Female
• Humans
• Infusions, Intravenous
• Male
• Middle Aged
• Photochemotherapy
• Photosensitizing Agents (therapeutic use)
• Precancerous Conditions (drug therapy)
• Treatment Outcome