title: Photodynamic therapy (PDT) using HPPH for the treatment of precancerous lesions associated with Barrett's esophagus.
abstract: OBJECTIVE
  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.
  
  
  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: Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors: Hector R
authors: HR
authors: Nava
authors: Shyam S
authors: SS
authors: Allamaneni
authors: Thomas J
authors: TJ
authors: Dougherty
authors: Michele T
authors: MT
authors: Cooper
authors: Wei
authors: W
authors: Tan
authors: Gregory
authors: G
authors: Wilding
authors: Barbara W
authors: BW
authors: Henderson
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000150:complications*; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D004945:Esophagoscopy; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011230:Precancerous Conditions / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D017319:Photosensitizing Agents; D002734:Chlorophyll; C083998:2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a