Comparison of high- vs low-dose 5-aminolevulinic acid for photodynamic therapy of Barrett's esophagus

Background: Barrett's esophagus is the major risk factor for esophageal adenocarcinoma, the incidence of which is increasing rapidly in the Western world. Aminolevulinic acid for photodynamic therapy (ALA-PDT) is effective in the treatment of Barrett's esophagus, but controversy exists regarding optimum ALA dosage. The aim of this study was to establish the optimum dosage regime for ALA-PDT for Barrett's esophagus. Methods: Twenty-five patients with Barrett's esophagus were randomized to receive 30 (low-dose) or 60 (high-dose) mg/kg oral ALA at 4 or 6 h or 30 mg/kg in two fractions 4 and 6 h before PDT. PDT was standardized using red (635 nm) light. Biopsy specimens were taken for protoporphyrin IX (PpIX) quantification. Endoscopy was repeated 4 weeks later. Results: All patients showed a macroscopic response, with squamous re-epithelialization. This response was greatest in the 30 mg/kg and fractionated ALA groups. There was no significant difference in response between dosing 4 or 6 h prior to PDT. Tissue levels of PpIX were similar for all dosage groups and were not predictive of clinical response. Side effects were more common with the higher dose of ALA. Conclusion: Low-dose ALA-PDT appears to be a safe protocol for the ablation of Barrett's esophagus.