Abstract
BackgroundTreatment failure at the primary site after chemoradiotherapy is a major problem in achieving a complete response. Photodynamic therapy (PDT) with porfimer sodium (Photofrin®) has some problems such as the requirement for shielding from light for several weeks and a high incidence of skin phototoxicity. PDT with talaporfin sodium (Laserphyrin) is less toxic and is expected to have a better effect compared with Photofrin PDT. However, Laserphyrin PDT is not approved for use in the esophagus. In this preclinical study, we investigated tissue damage of the canine normal esophagus caused by photoactivation with Laserphyrin.Methodology/Principal FindingsDiode laser irradiation was performed at 60 min after administration. An area 5 cm oral to the esophagogastric junction was irradiated at 25 J/cm2, 50 J/cm2, and 100 J/cm2 using a three-step escalation. The irradiated areas were evaluated endoscopically on postirradiation days 1 and 7, and were subjected to histological examination after autopsy. The areas injured by photoactivation were 52 mm2, 498 mm2, and 831 mm2 after irradiation at 25 J/cm2, 50 J/cm2, and 100 J/cm2, respectively. Tissue injury was observed in the muscle layer or even deeper at any irradiation level and became more severe as the irradiation dose increased. At 100 J/cm2 both inflammatory changes and necrosis were seen histologically in extra-adventitial tissue.Conclusions/SignificanceTo minimize injury of the normal esophagus by photoactivation with Laserphyrin, diode laser irradiation at 25 J/cm2 appears to be safe. For human application, it would be desirable to investigate the optimal laser dose starting from this level.
Highlights
Photodynamic therapy (PDT) is a local endoscopic treatment using a photochemical reaction induced by an oncotropic photosensitizer and a laser [1,2,3]
PDT is useful for treating superficial esophageal cancer, preventing the development of adenocarcinoma from high-grade dysplasia in the Barrett’s esophagus, and alleviating stenosis caused by advanced esophageal cancer [4,5,6]
Laserphyrin PDT, a second-generation PDT, induces a phototoxic effect when the timing of photoactivation is associated with the peak plasma level of the photosensitizer
Summary
Photodynamic therapy (PDT) is a local endoscopic treatment using a photochemical reaction induced by an oncotropic photosensitizer and a laser [1,2,3]. We have reported on the benefits of PDT as a salvage treatment for local residues and recurrence after definitive chemoradiotherapy (CRT) for esophageal cancer. Salvage PDT has excellent treatment outcomes for local residues and recurrence after CRT with a 59.5–62.0% complete response rate and a 5-year overall survival of 36.1% without severe adverse events [7,8]. Photodynamic therapy (PDT) with porfimer sodium (PhotofrinH) has some problems such as the requirement for shielding from light for several weeks and a high incidence of skin phototoxicity. Laserphyrin PDT is not approved for use in the esophagus. We investigated tissue damage of the canine normal esophagus caused by photoactivation with Laserphyrin
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