Intralesional administration of photosensitizer in photodynamic therapy: a novel approach

Background: Photodynamic therapy (PDT) is a promising form of cancer treatment. PDT relies on light activation of a systemically administered photosensitizer which can result in significant complications such as cutaneous phototoxicity and esophageal strictures. Aim: To assess the effectiveness and systemic adverse effects of intralesional administration of a photosensitizer in PDT of a patient with esophageal carcinoma. Methods: A 76 y/o white female was evaluated for intralesional PDT regarding adenocarcinoma (T2N0M0) arising on a background of specialized Barrett's mucosa. Her history is complicated by Child's B cirrhosis with portal hypertension s/p TIPS procedure and significant thrombocytopenia predisposing her to high-risk surgery. Chemotherapy and radiation therapy were contra-indicated. PDT was performed 6 months previously using intravenously administered photosensitizer which resulted in nausea and vomiting precipitating an episode of hepatic coma. The patient also developed cutaneous phototoxicity. Because of tumor persistence, intralesional PDT was offered as an alternative therapy in the hope of eradicating the tumor and avoiding systemic toxicity. Our recent animal studies demonstrated the effectiveness of local administration of hematoporphyrin derivative (HpD) in PDT. From these studies, we determined that maximal tissue damage occurred when phototherapy is conducted within 6-24 hrs after local administration of HpD (p<0.05). No systemic phototoxicity was noted. Ten mls of porfimer sodium at a concentration of 2 mg/ml was injected intralesionally into the patient's esophageal tumor using a 4 mm sclerotherapy needle. Six hrs post photosensitizer injection, phototherapy was applied at a dose of 300 J/cm fiber with a 2.5 cm diffusing fiber at a power of 400 mW at 630 nm. Endoscopic assessment was performed the following day. Laser-induced fluorescence (LIF) was also performed 24 hrs post intralesional injection to assess systemic drug concentration. Results: Post PDT endoscopy revealed significant necrosis of the treated area. The tissue damage was limited to the tumor bed sparing necrosis of the contralateral wall. LIF showed no systemic distribution of the photosensitizer. In addition, the patient demonstrated no adverse effects such as nausea, vomiting, or cutaneous phototoxicity. Conclusions: Intralesional PDT seems to be effective in the management of localized lesions. Its primary advantages over systemic photosensitizer administration include minimizing skin phototoxicity and maximizing local tissue destruction. The latter expectedly will result in lesser circumferential damage that predisposes to stricture formation.