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 & 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 h), 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 h), 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.

Imaging a photodynamic therapy photosensitizerin vivowith a time-gated fluorescence tomography system

“…[1][2][3] With high tumor avidity, the chlorin-based compound 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) has been shown to be a potential photosenstizer for imaging and treatment. 4 Recent HPPH-oriented laboratory research and early-phase clinical studies at Roswell Park Cancer Institute (RPCI) have demonstrated that HPPH-mediated PDT is an effective treatment option for superficial cancers such as skin and head and neck lesions in the oral cavity. [4][5][6][7][8] The efficacy of PDT is largely dependent on the spatial distribution and temporal changes of the photosensitizer.…”

Can Nanotechnology Shine a New Light on Antimicrobial Photodynamic Therapies?

“…The interaction of molecular oxygen in its ground triplet state ( 3 O 2 ) with 3 PS* generates a more reactive form of oxygen, i.e., singlet oxygen ( 1 O 2 ). This nonradical species is highly reactive toward electron-rich substrates such as aromatic rings, amines, and thioesters [8]. The contribution of both Type I and Type II reactions to cell death depends on several factors including, among others, the PS itself, the subcellular localization, the substrate, and molecular oxygen concentration within the target cells.…”

Photodynamic Therapy

“…Since Dougherty [8] in the 1970s began clinical trials for photodynamic destruction of cutaneous and subcutaneous malignancies, PDT has been used to treat esophageal [9], laryngeal, endobronchial, gastrointestinal, genitourinary, nervous, head and neck [10], oral leucoplakia, and skin malignancies [11].…”

“…It has been described that tumor destruction of PDT is connected with indirect effects of PDT: blood vessel occlusion within vascularized tumors. These effects demonstrated [9] that PDT induces apoptosis and vascular endothelial damage [13,14]. It has also been mediated by the release of prostaglandin E2 (PGE2) and cytokines (IL-2, IL-1, TNF).…”