Clinical Trial of Photodynamic Therapy With Meso-Tetra (Hydroxyphenyl) Chlorin for Respiratory Papillomatosis

University of Texas at Dallas, Richardson, Texas, United States
Archives of Otolaryngology - Head and Neck Surgery (Impact Factor: 2.33). 03/2005; 131(2):99-105. DOI: 10.1001/archotol.131.2.99
Source: PubMed


To determine the efficacy of photodynamic therapy (PDT) with meso-tetra (hydroxyphenyl) chlorin (m-THPC) photosensitizer for recurrent respiratory papillomatosis.
Parallel-arm, randomized trial of patients requiring surgery at least 3 times yearly with single PDT 6 or 18 months after enrollment and 12-month follow-up. Disease extent was scored and papillomas were removed during direct endoscopy every 3 months after enrollment.
Tertiary medical centers.
Of 23 patients aged 4 to 60 years enrolled in the study, 15 patients, plus 2 in the late group without PDT owing to airway risk, completed the study. Six patients withdrew voluntarily after PDT.
Intravenous administration of m-THPC 6 days before direct endoscopic PDT with 80 to 100 J of light for adults and 60 to 80 J for children.
Difference in severity scores between the early and late groups and between pre- and post-PDT scores for all patients. Secondary measures were the associations between baseline characteristics and response and changes in immune response and the prevalence of latent viral DNA.
There were significant differences between groups, with marked improvement in laryngeal disease across time after PDT (P = .006). Five of 15 patients were in remission 12 to 15 months after treatment, but there was recurrence of disease after 3 to 5 years. Tracheal disease was not responsive to PDT. No change occurred in the prevalence of latent human papillomavirus DNA. The immune response to virus improved with clinical response.
Use of m-THPC PDT reduces the severity of laryngeal papillomas, possibly through an improved immune response. Failure to maintain remission with time suggests that this is not an optimal treatment.

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    • "yngeal papillomas, but failed to maintain remission. Five of the 15 patients were in remission 12–15 months after treatment, but had disease reoccurrence after 3–5 years. Out of the 23 patients (ages 4–60 years) that initially began this study, only 15 people were available for follow-up. Shikowitz concluded that mTHC was not an optimal treatment.(Shikowitz et al. 2005)"
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    ABSTRACT: In this article, we describe the treatment of long standing juvenile-onset recurrent respiratory papillomatosis (JORRP) with eventual transformation to carcinoma in a patient who lived to the age of 73. Treatment modalities consisted of bronchoscopy and local excision initially. Later, YAG and CO2 laser debulking were used. Radiotherapy, chemotherapy with carboplatin (300 mg/m2) and 5-FU (600 mg/m2), oral methotrexate (5-7.5 mg/week), pegylated Interferon, indole-3-carbamide, and intralesional cidofovir were also utilized in the treatment of this patient. Except for methotrexate, each of the treatment regimens used in this patient, initially decreased growth of the papillomas and improved symptoms experienced by the patient. Interestingly, we found that this patient's long standing JORRP initially responded to a chemotherapy regimen of 4 cycles of carboplatin (300 mg/m2) and 5-FU (600 mg/m2) as well. Ultimately, the disease became resistant to all forms of treatment and progressed. The patient eventually succumbed to the disease after an approximate 77 year course.
    Clinical Medicine: Oncology 07/2008; 2:481-6.
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    • "Foscan® (meta-tetrahydroxyphenylchlorin), a second-generation photosensitiser has been granted European approval for palliative treatment of advanced head and neck cancers. The efficacy of Foscan®–PDT in the treatment of early squamous cell carcinoma (Hopper et al, 2004; Lou et al, 2004) and other malignancies has also been recently reported (Campbell et al, 2004; Lovat et al, 2005; Shikowitz et al, 2005). Endoplasmic reticulum and Golgi apparatus have been demonstrated as preferential sites of Foscan® accumulation in cultured tumour cells after 3-h incubation (Teiten et al, 2003a) leading to primary photodamage of these organelles upon irradiation (Teiten et al, 2003b). "
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    ABSTRACT: The present study investigates the relationship between the subcellular localisation of Foscan and intrinsic apoptotic pathway post Foscan-based photodynamic therapy (PDT). With this purpose, mammary carcinoma MCF-7 cells were incubated with Foscan for 3 or 24 h and then subjected to equitoxic light doses. Fluorescence microscopy revealed very good Foscan co-localization to endoplasmic reticulum (ER) and Golgi apparatus after 3 h incubation with MCF-7 cells. Progressive increase in incubation time shows leakage of Foscan from Golgi apparatus. Twenty-four hours incubation yielded a fluence-dependent enhanced induction of the ER-resident glucose-regulated protein 78 (Bip/GRP78), along with a weak mitochondrial damage, thus underscoring the ER as the main site of photodamage after prolonged incubation. Analysis of events implicated in apoptotic pathway after 24 h incubation demonstrated photodamage to Bcl-2 protein in total cellular extract, but not in the mitochondrial fraction. We further determined an increase in caspases-7 and -6 activation, which was strongly related to the expression of GRP78. The above findings demonstrate that Foscan localisation in ER improves the photoactivation of the caspase-7 apoptotic pathway, which is poorly related to mitochondrial damage.
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