RESUMEN
OBJECTIVE: To evaluate the potent photosensitizer m-tetra (hydroxyphenyl) chlorin (m-THPC) by using rabbits with cottontail rabbit papillomavirus-induced tumors and the canine larynx as model systems. DESIGN: Nonrandomized control trial. SETTING: Division of ear, nose, and throat research at a tertiary care teaching hospital. MATERIALS: Rabbits were used for relative retention ratio studies and tissue tolerance tests. Studies on the swelling of normal tissues in the larynx after photoactivation were done with canines. INTERVENTION: Animals were injected with 0.3 mg/kg of m-THPC. At varying intervals, tissues were exposed to 652 nm of light. OUTCOME MEASURES: Outcome measures consisted of four elements: (1) decay of plasma concentration over time, (2) interval to and duration of maximal ratio between drug concentration in normal tissue and tumor, (3) maximal permissible light exposure to normal tissue (skin and laryngeal mucosa) at an optimal interval, and (4) efficacy--number of tumors with partial and complete response. RESULTS: The largest papilloma to skin ratio (10:1) occurred 4 to 8 days after drug injection. The rabbit skin damage threshold was 40 to 60 J/cm2 at 6 days. The canine laryngeal edema and erythema thresholds were 50 to 70 J. A 75% cure rate of papillomas was achieved with tumors that were less than 100 mm2 in area at light doses that ranged from 25 to 75 J/cm2. CONCLUSIONS: m-THPC shows efficacy in treating papilloma virus-induced tumors. We present a protocol for rapid optimization of the factors required for tumor destruction with minimal normal tissue damage, thus permitting determination of an optimal therapeutic protocol for any photosensitizer.
Asunto(s)
Antineoplásicos/uso terapéutico , Papillomavirus del Conejo de Rabo Blanco , Neoplasias Laríngeas/tratamiento farmacológico , Mesoporfirinas/uso terapéutico , Infecciones por Papillomavirus/tratamiento farmacológico , Fotoquimioterapia/métodos , Neoplasias Cutáneas/tratamiento farmacológico , Infecciones Tumorales por Virus/tratamiento farmacológico , Animales , Antineoplásicos/sangre , Antineoplásicos/farmacocinética , Protocolos Clínicos , Modelos Animales de Enfermedad , Perros , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Monitoreo de Drogas , Neoplasias Laríngeas/sangre , Mesoporfirinas/sangre , Mesoporfirinas/farmacocinética , Infecciones por Papillomavirus/sangre , Fotoquimioterapia/efectos adversos , Conejos , Neoplasias Cutáneas/sangre , Factores de Tiempo , Infecciones Tumorales por Virus/sangreRESUMEN
Whether cell death in carcinoma of the larynx during photodynamic therapy is due to singlet oxygen formation or mild hyperthermia is not resolved. When various experimental tumors were previously heated within the range of 41 degrees C to 43 degrees C, selective destruction was found. A canine model was used by placing a thermocouple probe into the vocal cord and then varying the total energy (10 to 150 J/cm2), using a 630-nm dye laser; a temperature rise of only 0.5 degrees C to 2.1 degrees C was found. Thus, the thermal effects generated within the larynx (final temperature, 34.9 degrees C to 37.1 degrees C) should be insufficient to act alone in achieving a therapeutic response in either tumor tissue or destruction of normal epithelium.