RESUMO
BACKGROUND: Photodynamic therapy (PDT) has been successfully applied in clinical settings to destroy neoplasms, but the efficacy of such a treatment is dependent on the type of neoplasm and the photosynthesizer used. Here, we perform a clinical assessment of PDT for skin metastases of pigmented melanoma using chlorin e(6). STUDY DESIGN/MATERIALS AND METHODS: PDT with chlorin e(6) photosensitizer was administered to 14 patients with skin metastases from melanoma (10 females, four males, mean age 49.6 years). Chlorin e(6) at a dose of 5 mg/kg of patient's weight was intravenously injected. The treatment course consisted of two courses of PDT exposure 1 h after intravenous chlorin e(6) injection and 24 h post-injection. The light energy density for each skin tumor was 80-120 J/cm(2) per treatment, with a light power density of 250-300 mW/cm(2). RESULTS: All skin melanoma metastases that received PDT showed complete regression with no recurrence during the study period. The complete response of all skin metastases from melanoma occurred in eight cases after one PDT treatment. In the remaining six individuals, tumors required multiple PDT courses prior to complete regression. No cases of photodermatitis were registered. The Karnofsky performance scale score of the patients with skin metastases from melanoma showed no significant difference before and after PDT. No patients had significant changes in blood cell counts that would indicate chlorin e(6) systemic toxic effect. Blood chemistry and urinalysis did not show any evidence of chlorin e(6) renal and hepatic injury. CONCLUSIONS: PDT with chlorin e(6) for skin metastases from melanoma is effective and well tolerated. Further clinical investigation of PDT with chlorin e(6) is warranted.
Assuntos
Melanoma/tratamento farmacológico , Melanoma/secundário , Fotoquimioterapia , Porfirinas/uso terapêutico , Radiossensibilizantes/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/secundário , Clorofilídeos , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Fotoquimioterapia/efeitos adversos , Porfirinas/efeitos adversos , Radiossensibilizantes/efeitos adversos , Neoplasias Cutâneas/patologiaRESUMO
AIM: To evaluate the influence of pH on accumulation and photocytotoxicity of the novel tricarbocyanine indolenine dye covalently bound with glucose (TICS). METHODS: For in vitro experiments, cultured HeLa cells were incubated with TICS at pH 7.1, 6.5 or 6.2 and then scored for dye uptake, viability and sensitivity to laser (740 nm) irradiation. In vivo TICS was injected to rats with implanted subcutaneously SM-1 tumor and then dye accumulation and tumor necrosis depth after laser irradiation were defined. RESULTS: Reduction of medium pH in vitro was shown to increase in cellular TICS contents and to enhance as its "dark" cytotoxicity, and photocytotoxicity. The ratio of "dark" cytotoxicity to photocytotoxicity parameters increased 2-fold with decreasing pH value. In vivo infusion of glucose (10 g/kg) to rats resulted in improved selectivity of TICS accumulation and increase in tumor necrosis depth after laser irradiation. CONCLUSION: pH reduction of tumor cells environment improves efficacy of photodynamic treatment with TICS.