RESUMO
Current treatment strategies for high-grade gliomas are inadequate with high rates of disease recurrence and poor overall survival. Photodynamic therapy has been extensively investigated for a variety of tumours including high-grade gliomas. We have previously described a novel boronated porphyrin (BOPP) which has highly selective uptake by tumour cells. A Phase I study documented that BOPP at a dose of 4mg/kg was well tolerated. We report here the survival data arising from this Phase I study. Overall 28 patients (pts) with high-grade gliomas were treated with BOPP photodynamic therapy with a median overall survival (OS) of 14 months (2-48+ months). Sixteen pts had glioblastoma multiforme (GBM) with a median OS of 8 months (2-38+). Of 9 pts with recurrent GBM, the median OS was 11 months (3-38+), with 56% surviving at least 12 months. In conclusion, BOPP photodynamic therapy was associated with encouraging survival particularly in the recurrent GBM setting.
Assuntos
Compostos de Boro/uso terapêutico , Deuteroporfirinas/uso terapêutico , Glioma/mortalidade , Glioma/radioterapia , Oligodendroglioma/radioterapia , Adulto , Idoso , Compostos de Boro/efeitos adversos , Terapia por Captura de Nêutron de Boro , Deuteroporfirinas/efeitos adversos , Progressão da Doença , Relação Dose-Resposta à Radiação , Feminino , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Oligodendroglioma/mortalidade , Taxa de Sobrevida , SobreviventesRESUMO
Among the most important characteristics of any therapeutic agent are efficacy and an acceptable toxicity. Prior to human use, toxicity studies are performed in both small and large animal models. Our laboratory has developed a new binary therapy agent, a boronated porphyrin (BOPP), with excellent potential efficacy. The purpose of this study is to examine the toxicology of this compound in dogs. Sixteen dogs were given 35 mg/kg of BOPP intravenously and evaluated for up to 28 days following administration. Clinical and pathologic responses were measured. BOPP was clinically well tolerated with some cases of weight loss, vomiting and mild photosensitivity. Adverse effects were limited primarily to thrombosis at the administration site in several subjects and three cases of mild, possibly transient, liver injury. Clinical pathologic tests found reversible changes in white blood cell counts and platelets, with neither change being clinically significant. The low toxicity associated with BOPP as shown in this study provides valuable evidence supporting the use of BOPP in binary therapy.
