RESUMEN
BACKGROUND: Gallbladder cancer (GBC) has a poor prognosis. Chemotherapy is traditionally considered to be ineffective. The goal of the current study was to evaluate the efficacy of infusional 5-fluorouracil (5-FU) and cisplatinum (CDDP) in patients with inoperable GBC. MATERIALS AND METHODS: A total of 65 patients with inoperable GBC received palliative chemotherapy with CDDP and 5-FU. All the patients had clinically measurable disease as well as adequate bone marrow, hepatic, and renal function. Response was assessed after three cycles of chemotherapy. RESULTS: A total of 19 patients had locally advanced unresectable cancer and 46 patients had metastatic cancer. There were 39 females and 26 males, with a median age of 50 years. A total of 212 chemotherapy cycles were administered to the patients. Response evaluation after three cycles of chemotherapy revealed complete response in five patients [7.69%; 95% confidence interval (95% CI): 2.87-16.22], partial response in 17 patients (26.15%; 95% CI: 16.57-37.81), stabilization of disease in 9 patients (13.85%; 95% CI: 6.96-23.88), and progression in 21 patients (32.30%; 95% CI: 21.80-44.35). At 6 months 44.6% patients were alive and 18.5% patients were alive at 12 months. The median overall survival was 5.7 months and the median time to disease progression was 3.1 months. This chemotherapy combination was well tolerated. There were no chemotherapy-related deaths. CONCLUSIONS: Infusion chemotherapy with CDDP and 5-FU appears to have a fair amount of activity in patients of inoperable GBC, with acceptable toxicity. Tumor shrinkage following treatment with this regimen enabled surgical resection in two patients. We believe that this promising combination must be tested against gemcitabine-based combinations in patients with inoperable GBC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/administración & dosificación , Fluorouracilo/administración & dosificación , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/patología , Adulto , Anciano , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Estudios Prospectivos , Resultado del Tratamiento , GemcitabinaRESUMEN
Homocysteine has been recently recognised as a risk factor for atherosclerotic vascular disease. Numerous studies have studied adverse influence of homocysteine on endothelial cells, vascular smooth muscle cells, connective tissue, interactions with plasma lipoproteins, clotting factors and platelets. It has been suggested that endothelial damage is mediated by hydrogen peroxide, a by-product of auto-oxidation of homocysteine. Human studies have shown that high levels of homocysteine are associated with impaired endothelial dependent vasodilatation in healthy subjects indicating that the bio-availability of nitric oxide (NO) is decreased in those with hyper-homocysteinemia. Homocysteine thialactone (a by-product of homocysteine auto-oxidation) combines with native LDL to form oxidized LDL which is taken up by intimal macrophages to form foam cells which is the beginning of atheromatous plaques. Homocysteine has also influence on proliferation of vascular smooth muscle cells and collagen deposition in atheromatous plaque. In addition several retrospective and prospective studies have shown that hyperhomocysteinaemia is associated with atheromatous and vascular events. Observations in 80 clinical and epidemiological studies have indicated that hyper-homocysteinaemia is a risk factor for atherosclerotic disease. However there are some studies which conclude that homocysteine is not a major risk factor for coronary heart disease.